BACKGROUND AND OBJECTIVES: The objectives of this study is to treat the cases of fibromyositic rheumatisms untreatable with other therapies. The authors chose defocalized laser beams because some experimental studies had showed their analgesic and anti-phlogistic effects on experimental phlogosis. Since 1980 non-surgical laser effects were often noncomparable because of the lack of common treatment protocols. This summarizes fifteen years of clinical observations as to the purpose of identifying some indications on laser treatment of defined pathologies included in fibromyositic rheumatism. STUDY DESIGN/MATERIALS AND METHODS: 846 patients with different types of fibromyositic rheumatisms were submitted to defocalized laser therapy from 1980 to 1995. Criteria for selection included age, sex, and pathological pictures. Control groups were used to compare results with those of traditional methods. Diodes and CO2 lasers were employed, to exploit the photothermic and photochemical effects of the laser radiations to the fullest extent. RESULTS: On the whole, results were positive in comparison with other methods both as regards recovery time and persistence of results. Results were evaluated on the basis of subjective (such as local pain) and objective (hypomotility, phlogosis) criteria. CONCLUSIONS: Results obtained (approximately 2/3 of the patients benefited from the treatment) indicate that there are greater advantages in use of laser over other presently available methods. Standardalization of treatment protocols deserves further studies.

J Orofac Pain 1997;11(3):249-257, Short-term effect of glucocorticoid injection into the superficial masseter muscle of patients with chronic myalgia: a comparison between fibromyalgia and localized myalgia. Ernberg M, Hedenberg-Magnusson B, Alstergren P, Kopp S Department of Clinical Oral Physiology, Faculty of Dentistry, Karolinska Institute, Huddinge, Sweden.

The aim of this study was to investigate whether the treatment effect of intramuscular glucocorticoid injection differs between patients with fibromyalgia and those with localized myalgia of the masseter muscle concerning pain, tenderness to digital palpation, pressure pain threshold, pressure pain tolerance level, maximum voluntary occlusal force, or intramuscular temperature. Twenty-five patients with fibromyalgia and 25 patients with localized myalgia of the masseter muscle were first asked to assess their pain on a visual analogue scale; afterward, a routine clinical examination, including tenderness to digital palpation, was performed. For each patient, the pressure pain threshold, pressure pain tolerance level, and maximum voluntary occlusal force, as well as the intramuscular temperature, were recorded. Finally each patient received an injection of glucocorticoid. The examination and glucocorticoid treatment were repeated after approximately 2 weeks, and a follow-up was performed after another 5 weeks. In the fibromyalgia group, there was a reduced tenderness to digital palpation in response to the treatment. The localized myalgia group responded with a general improvement of symptoms as well as a significant reduction of pain intensity and tenderness to digital palpation. The results of this study indicate that patients with fibromyalgia and localized myalgia in many respects show a similar response to local glucocorticoid treatment.

J Orofac Pain 1997;11(3):232-241; Comorbidity between myofascial pain of the masticatory muscles and fibromyalgia. Dao TT, Reynolds WJ, Tenenbaum HC Department of Prosthodontics, Faculty of Dentistry, University of Toronto, Mount Sinai Hospital, Ontario, Canada.

This study compared myofascial pain of the masticatory muscles to fibromyalgia. Study data show that, in both myofascial pain and fibromyalgia patients, facial pain intensity and its daily pattern and effect on quality of life are very similar. This indicates that fibromyalgia should be included in the differential diagnosis for myofascial pain of the masticatory muscles. However, with the higher prevalence of neurologic and gastrointestinal symptoms, and the stronger words used to describe the affective dimension of pain, it is apparent that fibromyalgia may be a more debilitating condition than myofascial pain of the masticatory muscles. Since the intensity of facial pain was strongly and significantly correlated to the body-pain index in fibromyalgia but not in myofascial pain patients, it can be concluded that facial pain may be part of the clinical manifestations of fibromyalgia, but it is unlikely to be related to body pain in myofascial pain patients. On the other hand, while body pain is episodic in most myofascial pain patients, it is constant and more severe in the majority of fibromyalgia patients. This difference in the pain patterns suggests that body pain in fibromyalgia and myofascial pain could have different etiologies. The lack of correlation between the intensity of pain and the length of time since onset also supports the concept that myofascial pain of the masticatory muscles and fibromyalgia are unlikely to be progressive disorders.

Z Rheumatol 1997 Dec;56(6):334-341; Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain. Dohrenbusch R, Sodhi H, Lamprecht J, Genth E; Rheumaklinik und Rheumaforschungsinstitut Aachen.

We examined to what extent patients with fibromyalgia differ from painfree control subjects in the perception and processing not only of somatosensory but also of external stimuli. For this purpose the acoustic perception of 30 patients with fibromyalgia was compared with that of 36 generally pain-free age and gender matched subjects. The groups were also controlled for organic disease of pathological dysfunction of the ear and auditory nerves. Thresholds of unpleasantness and hearing thresholds were determined autiometrically for various frequencies. In addition the participants rated their experience of daily noise, vulnerability to acoustic stress, and functional and affective complaints associated with fibromyalgia. As expected the results show reduced unpleasantness thresholds for all frequencies and a nonsymptomatic hearing loss for higher frequencies. The elevated hearing threshold correlated significantly with experience of noise at the place of work, which was also elevated in the fibromyalgia group. Generalized pain had a high impact on the interaction between threshold of unpleasantness and daily noise experience. We interpret the differences in thresholds of hearing and of unpleasantness in patients with fibromyalgia as a form of either preconscious or conscious acts to protect against disturbing stimulation. Our results support the notion of a generalized disturbancy of perceptual thresholds in patients with fibromyalgia not restricted to the perception of pain.

Magnes Res 1997 Dec;10(4):329-337; Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue. Moorkens G, Manuel y Keenoy B, Vertommen J, Meludu S, Noe M, De Leeuw I; Department of Internal Medicine, University Hospital, Antwerp, Belgium.

97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38 years) with complaints of chronic fatigue (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) have been enrolled in a prospective study to evaluate the Mg status and the dietary intake of Mg. An IV loading test (performed following the Ryzen protocol) showed a Mg deficit in 44 patients. After Mg supplementation in 24 patients, the loading test showed a significant decrease (p = 0.0018) in Mg retention. Mean values of serum Mg, red blood cell Mg and magnesuria showed no significant difference between patients with or without Mg deficiency. No association was found between Mg deficiency, CFS or FM. However serum Mg level was significantly lower in the patients with spasmophilia than in the other patients.

Psychoneuroendocrinology 1997 Nov;22(8):603-614; Glucocorticoid receptors, fibromyalgia and low back pain. Lentjes EG, Griep EN, Boersma JW, Romijn FP, de Kloet ER; Department of Clinical Chemistry, University Hospital Leiden, The Netherlands.

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.

Neuroimmunomodulation 1997 May;4(3):134-153; Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Clauw DJ, Chrousos GP; Department of Medicine, Georgetown University Medical Center, Washington, D.C. 20007, USA.

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review 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.

Rev Med Interne 1997;18(10):809-813; [What is a disease]? Cathebras P; Service de medecine interne, hopital Nord, CHU de Saint-Etienne, France.

The concept of disease is more complex than it may seem. Disease is both a natural category and a social construction. Medical anthropology distinguishes between three realities under the different words defining "disease": the biological abnormalities (disease), the subjective experience of altered physical state (illness), and the process of socialization of pathological episodes (sickness). The constructivist perspective of the sociology of science shows that scientific knowledge reflects cultural beliefs and social values. A diagnosis is "constructed" in the interaction of patients and physicians, and of their respective representations of disease, in a given historical and social contex. The example of fibromyalgia has been chosen to illustrate this social construction of diagnostic categories.

J Psychosom Res 1997 Sep;43(3):293-306; Cognitive distortions of somatic experiences: revision and validation of a measure.; Moss-Morris R, Petrie KJ; Department of Psychiatry and Behavioural Science, Faculty of Medicine and Health Science, University of Auckland, New Zealand. r.moss-morris@auckland.ac.nz

The article reports on the revision of the Cognitive Errors Questionnaire (CEQ). The CEQ which was originally developed to measure cognitive distortions specific to chronic pain, has been significantly shortened and made applicable to a wider range of somatic problems. The Cognitive Errors Questionnaire-Revised (CEQ-R) contains two subscales: Somatic--distortions specific to somatic experiences; and General--distortions to everyday life events. Validation of the scale with CFS, depressed, and chronic pain groups and healthy controls confirms the CEQ-R loads onto general and somatic factors. Both subscales have high internal consistency and good test-retest reliability. The pattern of subjects' responses to the CEQ-R scores showed that the depressed group scored significantly higher on the General CEQ-R scale than the other groups, whereas the CFS and chronic pain groups scored higher than healthy controls on the Somatic CEQ-R. Somatic CEQ-R scores showed a significant decrease over the course of a pain management program, with a concomitant decrease in disability and depression scores. Further analyses showed the Somatic CEQ-R to be significantly related to self and symptom focusing, whereas the General CEQ-R was found to be significantly correlated with higher depression, lower self-esteem, and self focusing. The CEQ-R may be a useful instrument to examine the relationship between cognitive distortions and disability in a variety of illnesses, and to differentiate primary depression from overlapping somatic disorders.

Am Psychol 1997 Sep;52(9):973-983; Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome.; Jason LA, Richman JA, Friedberg F, Wagner L, Taylor R, Jordan KM; Department of Psychology, DePaul University, Chicago, IL 60614, USA.

Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. By the mid-1990s, findings from more representative epidemiological studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders. Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.

Optom Vis Sci 1997 Aug;74(8):660-663; An investigation of sympathetic hypersensitivity in chronic fatigue syndrome.; Sendrowski DP, Buker EA, Gee SS; Southern California College of Optometry, Fullerton, USA.

BACKGROUND: There are many theories, but the etiology of chronic fatigue syndrome (CFS) remains unknown. Diagnosticians have set guidelines to try to classify the condition, but its clinical definition is one of exclusion rather than defined by specific clinical testing. The primary goal of this investigation was to find a diagnostic key to define CFS. CFS patients and those diagnosed with the sympathetic hypersensitivity condition called fibromyalgia syndrome (FMS) exhibit identical brain single photon emission computerized tomography (SPECT) images. Therefore, this investigation was initiated to see if CFS patients also had denervation hypersensitivity of the sympathetic system. METHODS: A standardized supersensitivity test was performed using an ocular instillation of two drops of 1.0% phenylephrine. Sixty-two subjects (29 CFS patients and 33 normals) participated in the study. Measurements of pupil size were recorded by pupil gauge and flash photography. A pupillary dilation of greater than 2.5 mm would suggest a sympathetic denervation hypersensitivity. RESULTS: For all participants, a small, but statistically significant increase in pupil size was found (mean of 0.788 mm in normals and 0.931 mm in CFS patients). The change in pupil size in the CFS patients and controls showed substantial overlap and was not statistically significant (t = 0.83, p = 0.42, dF = 60). CONCLUSION: In conclusion, the results suggest that a denervation hypersensitivity of the pupil does not occur in CFS patients. The use of 1.0% topical phenylephrine had no diagnostic value in detecting CSF patients vs. normals.

Ned Tijdschr Geneeskd 1997 Aug 2;141(31):1520-1523; [Prevalence of chronic fatigue syndrome and primary fibromyalgia syndrome in The Netherlands]. Bazelmans E, Vercoulen JH, Galama JM, van Weel C, van der Meer JW, Bleijenberg G; Afd. Medische Psychologie, Academisch Ziekenhuis, Nijmegen.

OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) and of primary fibromyalgia syndrome (PFS) in the Netherlands. DESIGN: Questionnaire. SETTING: Department of Medical Psychology, University Hospital Nijmegen, the Netherlands. METHOD: A questionnaire was mailed to all the 6657 general practitioners in the Netherlands in order to inform them of the existence of CFS and to ask them if they had any CFS or PFS patients in their practices. RESULTS: Sixty percent (n = 4027) of the general practitioners returned the questionnaire. Of all the general practitioners, 27% said they had no CFS patients, 23% said they had 1 CFS patient, while 21% had 2 CFS patients, and 29% said they had 3 or more 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.

Ned Tijdschr Geneeskd 1997 Aug 2;141(31):1513-1516; [Chronic fatigue syndrome in young persons]. de Jong LW, Prins JB, Fiselier TJ, Weemaes CM, Meijer-van den Bergh EM, Bleijenberg G Afd. Medische Psychologie, Academisch Ziekenhuis, Nijmegen.

The prevalence of chronic fatigue syndrome (CFS) in teenagers is 10-20 per 100,000 inhabitants in the Netherlands. The natural course of the disorder is not favourable according to the literature. Proposed criteria for the diagnosis 'CFS' in adolescence are: absence of a physical explanation for the complaints, a disabling fatigue for at least six months and prolonged school absenteeism or severe motor and social 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.

Lakartidningen 1997 Jul 9;94(28-29):2555-2560; Enterovirus infections in new disguise.; Fohlman J, Friman G, Tuvemo T; Infektionskliniken, Akademiska sjukhuset, Uppsala.

Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of well known diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown. Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.

J Interferon Cytokine Res 1997 Jul;17(7):377-385; Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome.; Suhadolnik RJ, Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, Meirleir KD, Becker PD, Charubala R, Pfleiderer W; Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA, USA.

Previous studies from this laboratory have demonstrated a statistically significant dysregulation in several key components of the 2',5'-oligoadenylate (2-5A) synthetase/RNase L and PKR antiviral pathways in chronic fatigue syndrome (CFS) (Suhadolnik et al. Clin Infect Dis 18, S96-104, 1994; Suhadolnik et al. In Vivo 8, 599-604, 1994). Two methodologies have been developed to further examine the upregulated RNase L activity in CFS. First, photoaffinity labeling of extracts of peripheral blood mononuclear cells (PBMC) with the azido 2-5A photoaffinity probe, [32P]pApAp(8-azidoA), followed by immunoprecipitation with a polyclonal antibody against recombinant, human 80-kDa RNase L and analysis under denaturing conditions. A subset of individuals with CFS was identified with only one 2-5A binding protein at 37 kDa, whereas in extracts of PBMC from a second subset of CFS PBMC and from healthy controls, photolabeled/immunoreactive 2-5A binding proteins were detected at 80, 42, and 37 kDa. Second, analytic gel permeation HPLC was completed under native conditions. Extracts of healthy control PBMC revealed 2-5A binding and 2-5A-dependent RNase L enzyme activity at 80 and 42 kDa as determined by hydrolysis of poly(U)-3'-[32P]pCp. A subset of CFS PBMC contained 2-5A binding proteins with 2-5A-dependent RNase L enzyme activity at 80, 42, and 30 kDa. However, a second subset of CFS PBMC contained 2-5A binding and 2-5A-dependent RNase L enzyme activity only at 30 kDa. Evidence is provided indicating that the RNase L enzyme dysfunction in CFS is more complex than previously reported.

Cranio 1997 Jul;15(3):267-269; Ehlers-Danlos syndrome, fibromyalgia and temporomandibular disorder: report of an unusual combination. Miller VJ, Zeltser R, Yoeli Z, Bodner L; Department of Conservative Dentistry, Faculty of Health Sciences, School of Oral Health Science, South Africa.

An unusual case of temporomandibular disorder in the presence of both fibromyalgia and Ehlers-Danlos syndrome is presented. Some of the problems in treating these patients are discussed. It is suggested that early conservative treatment of the temporomandibular disorder with a stabilization splint and physical therapy is effective, and this approach should be attempted before any surgical intervention is chosen.

Am J Med 1997 Jul;103(1):38-43; Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.; Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, Tymms K, Wakefield D, Dwyer J, Lloyd A; Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.

PURPOSE: To determine whether the reported therapeutic benefit of intravenous immunoglobulin in patients with chronic fatigue syndrome (CFS) is dose dependent. PATIENTS AND METHODS: Ninety-nine adult patients, who fulfilled diagnostic criteria for CFS, participated in this double-blind, randomized, and placebo-controlled trial. Patients received intravenous infusions with either a placebo solution (1% albumin) or one of three doses of immunoglobulin (0.5, 1, or 2 g/kg) on a monthly basis for 3 months, followed by a treatment-free follow-up period of 3 months. Outcome was assessed by changes in a series of self-reported measures (quality-of-life visual analog scales, standardized diaries of daily activities, the profile of mood states questionnaire) and the Karnofsky performance scale. Cell-mediated immunity was evaluated by T-cell subset analysis and delayed-type hypersensitivity (DTH) skin testing. RESULTS: No dose of intravenous immunoglobulin was associated with a specific therapeutic benefit. Adverse reactions, typically constitutional symptoms, were reported by 70% to 80% of patients, with no relationship to immunoglobulin treatment. CONCLUSIONS: Intravenous immunoglobulin cannot be recommended as a therapy for the treatment of CFS. A better understanding of the pathophysiology of this disorder is needed before effective treatment can be developed.

Psychosomatics 1997 Jul;38(4):356-362; Cognitive behavior therapy for functional somatic complaints. The example of chronic fatigue syndrome.; Sharpe M; University of Edinburgh, Royal Edinburgh Hospital, United Kingdom.

Somatic complaints such as pain and fatigue that are unexplained by conventional disease are common in medical practice and are referred to as functional, somatoform, or somatization symptoms. Despite frequent chronicity, disability, and high associated medical costs, patients with these complaints are rarely offered either constructive explanations or effective treatment. In this perspective, a cognitive-behavioral approach to the problem is described, using chronic fatigue syndrome as an example. It is concluded that the utility of the cognitive-behavioral theory and the proven effectiveness cognitive behavior therapy provide the basis for a new evidence-based approach to psychosomatics.

Hosp Pract (Off Ed) 1997 Jun 15;32(6):147-150; Meeting the frustrations of chronic fatigue syndrome.; Plioplys AV, Plioplys S, Davis JS 4th; Department of Neurology, University of Illinois College of Medicine at Chicago, USA.

Patients face long-term disability, a variable prognosis, and too often, skeptical or misinformed doctors. Physicians lack laboratory markers or definitive treatment. Nevertheless, the diagnosis can be made with confidence by applying established diagnostic criteria - and selected laboratory studies to exclude other disorders - while symptomatic medication can provide support until recovery begins.

BMJ 1997 Jun 7;314(7095):1647-1652; Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome.; Fulcher KY, White PD; National Sports Medicine Institute, St Bartholomew's, London.

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome. DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination. SETTING: Chronic fatigue clinic in a general hospital department of psychiatry. SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance. INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards. MAIN OUTCOME MEASURE: The self rated clinical global impression change score, "very much better" or "much better" being considered as clinically important. RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment. CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.

J Psychosom Res 1997 Jun;42(6):615-624; Chronic fatigue syndrome: a qualitative investigation of patients' beliefs about the illness.; Clements A, Sharpe M, Simkin S, Borrill J, Hawton K; Department of Psychiatry, University of Oxford, Warneford Hospital, UK. alison.clements@psychiatry.ox.ac.uk

The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is physical in nature and minimize the role of psychological and social factors. There is also evidence that patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by 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.

J Psychosom Res 1997 Jun;42(6):597-605; The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome.; Morriss RK, Wearden AJ, Battersby L; University of Manchester, Department of Community Psychiatry, UK.

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.

J Nerv Ment Dis 1997 Jun;185(6):359-367; The quality of life of persons with chronic fatigue syndrome.; Anderson JS, Ferrans CE; University of Illinois at Chicago Medical Center, Department of Psychiatry 60612, USA.

This descriptive study used a between-methods triangulation design to analyze the multiple dimensions of quality of life in persons with chronic fatigue syndrome (CFS). This method, which refers to the combination of both quantitative and qualitative methods in the same study, allowed the authors to obtain 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.

Clin Infect Dis 1997 Jun;24(6):1048-1051; Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review.; Jacobson SK, Daly JS, Thorne GM, McIntosh K; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

The spectrum of disease caused by parvovirus B19 has been expanding in recent years because of improved and more sensitive methods of detection. There is evidence to suggest that chronic infection occurs in patients who are not detectably immunosuppressed. We report the case of a young woman with recurrent fever and a syndrome indistinguishable from chronic fatigue syndrome. After extensive investigation, we found persistent parvovirus B19 viremia, which was detectable by polymerase chain reaction (PCR) despite the presence of IgM and IgG antibodies to parvovirus B19. Testing of samples from this patient suggested that in some low viremic states parvovirus B19 DNA is detectable by nested PCR in plasma but not in serum. The patient's fever resolved with the administration of intravenous immunoglobulin.

Neurology 1997 Jun;48(6):1717-1719; Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome.; Plioplys AV; Chronic Fatigue Syndrome Center, Mercy Hospital, Chicago, IL, USA.

Chronic fatigue syndrome (CFS) patients suffer from disabling physical and mental fatigue. Circulating autoimmune antibodies may produce symptoms of muscular fatigue by reacting with acetylcholine receptors or calcium binding channels. They can also produce mental status changes by reacting with central nervous system (CNS) antigens. We thoroughly investigated the presence of circulating antimuscle and anti-CNS antibodies in 10 CFS patients and 10 controls. We were unable to detect any pathogenic antibodies.

Psychoneuroendocrinology 1997 May;22(4):261-267; Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.; Dinan TG, Majeed T, Lavelle E, Scott LV, Berti C, Behan P; Department of Psychological Medicine, St Bartholomew's Hospital, London, UK. T.G.Dinan@mds.qmw.ac.uk

We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods 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.

Gen Hosp Psychiatry 1997 May;19(3):185-199; Chronic fatigue syndrome. A practical guide to assessment and management.; Sharpe M, Chalder T, Palmer I, Wessely S; University of Edinburgh, UK.

Chronic fatigue and chronic fatigue syndrome (CFS) have become increasingly recognized as a common clinical problem, yet one that physicians often find difficult to manage. In this review we suggest a practical, pragmatic, evidence-based approach to the assessment and initial management of the patient whose presentation suggests this diagnosis. The basic principles are simple and for each aspect of management we point out both potential pitfalls and strategies to overcome them. The first, and most important task is to develop mutual trust and collaboration. The second is to complete an adequate assessment, the aim of which is either to make a diagnosis of CFS or to identify an alternative cause for the patient's symptoms. The history is most important and should include a detailed account of the symptoms, the associated disability, the choice of coping strategies, and importantly, the patient's own understanding of his/her illness. The assessment of possible comorbid psychiatric disorders such as depression or anxiety is mandatory. When the physician is satisfied that no alternative physical or psychiatric disorder can be found to explain symptoms, we suggest that a firm and positive diagnosis of CFS be made. The treatment of CFS requires that the patient is given a positive explanation of the cause of his symptoms, emphasizing the distinction among factors that may have predisposed them to develop the illness (lifestyle, work stress, personality), triggered the illness (viral infection, life events) and perpetuated the illness (cerebral dysfunction, sleep disorder, depression, inconsistent activity, and misunderstanding of the illness and fear of making it worse). Interventions are then aimed to overcoming these illness-perpetuating factors. The role of antidepressants remains uncertain but may be tried on a pragmatic basis. Other medications should be avoided. The only treatment strategies of proven efficacy are cognitive behavioral ones. The most important starting point is to promote a consistent pattern of activity, rest, and sleep, followed by a gradual return to normal activity; ongoing review of any 'catastrophic' misinterpretation of symptoms and the problem solving of current life difficulties. We regard chronic fatigue syndrome as important not only because it represents potentially treatable disability and suffering but also because it provides an example for the positive management of medically unexplained illness in general.

J R Soc Med 1997 May;90(5):250-254; Chronic fatigue syndrome: sufferers' evaluation of medical support.; Ax S, Gregg VH, Jones D; Birkback College, University of London, England.

In response to reports of negative cooperation between sufferers of chronic fatigue syndrome (CFS) and their doctors, semi-structured interviews were conducted with sufferers from two different patient samples. 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.

Acta Psychiatr Scand 1997 May;95(5):405-413; Generalized anxiety disorder in chronic fatigue syndrome.; Fischler B, Cluydts R, De Gucht Y, Kaufman L, De Meirleir K; Department of Psychiatry, Academic Hospital, Brussels, Balgium.

A structured psychiatric interview, forming part of a global psychopathological approach, revealed higher prevalence rates of current and lifetime psychiatric disorders and a higher degree of psychiatric comorbidity in patients with chronic fatigue syndrome (CFS) than in a medical control group. In contrast to previous studies, a very high prevalence of generalized anxiety disorder (GAD) was found in CFS, characterized by an early onset and a high rate of psychiatric comorbidity. It is postulated that GAD represents a susceptibility factor for the development of CFS. A significantly higher prevalence was also observed for the somatization disorder (SD) in the CFS group. Apart from a higher female-to-male ratio in fibromyalgia, no marked differences were observed in sociodemographic or illness-related features, or in psychiatric morbidity, between CFS patients with and without fibromyalgia. CFS patients with SD have a longer illness duration and a higher rate of psychiatric comorbidity. These findings are consistent with the suggestion of Hickie et al. (1) that chronic fatigued subjects with SD should be distinguished from subjects with CFS.

J Clin Immunol 1997 May;17(3):253-261; Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome.; Cannon JG, Angel JB, Abad LW, Vannier E, Mileno MD, Fagioli L, Wolff SM, Komaroff AL; Department of Medicine, Tufts University-New England Medical Center, Boston, Massachusetts 02111, USA.

Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which include fatigue, myalgia, and low-grade fever, are similar to those experienced by patients infused with cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular secretion of interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), and soluble 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 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.

J Neuroimmunol 1997 May;75(1-2):183-195; Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.; Vedhara K, Llewelyn MB, Fox JD, Jones M, Jones R, Clements GB, Wang EC, Smith AP, Borysiewicz LK; Department of Medicine, University of Wales College of Medicine, Cardiff, UK. k.vedhara@bristol.ac.uk

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

Med Klin 1997 Apr 15;92(4):221-227; Definition of "chronic fatigue syndrome".; Heyll U, Wachauf P, Senger V, Diewitz M; Gesellschaftsarztliche Abteilung der Deutschen Krankenversicherung, Koln.

The definition of "Chronic Fatigue Syndrome" (CFS) in 1988 was an attempt to establish a uniform basis for the previously heterogeneous approaches to research of this severe and inexplicable state of fatigue. At the same time, researchers wished to narrow down a pathogenetically founded disease entity a priori by specifying precise disease criteria. The empirical data gathered in accordance with the CFS definition, however, have failed to confirm the assumption that the disease entity is pathogenetically uniform. Furthermore, the originally selected criteria have proven to be impracticable ore theoretically questionable. In the period that followed, modifications that permitted a more comprehensive and yet more differentiated classification of fatigue states of unclear etiology were proposed. The new research approach avoids postulation of causal entities and puts CFS back in a category with other descriptive states of fatigue.

Arch Intern Med 1997 Apr 14;157(7):750-754; Epidemic neuromyasthenia and chronic fatigue syndrome in west Otago, New Zealand. A 10-year follow-up.; Levine PH, Snow PG, Ranum BA, Paul C, Holmes MJ; Department of Medicine, George Washington University Medical Center, Washington, DC, USA.

BACKGROUND: In 1984, an outbreak of an illness characterized by prolonged unexplained fatigue was reported in West Otago, New Zealand. This outbreak resembled other reported outbreaks of epidemic neuromyasthenia in that affected individuals presented with a spectrum of complaints ranging from transient diarrhea and upper respiratory disorders to chronic fatigue syndrome (CFS). OBJECTIVE: To obtain a perspective on the natural history of CFS not possible in clinic-based studies. METHODS: Twenty-three of the 28 patients in the original report were contacted and asked to complete written questionnaires. Interviews were obtained in person or via telephone. RESULTS: Ten (48%) of the 21 patients with satisfactory interviews appeared to meet the current Centers for Disease Control and Prevention (CDC) case definition of CFS, and 11 were classified as having prolonged or idiopathic fatigue. A return to premorbid activity was seen in most (n = 16) patients, although some reported the need to modify their lifestyle to prevent relapses. A female predominance was noted in those meeting the CDC case definition for CFS, whereas males predominated in patients diagnosed as having prolonged or idiopathic fatigue. CONCLUSIONS: The high proportion of patients recovering from CFS in the West Otago cluster suggests that epidemic-associated CFS has a better prognosis than sporadic cases. Female sex was confirmed as an important risk factor for CFS.

Am J Med 1997 Apr;102(4):357-364; Does the chronic fatigue syndrome involve the autonomic nervous system? Freeman R, Komaroff AL; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and predisposition to neurally mediated syncope reported in this patient group. PATIENTS AND METHODS: Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and premorbid and coexisting psychiatric disorders. The relationship between autonomic test results, cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic neuropathy was explored. RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01) and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P < 0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function (systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P < 0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twenty-five percent of CFS subjects had a positive tilt table test. The physical activity index was a significant predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy. CONCLUSION: Patients with CFS show alterations in measures of sympathetic and parasympathetic nervous system function. These results, which provide the physiological basis for the orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.

J Anal Psychol 1997 Apr;42(2):237-251; A view of the violence contained in chronic fatigue syndrome.; Bennett A

In this paper I ask whether there might be any one particular psychopathology likely to be linked specifically with the physical illness known as chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), and whether CFS/ME aids and abets and "fits' an original mental state. I think the 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.

J Anal Psychol 1997 Apr;42(2):217-236; Coniunctio--in bodily and psychic modes: dissociation, devitalization and integration in a case of chronic fatigue syndrome.; Holland P; Psychotherapy Department, Royal Edinburgh Hospital.

Three years of analytical psychotherapy with a professional woman in mid-life, suffering from chronic fatigue syndrome (CFS), is described. Gradual recovery merged into mid-life changes; marriage, along with a new balance of maternal and paternal imagos, enabled her to trust enough to become pregnant-coniunctio in the most primal bodily and psychic modes. Her life-long, schizoid type pattern, "the pendulum of closeness and isolation', with its extreme of psycho-physical collapse and devitalization, was replayed in therapy. The analyst's symbolic attitude is emphasized, containing the patient's initial affective explosion and validating the physicality of her condition. Mirroring and steady rhythmic attunement became a new, pre-verbal, source of trust-vitalization; differentiation and separation replaced defensive splitting and dissociation. Then the overwhelmingly powerful bodily/maternal could be counterbalanced by the masculine, and a transitional space emerged for symbolic work. Both the regressive and the dynamic aspects of CFS are located in the earliest undifferentiated, archetypal, bodily/psychic modes, when the frustration of primary needs evokes the defences of the self. It is argued that our psychodynamic understanding can contribute to the stalemate in seeing chronic fatigue syndrome as either an organic illness or depression, and that a new linking of the somatic and psychic calls for a new professional collaboration.

J Anal Psychol 1997 Apr;42(2):201-216; A body with chronic fatigue syndrome as a battleground for the fight to separate from the mother.; Simpson M

I describe the therapy of a 20-year-old women who believed that her difficulties in concentrating and remembering were caused by her "ME' (Myalgic encephalomyelitis, Chronic fatigue syndrome, or CFS). She had been fathered by a man who never left his own wife. Work with her dreams revealed a within-body drama in which she was locked in an unspeakable fight to the death with her mother. Her symptoms improved after parallels between a dream and an accident showed her own self-destructive hand in her story. Another dream, reflecting her first 'incestuous' affair, showed her search for her original father-self as someone separate from mother, and a later affair provided a between-body drama, helping her to own the arrogant and abject traits she had before seen only as her mother's. I show how we worked in the area of Winnicott's first 'primitive agony' as experienced by a somatizing patient, stuck in a too-close destructive relationship with her mother-body. I discuss how analytical work can be done with the primitive affects and conflicts against which the ME symptoms may be defending.

J Anal Psychol 1997 Apr;42(2):191-199; Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century disease: analytic challenges.; Simpson M, Bennett A, Holland P

The challenges of chronic fatigue syndrome (often called myalgic encephalomyelitis, especially in the UK) (CFS/ME) to analytical and medical approaches are connected with our inability to understand its distressing somatic symptoms in terms of a single identifiable and understandable disease entity. The evidence for the roles of viral aetiologies remains inconclusive, as does our understanding of the involvement of the immune system. The history and social context of CFS/ME, and its relation to neurasthenia and psychasthenia are sketched. A symbolic attitude to the condition may need to be rooted in an awareness of psychoid levels of operation, and the expression and spread of CFS/ME may sometimes be aided by the ravages of projective identification. Psychic denial, sometimes violent, in sufferers (especially children and adolescents) and their families may be important in the aetiology of CFS/ME. We draw out common threads from psychodynamic work with five cases, four showing some symptomatic improvement, analytic discussions of three cases being presented elsewhere in this issue of JAP.

J Psychosom Res 1997 Apr;42(4):369-378; Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology.; Fischler B, Dendale P, Michiels V, Cluydts R, Kaufman L, De Meirleir K; Department of Psychiatry, Academic Hospital, Free University of Brussels, Belgium.

Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart rate, THR) during incremental exercise. The association with functional status impairment, somatization, and psychopathology was examined. A statistically significant association was demonstrated between this physical fatigability variable and impairment, and a trend was found for an association with somatization. No association was demonstrated with psychopathology. These results are in accordance with the cognitive-behavioral model of CFS, suggesting a major contribution of avoidance behavior to functional status impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior. Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup. Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.

Dent Clin North Am 1997 Apr;41(2):279-296; Psychoneuroimmunology and its relationship to the differential diagnosis of temporomandibular disorders.; Auvenshine RC

Psychoneuroimmunology (PNI) is a field of medicine which joins immunology and neurobiology. It focuses on the relationship of stress upon the hypothalamic-adrenal-pituitary (HPA) axis. Depletion of hormones and neurotransmitters within the HPA-axis, as a result of stress, can lead to a multitude of diseases and disorders. Therefore, it is necessary for the dentist to be familiar with PNI and the HPA-axis in order to make an accurate diagnosis of TMD.

Eur J Clin Invest 1997 Apr;27(4):257-267; Chronic fatigue syndrome--aetiological aspects.; Dickinson CJ; Wolfson Institute of Preventive Medicine, St. Bartholomew's & Royal London School of Medicine & Dentistry, London, UK.

The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition there are no consistently abnormal physical signs or abnormalities on laboratory investigation. Many physicians remain convinced that the symptoms are psychological rather than physical in origin. This view is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms 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.

Psychol Rep 1997 Apr;80(2):643-658; Patterns of utilization of medical care and perceptions of the relationship between doctor and patient with chronic illness including chronic fatigue syndrome.; Twemlow SW, Bradshaw SL Jr, Coyne L, Lerma BH; University of Kansas School of Medicine, Wichita, USA.

To what extent do personal constructs affect the relationship between doctor and patient when the ill patient does not readily recover with treatment? Questionnaires were returned anonymously by 609 patients with a self-reported diagnosis of chronic fatigue syndrome, who were considered chronically ill. Findings were compared with those of an earlier study of a population of 397 general medical patients. The chronically ill patients lost an average of 65 days of work per year due to illness compared to general medical patients who missed six or fewer days per year because they were ill. The chronically ill patients also reported a 66% higher frequency of iatrogenic illness, spent more money on health care, took more medication, saw more specialists, and were more litigious than the general medical population. Research suggested several patterns of relationships between doctors and patients, and attitudes to health and illness, which may alert doctors to patients' perceptions, beliefs, encoded constructs, and patterns of relating that affect responses to treatment. More attention by doctors to patients who are experiencing the stress of chronic illness is indicated.

Environ Health Perspect 1997 Mar;105 Suppl 2:417-436; Profile of patients with chemical injury and sensitivity.; Ziem G, McTamney J; Occupational and Environmental Medicine, Baltimore, Maryland, USA.

Patients reporting sensitivity to multiple chemicals at levels usually tolerated by the healthy population were administered standardized questionnaires to evaluate their symptoms and the exposures that aggravated these symptoms. Many patients were referred for medical tests. It is thought that patients with chemical sensitivity have organ abnormalities involving the liver, nervous system (brain, including limbic, peripheral, autonomic), immune system, and porphyrin metabolism, probably reflecting chemical injury to these systems. Laboratory results are not consistent with a psychologic origin of chemical sensitivity. Substantial overlap between chemical sensitivity, fibromyalgia, and chronic fatigue syndrome exists: the latter two conditions often involve chemical sensitivity and may even be the same disorder. Other disorders commonly seen in chemical sensitivity patients include headache (often migraine), chronic fatigue, musculoskeletal aching, chronic respiratory inflammation (rhinitis, sinusitis, laryngitis, asthma), attention deficit, and hyperactivity (affected younger children). Less common disorders include tremor, seizures, and mitral valve prolapse. Patients with these overlapping disorders should be evaluated for chemical sensitivity and excluded from control groups in future research. Agents whose exposures are associated with symptoms and suspected of causing onset of chemical sensitivity with chronic illness include gasoline, kerosene, natural gas, pesticides (especially chlordane and chlorpyrifos), solvents, new carpet and other renovation materials, adhesives/glues, fiberglass, carbonless copy paper, fabric softener, formaldehyde and glutaraldehyde, carpet shampoos (lauryl sulfate) and other cleaning agents, isocyanates, combustion products (poorly vented gas heaters, overheated batteries), and medications (dinitrochlorobenzene for warts, intranasally packed neosynephrine, prolonged antibiotics, and general anesthesia with petrochemicals). Multiple mechanisms of chemical injury that magnify response to exposures in chemically sensitive patients can include neurogenic inflammation (respiratory, gastrointestinal, genitourinary), kindling and time-dependent sensitization (neurologic), impaired porphyrin metabolism (multiple organs), and immune activation.

Curr Opin Rheumatol 1997 Mar;9(2):135-143; Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.; Goldenberg DL

The diagnosis of fibromyalgia continues to generate heated debate. The presence of multiple lifetime psychiatric diagnoses was not intrinsically related to fibromyalgia but rather to the decision of patients to seek specialty medical care. Better outcome measures in fibromyalgia were tested. Neurally mediated hypotension may be associated with chronic fatigue syndrome (CFS). Treatment of patients with fibromyalgia and CFS continues to be of limited success, although the role of multidisciplinary group intervention appears promising. Two position papers focused on the adverse aspects of the medicolegal issues in fibromyalgia and CFS.

QJM 1997 Mar;90(3):223-233; The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. Joyce J, Hotopf M, Wessely S; Institute of Psychiatry, London, UK.

The prognosis of chronic fatigue syndrome and chronic fatigue has been studied in numerous small case series. We performed a systematic review of all studies to determine the proportion of individuals with the conditions who recovered at follow-up, the risk of developing alternative physical diagnoses, and the risk factors for poor prognosis. A literature search of all published studies which included a follow-up of patients with chronic fatigue syndrome or chronic fatigue were performed. Of 26 studies identified, four studied fatigue in children, and found that 54-94% of children recovered over the periods of follow-up. Another five studies operationally defined chronic fatigue syndrome in adults and found that <10% of subjects return to pre-morbid levels of functioning, and the majority remain significantly impaired. The remaining studies used less stringent criteria to define their cohorts. Among patients in primary care with fatigue lasting ><6 months, at least 40% of patients improved. As the definition becomes more stringent the prognosis appears to worsen. Consistently reported risk factors for poor prognosis are older age, more chronic illness, having a comorbid psychiatric disorder and holding a belief that the illness is due to physical causes.

Psychol Med 1997 Mar;27(2):343-353; A population-based incidence study of chronic fatigue.; Lawrie SM, Manders DN, Geddes JR, Pelosi AJ; Edinburgh University Department of Psychiatry, Royal Edinburgh Hospital.

BACKGROUND: Most research on syndromes of chronic fatigue has been conducted in clinical settings and is therefore subject to selection biases. We report a population-based incidence study of chronic fatigue (CF) and chronic fatigue syndrome (CFS). METHODS: Questionnaires assessing fatigue and emotional morbidity were sent to 695 adult men and women who had replied to a postal questionnaire survey 1 year earlier. Possible CFS cases, subjects with probable psychiatric disorder and normal controls were interviewed. RESULTS: Baseline fatigue score, the level of emotional morbidity and a physical attribution for fatigue were risk factors for developing CF. However, after adjusting for confounding, premorbid fatigue score was the only significant predictor. A minority of CF subjects, all female, had consulted their general practitioner; higher levels of both fatigue and emotional morbidity were associated with consultation. Possible CFS cases reported similar rates of current and past psychiatric disorder to psychiatric controls, but after controlling for fatigue or a diagnosis of neurasthenia the current rates were more similar to those of normal controls. Two new cases of CFS were confirmed. CONCLUSIONS: Both fatigue and emotional morbidity are integral components of chronic fatigue syndromes. The demographic and psychiatric associations of CFS in clinical studies are at least partly determined by selection biases. Given that triggering and perpetuating factors may differ in CFS, studies that examine the similarities and differences between chronic fatigue syndromes and psychiatric disorder should consider both the stage of the illness and the research setting.

J Clin Immunol 1997 Mar;17(2):160-166; Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.; Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH, Peterson PK, Komaroff AL; Chronic Fatigue Syndrome Cooperative Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta 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.

Clin Orthop 1997 Mar;336:52-60; Somatization and chronic pain in historic perspective.; Shorter E; History of Medicine Program, Faculty of Medicine, University of Toronto, Ontario, Canada.

Practitioners today are confronted with an avalanche of difficult to treat patients with chronic pain for 2 reasons: (1) The culture increasingly encourages patients to conceive vague and nonspecific symptoms as evidence of real disease and to seek specialist help for them; and (2) the rising ascendancy of the media and the breakdown of the family encourage patients to acquire the fixed belief that they have a given illness, often a trendy nondisease such as repetition strain injury or chronic fatigue syndrome. In historic terms, many of these complaints, especially sensory ones featuring chronic pain and chronic fatigue, are relatively new. Patients tend to adopt them on the basis of what the culture considers to be legitimate illness, whereby different patterns exist for men and women.

Am J Psychiatry 1997 Mar;154(3):408-414; Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial.; Deale A, Chalder T, Marks I, Wessely S; Academic Department of Psychological Medicine, King's College Hospital, London, United Kingdom.

OBJECTIVE: Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a randomized controlled trial. METHODS: Sixty patients with chronic fatigue syndrome were randomly assigned to 13 sessions of either cognitive behavior therapy (graded activity and cognitive restructuring) or 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.

Biol Psychiatry 1997 Mar 1;41(5):567-573; Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome.; Allain TJ, Bearn JA, Coskeran P, Jones J, Checkley A, Butler J, Wessely S, Miell JP; Department of Medicine, Kings College School of Medicine and Dentistry, London, United Kingdom.

Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin. Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia. 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.

Ann Med 1997 Feb;29(1):9-21; The fibromyalgia syndrome.; Wallace DJ; Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, USA.

The term fibromyalgia describes a complex syndrome characterized by pain amplification, musculoskeletal discomfort, and systemic symptoms. Although its existence has been controversial, nearly all rheumatologists now accept fibromyalgia as a distinct diagnostic entity. In fact, in the United States it is the third or fourth most common reason for rheumatology referral. Exciting new insights into the aetiology, pathogenesis, diagnosis and treatment of fibromyalgia will be reviewed.

J Neurol Neurosurg Psychiatry 1997 Feb;62(2):151-155; Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease.; DeLuca J, Johnson SK, Ellis SP, Natelson BH; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, USA.

OBJECTIVE: To examine the effect of the presence or absence of psychiatric disease on cognitive functioning in chronic fatigue syndrome. METHODS: Thirty six patients with chronic fatigue syndrome and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue 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.

Arthritis Rheum 1997 Feb;40(2):295-305; High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome.; von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM; Institut fur Umwelthygiene, Heinrich Heine Universitat Dusseldorf, Germany.

OBJECTIVE: To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies. METHODS: Initial immunofluorescence histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate. RESULTS: Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty-eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%). CONCLUSION: The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.

J Rheumatol 1997 Feb;24(2):372-376; Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome.; Buchwald D, Wener MH, Pearlman T, Kith P; Department of Medicine, University of Washington, Seattle, USA.

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition. METHODS: Assays for soluble 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.

J Gen Virol 1997 Feb;78( Pt 2):307-312; Evidence for enteroviral persistence in humans.; Galbraith DN, Nairn C, Clements GB; Regional Virus Laboratory, Ruchill Hospital, Glasgow, UK.

We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at least 5 months apart. The nucleotide sequence of the 5' non-translated region (bases 174-423) was determined for each amplicon. Four individuals had virtually identical nucleotide sequences ( 97%) in both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses. In the remaining three individuals, the lack of unique shared features suggested that re-infection had occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is related to the Coxsackie B-like viruses.

J Psychiatr Res 1997 Jan;31(1):149-156; Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome.; Gupta S, Aggarwal S, See D, Starr A; Department of Medicine, University of California, Irvine 92717, USA.

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS), respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also measured at the mRNA level by polymerase chain reaction. The levels of spontaneously (unstimulated) produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously studied matched controls. The abnormality of IL-6 was also observed at mRNA level. In contrast, spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may play a role in the pathogenesis and in some of the clinical manifestations of CFS.

J Psychiatr Res 1997 Jan;31(1):133-147; Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents.; Rowe KS; Department of Paediatrics, University of Melbourne Royal Children's Hospital, Victoria, Australia.

A double blind randomized controlled trial was conducted in 71 adolescents aged 11-18 years. Inclusion in the trial required fulfilment of the diagnostic criteria, (Fukuda et al., 1994). Three infusions of 1 gm/kg (max 1 litre of 6 gm/100 ml in 10% w/v maltose solution) were given one month apart. The dummy solution was a 10% w/v maltose solution with 1% albumin of equivalent volume for weight. Efficacy was assessed by difference in a mean functional score including school attendance, school work, social activity and physical activity, between baseline, three months and six months after the final infusion. There was a significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic Fatigue Syndrome of average duration 18 months. There was also a significant improvement for both groups from the beginning of the trial to the six month post infusion follow-up. Adverse effects were common with both solutions but not predictive of response. Neither solution could be identified by recipients.

J Psychiatr Res 1997 Jan;31(1):125-131; The relationship between fibromyalgia and interstitial cystitis.; Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J; Division of Rheumatology, Immunology and Allergy, Georgetown University Medical Center, Washington, D.C., USA.

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue 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.

J Psychiatr Res 1997 Jan;31(1):115-122; Electron microscopic immunocytological profiles in chronic fatigue syndrome. Holmes MJ, Diack DS, Easingwood RA, Cross JP, Carlisle B; Department of Microbiology, University of Otago, Dunedin, New Zealand. mike.holmes@stonebow.otago.ac.nz

Structures consistent in size, shape and character with various stages of a Lentivirus replicative cycle were observed by electron microscopy in 12-day peripheral-blood lymphocyte cultures from 10 of 17 Chronic Fatigue Syndrome patients and not in controls. Attempts to identify a lymphoid phenotype containing these structures by immunogold labelling failed and the results of reverse-transcriptase assay of culture supernatants were equivocal. The study was blind and case-controlled, patients being paired with age, sex and ethnically matched healthy volunteers. Prescreening of subjects included the common metabolic and immunological disorders, functional conditions and a virus-screen against hepatitis B and C, Epstein-Barr Virus, Cytomegalovirus and Human Immunodeficiency Virus.

J Psychiatr Res 1997 Jan;31(1):99-113; Gender differences in host defense mechanisms.; Cannon JG, St Pierre BA; Intercollege Physiology Program, Pennsylvania State University, University Park 16802-6900, USA.

Extensive studies in both humans and animals have shown that females express enhanced levels of immunoreactivity compared to males. Whereas this provides females with increased resistance to many types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on 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.

J Psychiatr Res 1997 Jan;31(1):91-96; Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome.; Bennett AL, Mayes DM, Fagioli LR, Guerriero R, Komaroff AL; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy 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.

J Psychiatr Res 1997 Jan;31(1):83-90; Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures.; DeLuca J, Johnson SK, Ellis SP, Natelson BH; UMDNJ-New Jersey Medical School, Newark, USA.

To examine the influence of mode of illness onset on psychiatric status and neuropsychological performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms. These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS 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.

J Psychiatr Res 1997 Jan;31(1):69-82; Neuroendocrine correlates of chronic fatigue syndrome: a brief review.; Demitrack MA; Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.

Chronic fatigue syndrome remains one of the more perplexing syndromes in contemporary clinical medicine. One approach to understanding this condition has been to acknowledge its similarities to other disorders of clearer pathophysiology. In this review, a rationale for the study of neuroendocrine correlates of 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.

J Psychiatr Res 1997 Jan;31(1):59-65; Precipitating factors for the chronic fatigue syndrome.; Salit IE; Division of Infectious Diseases, Toronto Hospital, Ontario, Canada. irving.salit@utoronto.ca

The etiology of the Chronic Fatigue Syndrome (CFS) is unknown but it is usually considered to be postinfectious or postviral. Many infecting agents have been suspected as causative but none has been proven. We investigated precipitating factors in 134 CFS patients through the use of a questionnaire, interview, clinical examination and serology for infecting agents; 35 healthy controls completed a similar questionnaire. CFS started with an apparently infectious illness in 96 (72%) but a definite infection was only found in seven of these 96 (7%). Thirty-eight (28%) had no apparent infectious onset: 15/38 (40%) had noninfectious precipitants (trauma, allergy, surgery). There was no apparent precipitating event in 23/38 (61%). Immunization was not a significant precipitant. Stressful events were very common in the year preceding the onset of CFS (114/134, 85%) but these occurred in only 2/35 (6%) of the controls (p < .0001). The onset of CFS may be associated with preceding stressful events and multiple other precipitants. An infectious illness is not uniformly present at the onset and no single infectious agent has been found; CFS is most likely multifactorial in origin.

J Psychiatr Res 1997 Jan;31(1):51-57; The natural history of concurrent sick building syndrome and chronic fatigue syndrome.; Chester AC, Levine PH; Georgetown University Medical Center, Washington DC, USA.

An outbreak of chronic fatigue syndrome linked with sick building syndrome was recently described as a new association. Whether chronic fatigue syndrome acquired in this setting tends to remit or, as sporadic cases often do, persist, is unknown. To clarify the natural history of chronic fatigue syndrome in association 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.

J Psychiatr Res 1997 Jan;31(1):45-50; Chronic fatigue syndrome criteria in patients with other forms of unexplained chronic fatigue.; Chester AC; Georgetown University Medical Center, Washington D.C., USA.

To determine the prevalence of chronic fatigue syndrome (CFS) criteria in other forms of unexplained chronic fatigue, 297 consecutive outpatients under the age of 40 from a general medicine practice were studied. After excluding the three with chronic fatigue syndrome, the remaining 294 individuals were 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.

J Psychiatr Res 1997 Jan;31(1):19-29; An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome.; Fukuda K, Dobbins JG, Wilson LJ, Dunn RA, Wilcox K, Smallwood D; Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

We surveyed households in four rural Michigan communities to confirm a reported cluster of cases resembling chronic fatigue syndrome (CFS) and to study the epidemiology of fatigue in a rural area. Data were collected from 1698 households. We did not confirm the reported cluster. The prevalence of households containing at least one fatigued person was similar between communities thought to harbor the cluster and communities selected for comparison. Symptoms and features of generic forms of fatigue were very similar to those often attributed to CFS.

J Psychiatr Res 1997 Jan;31(1):7-18; Epidemiologic advances in chronic fatigue syndrome.; Levine PH; Department of Medicine, George Washington University Medical Center, Washington, D.C. 20037, USA.

Epidemiologic studies of chronic fatigue syndrome (CFS) have been hampered by the absence of a specific diagnostic test, but with increasing interest in this disorder there has been a greater understanding of the risk factors, illness patterns, and other aspects of this multisystem disorder. Working case definitions have been developed for research purposes but they have continued to change over time and have not always been utilized precisely by various investigators. This has been a major factor in the widely varying estimates of prevalence rates, but two different studies using the same working definition and including a medical work-up have estimated the prevalence to be approximately 200/100,000. Clusters of CFS cases, which appear to be related to earlier reports of "epidemic neuromyasthenia", have attracted considerable attention and appear to be well documented, although investigated with varying methodology and often with dissimilar case definitions. Risk factors for cases occurring in clusters and sporadically appear to be similar, the most consistent ones being female gender and the co-existence of some form of stress, either physical or psychological. The prognosis of CFS is difficult to predict, although cases occurring as part of clusters appear to have a better prognosis as a group than sporadic cases, and those with an acute onset have a better prognosis than those with gradual onset. It is highly unlikely that there is a single agent, infectious or noninfectious, that is responsible for more than a small proportion of CFS cases and, at the present time, the risk factors for developing CFS appear to lie more prominently in the host rather than the environment.

Pathobiology 1997;65(1):57-60; Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report.; Martin WJ; Center for Complex Infectious Diseases, Rosemead, Calif. 91770, USA. wjmartin@bcf.usc.edu

A cytopathic stealth virus was cultured from the cerebrospinal fluid of a nurse with chronic fatigue syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the patient's culture yielded positive results with primer sets based on sequences of a previously isolated African green monkey simian-cytomegalovirus-derived stealth virus. The same primer sets did not yield PCR products when tested directly on DNA extracted from the cultures. The findings lend support to the possibility of replicative RNA forms of certain stealth viruses and have important implications concerning the choice of therapy in this type of patient.

Int Clin Psychopharmacol 1997 Jan;12(1):47-52; An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome.; White PD, Cleary KJ; Department of Psychological Medicine, St Bartholomew's and the Royal London Medical School, UK.