Pain 1998 Aug;77(2):151-61 Menstrual cycle modulation of tender points. Hapidou EG, Rollman GB Chronic Pain Management Program, Chedoke Rehabilitation Services, Hamilton Health Sciences Corporation, Ontario, Canada. hapidou@fhs.csu.mcmaster.ca Changes in pain sensitivity throughout the menstrual cycle were assessed in 36 normally menstruating women and 30 users of oral contraceptives. Pain sensitivity was measured with palpation of rheumatological tender points and with pressure dolorimetry. The number of tender points identified by palpation was greater in the follicular (postmenstrual) phase of the cycle as compared to the luteal (intermenstrual) phase in normally cycling women but not in users of oral contraceptives. These findings are related to previously described physiological and psychological features of the menstrual cycle, with particular emphasis on the role of hormonal events in modulating pain perception, particularly in musculoskeletal disorders such as fibromyalgia. PMID: 9766833, UI: 98438223

Clin J Pain 1998 Sep;14(3):232-8 Comparison of integrated group therapy and group relaxation training for fibromyalgia. Keel PJ, Bodoky C, Gerhard U, Muller W University Psychiatric Outpatient Clinic, Basel, Switzerland. OBJECTIVE: The efficacy of an integrated, psychological treatment program was tested in a controlled study involving 27 patients with chronic musculoskeletal pain (fibromyalgia). DESIGN: The experimental treatment program consisted of instruction in various self-help techniques (e.g., cognitive behavioral strategies, relaxation, physical exercises) as well as information on chronic pain. Control groups were instructed only in autogenic training. Measures of pain, daily activities, general symptoms, and psychological functioning were assessed before and after treatment, as well as at 4 months after termination of therapy (follow-up). RESULTS: At the end of treatment, 7 patients from the experimental group and 2 from the control group showed significant clinical improvement in 3 of 6 parameters (NS). At follow-up, the improvement was still present in 5 experimental cases but in none of the controls (p = 0.024). Successful patients had been sick for a shorter period of time and were less impaired by their condition. CONCLUSIONS: Psychological interventions in combination with physiotherapy can be effective in treating fibromyalgia patients, especially if applied early. PMID: 9758073, UI: 98429040

JAMA 1998 Sep 23-30;280(12):1061-6 Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. McKenzie R, O'Fallon A, Dale J, Demitrack M, Sharma G, Deloria M, Garcia-Borreguero D, Blackwelder W, Straus SE Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA. CONTEXT: Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia. OBJECTIVE: To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS. DESIGN: A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996. SETTING: A single-center study in a tertiary care research institution. PATIENTS: A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications. INTERVENTION: Oral hydrocortisone, 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks. MAIN OUTCOME MEASURES: A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist. RESULTS: The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P =.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001). CONCLUSIONS: Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS. Publication Types: Clinical trial Randomized controlled trial PMID: 9757853, UI: 98428820

CMAJ 1998 Sep 8;159(5):533-4 Chronic fatigue syndrome get court's nod of approval as legitimate disorder. Capen K Lawyer Karen Capen looks at the implications of a recent Alberta court case involving chronic fatigue syndrome. She thinks Canada's physicians should pay close attention to this precedent-setting case. PMID: 9757183, UI: 98429734

Arthritis Rheum 1998 Sep;41(9):1689-94 Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue. Sprott H, Bradley LA, Oh SJ, Wintersberger W, Alarcon GS, Mussell HG, Tseng A, Gay RE, Gay S Friedrich Schiller University of Jena, Germany. OBJECTIVE: Because former investigations have reported abnormal changes in the expression of serotonin (5-hydroxytryptamine [5-HT]) and substance P (SP) in serum and cerebrospinal fluid, this study sought to determine whether 5-HT and pain-modulating neuropeptides (SP, galanin [GA], pituitary adenylyl cyclase-activating polypeptide, and secretoneurin) were expressed abnormally in the muscle tissue of patients with fibromyalgia (FM). METHODS: Snap-frozen muscle tissue specimens (deltoid muscles) from 10 patients with FM (mean disease duration 15 years) and from 10 healthy control subjects were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA preparations from muscle cells, and by immunohistochemistry methods (alkaline phosphatase-anti-alkaline phosphatase and immunogold-silver) using specific primers as well as antibodies. When specific messenger RNA (mRNA) was detected by RT-PCR, in situ RT-PCR was performed for mRNA localization. RESULTS: Specific mRNA for the examined substances was absent in 9 of 10 FM patients and in 10 of 10 controls. No differences between the FM patients and controls could be detected in the muscle tissue by immunohistochemistry. In 1 FM patient, mRNA for the GA receptor could be shown. CONCLUSION: This study showed that 5-HT and neuropeptides are not produced in the muscle of patients with FM, and therefore do not appear to be involved in the peripheral induction of pain in this chronic, painful disorder. PMID: 9751103, UI: 98421723

Sb Lek 1998;99(1):53-61 [No title available]. [Article in Czech] Vilikus Z, Mareckova H, Janatkova I, Krystufkova O, Barackova M, Boudova L, Brandejsky P, Fucikova T Ustav telovychovneho lekarstvi a Ustav klinicke imunologie 1. lekarske fakulty Univerzity Karlovy, Praha, Czech Republic. zdenek vilikus@medicom.cz Risk factors of coronary artery disease (CAD) between a group of patients suffering of chronic fatigue syndrome (CFS) and a control group of healthy persons (whose exercise activity was not health-limited) were compared. Thirty three patients (27 women, 6 men, average age 39.9 +/- 11.7 years) and the same number of controls matched in age (39.8 +/- 10.3 years), gender and body weight. The Minnesota Questionnaire (by Taylor) and the Compendium of Physical Activities (by Ainsworth) were used to estimate total energetic expenditure in exercise activity as well as in job. The risk factors of CAD in the patients with CFS were not higher than in the control group. Aerobic physical fitness, basic anthropometric data, blood pressure, spectrum of blood lipoproteins, blood uric acid and smoking habits were not different between the compared groups. Patients suffering from CFS had lower total energetic expenditure in exercise activity. Nevertheless, this significant difference in sports activity was not large enough to cause any difference in risk factors of CAD between the CFS patients and the control group. PMID: 9748798, UI: 98420622

Curr Opin Rheumatol 1998 Sep;10(5):446-56 Evolving concepts of diagnosis, pathogenesis, and therapy of Sjogren's syndrome. Fox RI, Tornwall J, Maruyama T, Stern M Division of Rheumatology, Scripps Clinic, La Jolla, CA 92037, USA. Differences in diagnostic criteria for Sjogren's Syndrome (SS) have led to confusion in the research literature and in clinical practice. A particular challenge is the clinical diagnosis of the patients with sicca symptoms, fibromyalgia, chronic fatigue, vague cognitive defects, and a low titer antinuclear antibody. Until recently, many of these patients would have been classified as primary SS using the European criteria. A suggested revision of the European criteria will require inclusion of anti SS-A antibody or characteristic minor salivary gland biopsy, leading to greater agreement between European and San Diego criteria. Recent studies have emphasized that lacrimal and salivary gland flow involves an entire "functioal" unit that includes the mucosal surface (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimatory and salvatory nucleus), efferent neural signals from the brain, and acinal/ductal structures in the gland. Thus, symptoms of dryness or pain can result from interferences with any part of this functional unit. The initiating antigens in SS remain unknown, but immune reactivity against SS-A, SS-B, fodrin, alpha amylase, and carbonic anhydrase have been demonstrated in patients with established disease. The inflammatory process in the gland releases metalloproteinases that alter the relationship of epithelial cells to their matrix, an interaction that is necessary for glandular function and survival. Therapies for SS remain inadequate. In SS patients with immune-mediated extraglandular manifestation (ie, lung, kidney, skin, nerve), the therapeutic approach his similar to systemic lupus erythematosus, although these therapies have relatively little effect on tear or saliva flow. PMID: 9746861, UI: 98418998

J Int Neuropsychol Soc 1998 Sep;4(5):456-66 Attention and verbal learning in patients with Chronic Fatigue Syndrome. Michiels V, Cluydts R, Fischler B Department of Psychology, Free University of Brussels, Belgium. vmichiel@vub.ac.be Former neuropsychological studies with Chronic Fatigue Syndrome (CFS) patients evaluated a broad range of cognitive functions. Several, but not all, reported subtle attentional and memory impairments suggesting possible mild cerebral involvement. In this study, a battery of attentional tests and a verbal memory task were administered to 20 CFS patients and 22 healthy controls (HC) in order to clarify the specific nature of attention and memory impairment in these patients. The results provide evidence for attentional dysfunction in patients with CFS as compared to HC. CFS patients performed more poorly on a span test measuring attentional capacity and working memory. Speeded attentional tasks with a more complex element of memory scanning and divided attention seem to be a sensitive measure of reduced attentional capacity in these patients. Focused attention, defined as the ability to attend to a single stimulus while ignoring irrelevant stimuli, appears not to be impaired. CFS patients were poorer on recall of verbal information across learning trials, and poor performance on delayed recall may be due to poor initial learning and not only to a retrieval failure. PMID: 9745235, UI: 98417756

Med Sci Sports Exerc 1998 Sep;30(9):1345-8 The case history of an elite ultra-endurance cyclist who developed chronic fatigue syndrome. Rowbottom DG, Keast D, Green S, Kakulas B, Morton AR Department of Human Movement, University of Western Australia, Nedlands, Australia. An elite ultra-endurance athlete, who had previously undergone physiological and performance testing, developed chronic fatigue syndrome (CFS). An incremental cycling exercise test conducted while he was suffering from CFS indicated decreases in maximum workload achieved (Wmax; -11.3%), the maximum oxygen uptake (VO2max; -12.5%), and the anaerobic threshold (AT; -14.3%) compared to pre-CFS data. A third test conducted after the athlete had shown indications of significant improvement in his clinical condition revealed further decreases in Wmax (-7.9%), VO2max (-10.2%) and AT (-8.3%). These data, along with submaximal exercise data and muscle biopsy electron microscopic analyses, suggest that the performance decrements were the result of detraining, rather than an impairment of aerobic metabolism due to CFS per se. These data may be indicative of central, possibly neurological, factors influencing fatigue perception in CFS sufferers. PMID: 9741601, UI: 98412632

Compr Ther 1998 Aug;24(8):357-63 Chronic fatigue syndrome: Its cause and a strategy for management. McCluskey DR Queens University of Belfast, Royal Victoria Hospital, Ireland. This article describes the features of chronic fatigue syndrome and, by analysis of the many clinical paradoxes which it manifests, attempts to give a unifying explanation of the cause of the disorder and a strategy for management. PMID: 9740980, UI: 98413414

J Med Assoc Thai 1998 Sep;81(9):717-21 Pentazocine-induced fibrous myopathy and localized neuropathy. Sinsawaiwong S, Phanthumchinda K Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. A 47 year-old woman who had a 4-year history of intramuscular pentazocine injections in the lower extremities, developed gradual stiffness and weakness of the lower extremities. The thigh and buttock muscles were "wooden-hard" on palpation. The skin was hard, shiny and hairless. Associated clinical and electrophysiological polyradiculopathy and multiple mononeuropathy of the lower extremities were observed. Imaging studies showed calcification and fibrosis of the involved muscles. Muscle biopsy revealed fibrous myopathy. Caution in longterm usage and early recognition of pentazocine toxicity as a neuromuscular complication are important in order to prevent irreversible drug-induced fibrous myopathy and localized neuropathy. PMID: 9737132, UI: 98408345

Altern Med Rev 1998 Aug;3(4):271-80 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Birdsall TC 73541.2166@compuserve.com 5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia. Publication Types: Review Review, tutorial PMID: 9727088, UI: 98404751

J Allergy Clin Immunol 1998 Aug;102(2):222-30 Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables. Borish L, Schmaling K, DiClementi JD, Streib J, Negri J, Jones JF Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver 80206, USA. BACKGROUND: We investigated a role for allergic inflammation and psychologic parameters in the development of chronic fatigue syndrome (CFS). METHODS: The design was a comparison between subjects with CFS and age- and sex-matched control cohorts. Studies were performed on CFS subjects (n = 18) and control cohorts consisting of normal subjects (n = 11), allergic subjects (n = 14), and individuals with primary depression (n = 12). We quantified cytokines at baseline as cell-associated immunoreactive peptides and as transcripts evaluated by means of semiquantitative RNA-based polymerase chain reactions. Psychologic evaluations included administration of the Diagnostic Interview Schedule, the Structured Clinical Interview, and the Symptom Checklist 90-Revised. RESULTS: Increases in tumor necrosis factor (TNF)-alpha were identified in individual subjects with CFS (50.1 +/- 14.4 pg TNF-alpha per 10(7) peripheral blood mononuclear cells [PBMCs]; mean +/- SEM) and allergic subjects (41.6 +/- 7.6) in comparison with normal subjects (13.1 +/- 8.8) (P < .01 and P < .05, respectively). Similar trends were observed for interferon (IFN)-alpha in allergic subjects (3.0 +/- 1.7 pg/10(7) PBMCs) and subjects with CFS (6.4 +/- 3.4) compared with normal subjects (1.9 +/- 1.4). A significant increase (P < .05) in TNF-alpha transcripts was demonstrated between subjects with CFS and depressed subjects. In contrast to these proinflammatory cytokines, both subjects with CFS (2.6 +/- 1.8 pg/10(7) PBMCs) and allergic subjects (3.4 +/- 2.8) were associated with a statistically significant (P < .01) decrease in IL-10 concentrations compared with normal subjects (60.2 +/- 18.2). As shown in other studies, most of our subjects with CFS were allergic (15 of 18) and therefore presumably demonstrated cytokine gene activation on that basis. The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-alpha (from 2.1 +/- 1.2 to 14.2 +/- 4.5 pg/107 PBMCs; P < .05) but no further modulation of TNF-alpha or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-alpha (from 2.5 +/- 1.0 to 21.9 +/- 7.8; P < .05) and occurred at times of seasonal exposures to allergens. This linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-alpha with the increase in CFS symptoms. The close association between atopy and CFS led us to speculate that CFS may arise from an abnormal psychologic response to the disordered expression of these proinflammatory and antiinflammatory cytokines. Psychologic variables were predictive of immune status within the CFS sample (65.9% of the variance in immune status; F (3,10) = 6.44, P < .05). Specifically, the absence of a personality disorder but greater endorsement of global psychiatric symptoms was predictive of immune activation. CONCLUSIONS: Most of our subjects with CFS were allergic, and the CFS and allergy cohorts were similar in terms of their immune status. However, the CFS subjects could be discriminated by the distinct psychologic profiles among subjects with and without immune activation. We propose that in at least a large subgroup of subjects with CFS who had allergies, the concomitant influences of immune activation brought on by allergic inflammation in an individual with the appropriate psychologic profile may interact to produce the symptoms of CFS. In a psychologically predisposed individual, symptoms associated with allergic inflammation are recognized as illness. PMID: 9723665, UI: 98389058

Psychol Med 1998 Jul;28(4):957-65 Lower serum activity of prolyl endopeptidase in fibromyalgia is related to severity of depressive symptoms and pressure hyperalgesia. Maes M, Libbrecht I, Van Hunsel F, Lin AH, Bonaccorso S, Goossens F, De Meester I, De Clerck L, Biondi M, Scharpe S, Janca A Department of Medical Biochemistry, University of Antwerp, Belgium. BACKGROUND: The aims of the present study were to examine serum activities of peptidases, i.e. prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), in patients with fibromyalgia and to examine the effects of subchronic treatment with sertraline on these variables. METHOD: Serum PEP and DPP IV activity were measured in 28 normal volunteers and 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Tenderness at tender points was evaluated by means of dolorimetry. Fibromyalgia patients had repeated measurements of serum PEP and DPP IV both before and after repeated administration of sertraline or placebo for 12 weeks. RESULTS: Patients with fibromyalgia had significantly lower serum PEP activity than normal volunteers. There were significantly negative correlations between serum PEP activity and severity of pressure hyperalgesia and the non-somatic, cognitive symptoms of the Hamilton Depression Rating Scale. Fibromyalgia patients with severe pressure hyperalgesia had significantly lower PEP activity than normal controls and fibromyalgia patients with less severe hyperalgesia. Fibromyalgia patients with severe non-somatic depressive symptoms had significantly lower serum PEP activity than normal volunteers. There were no significant changes in serum DPP IV activity in fibromyalgia. There were no significant effects of repeated administration of sertraline on serum PEP and DPP IV activity in patients with fibromyalgia. CONCLUSIONS: The results show that fibromyalgia, and aberrant pain perception and depressive symptoms in fibromyalgia are related to lower serum PEP activity. It is hypothesized that lower serum PEP activity may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides. PMID: 9723150, UI: 98390592

Int J Sports Med 1998 Jul;19 Suppl 3:S205-9; discussion S209-11 Future directions in exercise and immunology: regulation and integration. Mackinnon LT Department of Human Movement Studies, The University of Queensland, Australia. Although it is difficult to predict future directions in a rapidly expanding field such as exercise immunology, recently published research along with that presented at this Symposium allow us to ask some key questions which may point to new directions: 1) Are athletes immunocompromised? Athletes are not clinically immunodeficient, yet endurance athletes are at increased risk of illness. Long-term prospective studies are needed to understand the relationship between infection, training variables and immune parameters. 2) Is downregulation of nonspecific immunity beneficial or harmful? In athletes, neutrophils appear to be downregulated, and this may alter resistance to illness. Alternatively, neutrophils are mediators of tissue damage during inflammation. Downregulation of neutrophil function may be protective by limiting chronic inflammation. In athletes, mild immunosuppression may reflect a compromise between the body's attempts to limit inflammation while maintaining immune function. 3) What mediates communication between events in skeletal muscle and the immune system? Leukocyte mobility is affected by metabolic and mechanical factors during exercise. Exercise increases cytokine levels in damaged skeletal muscle and expression of adhesion molecules. Future work is likely to focus on the role of cytokines and adhesion molecules in mediating exercise-induced changes in leukocyte mobility. 4) Can exercise training provide a "countermeasure" against immunosuppressive events? Moderate exercise training may have a role in stimulating the immune system during certain diseases (e.g., HIV-infection), immune dysfunction (e.g., chronic fatigue syndrome) or reduced responsiveness (e.g. aging, spaceflight). It is also likely that future study will apply molecular biology techniques to further identify mechanisms by which exercise influences immune function. PMID: 9722286, UI: 98387741

J Psychosom Res 1998 Jul;45(1 Spec No):85-91 Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome. Stores G, Fry A, Crawford C University Section, Park Hospital for Children, Oxford, UK. To provide objective information about sleep physiology in young people with chronic fatigue syndrome (CFS), home polysomnography (PSG) was performed on 18 teenagers, aged 11-17 years, in whom CFS had been diagnosed according to internationally accepted criteria. The results were compared with those for healthy controls matched individually for gender and age. Compared with controls, CFS subjects showed significantly higher levels of sleep disruption by both brief and longer awakenings. Disruption of sleep in this way could at least contribute to the daytime symptoms of young people with CFS. The underlying cause of the disruption needs to be considered in each individual case. Further research is required to clarify the relative contribution of this neurobiological aspect of CFS in young people. PMID: 9720858, UI: 98385812

J Psychosom Res 1998 Jul;45(1 Spec No):77-83 Illness beliefs and treatment outcome in chronic fatigue syndrome. Deale A, Chalder T, Wessely S Department of Psychological Medicine, Kings College Hospital, and Institute of Psychiatry, London, UK. Longitudinal studies have shown that physical illness attributions are associated with poor prognosis in chronic fatigue syndrome (CFS). Speculation exists over whether such attributions influence treatment outcome. This study reports the effect of illness beliefs on outcome in a randomized controlled trial of cognitive-behavior therapy versus relaxation. Causal attributions and beliefs about exercise, activity, and rest were recorded before and after treatment in 60 CFS patients recruited to the trial. Physical illness attributions were widespread, did not change with treatment, and were not associated with poor outcome in either the cognitive-behavior therapy group or the control group. Beliefs about avoidance of exercise and activity changed in the cognitive behavior therapy group, but not in the control group. This change was associated with improved outcome. These findings suggest that physical illness attributions are less important in determining outcome (at least in treatment studies) than has been previously thought. In this study, good outcome is associated with change in avoidance behavior, and related beliefs, rather than causal attributions. PMID: 9720857, UI: 98385811

J Psychosom Res 1998 Jul;45(1 Spec No):67-76 Longitudinal changes associated with improvement in chronic fatigue patients. Russo J, Katon W, Clark M, Kith P, Sintay M, Buchwald D Department of Psychiatry & Behavioral Sciences, Harborview Medical Center, University of Washington, Seattle 98104, USA. jerusso@u.washington.edu Tertiary care patients with chronic fatigue were followed for 2.5 years to determine if changes in physical and psychological status were associated with improvements in chronic fatigue, physical functioning, and return to work. Results indicated that improvement in psychological symptoms, DSM-III-R disorders, physical examination signs, and changes in whether the patient continued to meet criteria for chronic fatigue syndrome (CFS) were associated with recovery from fatigue, improved functioning, and return to work. Patients who never met CFS criteria or only met criteria at the initial assessment, reported improved physical functioning. Patients whose psychiatric disorders and physical examination signs were still present at a mean follow-up time of 2.5 years were more likely to have persistent fatigue and work disability. Loss of physical examination signs was a significant independent predictor of improved functioning and return to work. These results suggest that psychiatric status, as well as physical status, are associated with recovery from chronic fatigue. PMID: 9720856, UI: 98385810

J Psychosom Res 1998 Jul;45(1 Spec No):39-51 Coping and adaptive outcome in chronic fatigue syndrome: importance of illness cognitions. Heijmans MJ Department of Clinical and Health Psychology, Utrecht University, The Netherlands. M.Heijmans@fsw.ruu.nl In this study, the relations between illness representations, coping behavior, and adaptive outcomes in chronic fatigue syndrome (CFS) patients (N=98) were examined. Following Leventhal's self-regulation model, it was hypothesized that illness representations would be directly related to coping and, via coping, to adaptive outcome. The results showed patients who considered their illness to be a serious condition, who believed that they had no control over their illness, who saw little possibility for cure, and who believed their illness to have serious consequences to cope with their illness in a passive way, report higher levels of impairment in physical and social functioning and report greater problems in mental health and vitality. A series of regression analyses showed illness representations to be stronger predictors of adaptive outcome than coping scores. The implications of these findings for the treatment of CFS patients are discussed. PMID: 9720854, UI: 98385808

Eur Rev Med Pharmacol Sci 1998 Nov-Dec;1(6):193-5 Three cases of dermatomyositis erroneously diagnosed as "chronic fatigue syndrome". Fiore G, Giacovazzo F, Giacovazzo M VI Cattedra di Medicina Interna, Universita La Sapienza, Roma, Italy. The authors report three cases of dermatomyositis, which ha been erroneously diagnosed as "chronic fatigue syndrome" due to the presence of elevated titers of serum anti-Epstein Barr antibodies. PMID: 9718854, UI: 98384992

Clin Endocrinol (Oxf) 1998 Jun;48(6):733-7 The low dose ACTH test in chronic fatigue syndrome and in health. Scott LV, Medbak S, Dinan TG Department of Psychiatry, Trinity College Medical School, Dublin, Eire. OBJECTIVE: A number of dynamic tests of the hypothalamic-pituitary-adrenal axis provide evidence for a mild central adrenal insufficiency in chronic fatigue syndrome (CFS). The 1 microgram adrenocorticotropin (ACTH) test has been proposed to be more sensitive than the standard 250 micrograms ACTH test in the detection of subtle pituitary-adrenal hypofunctioning. We aimed to establish whether the 1 microgram ACTH test would support such a dysregulation in CFS, and also, given the relative novelty of this test in clinical practice and the uncertainty with regard to appropriate cut-off values for normality, to compare our healthy volunteer data with those of previous studies. PATIENTS AND DESIGN: Twenty subjects with CFS, diagnosed according to Centres for Disease Control and Prevention criteria, were compared with 20 healthy volunteer subjects. All participants underwent a 1 microgram ACTH test beginning at 1400 h. Plasma samples for cortisol estimation were drawn at 0, +30 and +40 min. RESULTS: Baseline cortisol values did not differ between CFS patients and healthy subjects. The delta cortisol (maximum increment from baseline) value was significantly lower in the CFS than the volunteer group (P < 0.05). Comparison of the +30 min cortisol values revealed no significant differences. Using an incremental cortisol of 250 nmol/l as an arbitrary cutoff point, two (10%) of the healthy subjects and nine (45%) of the CFS subjects failed the test on this basis (chi 2 = 4.3, df = 38, P < 0.05). CONCLUSIONS: This study provides further evidence for a subtle pituitary-adrenal insufficiency in subjects with chronic fatigue syndrome compared to healthy volunteers. Disparities between our healthy volunteer data and those of other groups using the 1 microgram ACTH test suggest that the test may not be as reliable as previously indicated. PMID: 9713562, UI: 98379184

Aust N Z J Psychiatry 1998 Aug;32(4):523-7 Chronic fatigue syndrome: an immunological perspective. Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia. OBJECTIVE: The aim of this study is to review research examining an immunological basis for chronic fatigue syndrome (CFS) and to discuss how a disturbance in immunity could produce central nervous system (CNS)-mediated symptoms. METHOD: Data relevant to the hypothesis that abnormal cytokine release plays a role in the pathogenesis of CFS are reviewed as well as recent evidence relating to potential mechanisms by which immune products may enter the brain and produce a disturbance in CNS processes. RESULTS: Examinations of cytokine levels in patients with CFS have produced inconclusive results. Recent evidence suggests that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms. CONCLUSION: Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines. This possibility is discussed in the context of unresolved issues in the pathogenesis of CFS. PMID: 9711366, UI: 98377225

J Clin Immunol 1998 Jul;18(4):291-8 Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. Cannon JG, Angel JB, Abad LW, O'Grady J, Lundgren N, Fagioli L, Komaroff AL Department of Medicine, New England Medical Center, Boston, Massachusetts, USA. jgc2@psu.edu This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion. For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively). These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS. PMID: 9710746, UI: 98376605

Psychosom Med 1998 Jul-Aug;60(4):394-401 Sociosomatics and illness in chronic fatigue syndrome. Ware NC Department of Social Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. nware@warren.med.harvard.edu OBJECTIVE: This study examines social processes that construct the course of chronic illness. Specifically, it identifies and describes mechanisms that constitute the process of role constriction in employment for individuals with chronic illness. METHOD: Sixty-six persons meeting the Centers for Disease Control case definition of chronic fatigue syndrome (CFS) participated in a longitudinal study involving three waves of data collection over 3 years. Qualitative and quantitative methods were combined in the research, which included face-to-face semistructured interviews, telephone interviews, and self-report questionnaires. Materials presented in this study are drawn principally from the Year 1 face-to-face and telephone interviews. RESULTS: When patterns of symptoms and of the illness course in CFS intersect with work requirements, they impede performance and place ill individuals at risk for job loss. Persons with CFS devise and implement specific strategies to resist role constriction and remain in the work force. CONCLUSIONS: Role constriction is a social process of marginalization in chronic illness. Opposing forces of marginalization and resistance define the social course in chronic illness and suggest that chronicity can be thought of as a marginalized position in social space. PMID: 9710284, UI: 98374058

Rev Belge Med Dent 1997;52(4):115-23 [Etiologic factors in temporomandibular joint disorders and pain]. [Article in French] De Laat A Departement d'Odontologie, Universite Catholique de Leuven. Parallel to the construction of better classifications and the identification of subgroups of temporomandibular disorders, an important development has taken place in research concerning its etiology. The etiological factors implied in muscle problems refer to more generalised disorders as myofascial pain syndrome and fibromyalgia. The role of occlusal and articular factors has been brought down to realistic proportions, indicating a minor contribution. Similarly, doubt has arisen concerning the existence of a vicious cycle of pain/spasm/pain. With regard to internal derangements, emphasis has been put on the high prevalence in an otherwise normal population and the fluctuating character of the symptom. Also here, developments point towards constitutional and systemic factors, more than local influences. Trauma, however, seems to play an increasing role. The development of osteoarthrosis has been studied more in depth revealing local processes of inflammation, neurogenic inflammation and the existence of specific markers which might be important in the future. The relationship between disc derangement and the development of osteoarthrosis remains unclear. Publication Types: Review Review, tutorial PMID: 9709799, UI: 98375564

Neurosci Lett 1998 Jul 10;250(3):205-7 Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia. Morris V, Cruwys S, Kidd B Bone and Joint Research Unit, St Bartholomew's and Royal London Hospital School of Medicine, UK. In this study, capsaicin-induced secondary hyperalgesia was assessed as a marker of abnormal nociceptive processing in patients with fibromyalgia (FM). The area of mechanical secondary hyperalgesia induced by a standard solution of capsaicin placed on the volar forearm was measured in ten patients with FM and the results compared to those obtained in ten patients with rheumatoid arthritis (RA) and ten normal subjects. The area of secondary hyperalgesia was found to be substantially increased in both the FM and RA groups compared with controls. In the FM group the area of hyperalgesia correlated with the overall pain score and with the joint tenderness score. The results suggest that in FM there is enhanced sensitivity of nociceptive neurones at a spinal level, thereby supporting the concept of a generalised disturbance of pain modulation in this disorder. PMID: 9708868, UI: 98372599

Neuropsychobiology 1998;38(1):13-8 Serum neopterin and somatization in women with chemical intolerance, depressives, and normals. Bell IR, Patarca R, Baldwin CM, Klimas NG, Schwartz GE, Hardin EE Department of Psychiatry, Psychology, Family and Community Medicine, University of Arizona Health Sciences Center, and the Department of Psychiatry, Tucson Veterans Affairs Medical Center, Tucson, Ariz., USA. The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders. Publication Types: Clinical trial Controlled clinical trial PMID: 9701717, UI: 98369085

Acta Odontol Scand 1998 Jun;56(3):129-34 Effect of local glucocorticoid injection on masseter muscle level of serotonin in patients with chronic myalgia. Ernberg M, Hedenberg-Magnusson B, Alstergren P, Kopp S Department of Clinical Oral Physiology, Faculty of Odontology, Karolinska Institute, Huddinge, Sweden. The aim of this study was to compare the effects on the level of serotonin (5-HT) in the masseter muscle by intramuscular glucocorticoid (GC) administration in patients with fibromyalgia (FM) and localized myalgia (LM), as well as to determine associated changes in pain, tenderness, and microcirculation. The study comprised 22 patients with pain and tenderness in the masseter muscle region. Ten patients (all women) had FNI, and 12 (1 man and 11 women) had LM involving the temporomandibular system. The patients were examined clinically and by microdialysis at 2 visits 2-3 weeks apart and received local glucocorticoid treatment at the first visit. The ratio (S1/S2) between the initial level of 5-HT (S1) and steady state level (S2) was used as a relative measure of the intramuscular release of 5-HT. This ratio decreased significantly after treatment in the FM group. In the FM group there was also a negative correlation regarding changes between visits of 5-HT and changes of intramuscular temperature. In the LM group there was a negative correlation regarding changes between visits of 5-HT and changes of pressure pain threshold and pressure pain tolerance level. This study indicates that there is a reduction of the ratio between initial 5-HT and steady state level in the painful masseter muscle after intramuscular GC administration to FM patients, a reduction not present in the LM patients. In addition, 5-HT seems to be involved in the modulation of local muscle microcirculation in FM patients and in hyperalgesia in LM patients. PMID: 9688220, UI: 98351506

West J Nurs Res 1998 Aug;20(4):501-7 Balancing ethical quandaries with scientific rigor: Part 2. Pallikkathayil L, Crighton F, Aaronson LS University of Kansas School of Nursing, USA. Traditional ethical concerns in research tend to focus on serious misconduct such as fabricating data and gross violations of informed consent. In this two-part article, we focused on some of the less serious and more subtle ethical quandaries, inherent and common in most social science research. It is our thesis that these issues are important and warrant more attention and careful thought than they have been accorded in the scientific literature and, perhaps, by investigators at large. In Part 2, we provided examples of how we, and others, dealt with some of these issues in actual studies. However, we also must emphasize the individual and reflective nature of confronting ethical issues in research. We found many benefits in using a team approach to address ethical dilemmas during implementation of our studies. Doing so kept everyone honest with themselves and each other, shared the burden of responsibility among team members for the decisions made, maximized the use of team members' strengths, and led to much better resolutions of the issues from both a scientific and an ethical perspective. Maintaining scientific rigor while balancing and deliberating about the ethical implications of decisions is a challenge for all research teams. It requires learning how to be vigilant and responsive when faced with the many subtle, but ever-present, scientific and ethical quandaries encountered when doing what is often assumed to be nonthreatening social research. There are no fixed, prescriptive rules for what to do in every study. Rather, a reflective process, considering the specific issues of each unique study, is required. PMID: 9686526, UI: 98351145

Pediatrics 1998 Aug;102(2 Pt 1):360-6 Course and outcome of chronic fatigue in children and adolescents. Krilov LR, Fisher M, Friedman SB, Reitman D, Mandel FS Department of Pediatrics, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA. PURPOSE: To describe the epidemiology, symptoms, and psychosocial characteristics of children and adolescents evaluated in a chronic fatigue program and determine the course and outcome of the syndrome in these patients. METHODS: During the summer of 1994, chart review was performed for the 58 patients evaluated between 1990 and 1994 and a telephone follow-up was conducted with 42 of the 58 families. Patients were predominantly female (71%) and white (94%), with 50% between the ages of 7 and 14 years and 50% between the ages of 15 and 21 years (mean age 14.6 years). RESULTS: At time of presentation, 50% of patients had been fatigued for 1 to 6 months and 50% had been fatigued for 7 to 36 months. Sixty percent indicated the fatigue had begun with an acute illness and 60% had a history of allergies. Most commonly reported symptoms were fatigue (100%), headache (74%), sore throat (59%), abdominal pain (48%), fever (36%), and difficulties with concentration and/or memory (33%). Most patients had a worsening of school performance and a decrease in social activities. On follow-up, there was significant improvement in many patients during the summer after the first visit, with continued improvement in most patients during the second and third years. At time of the follow-up telephone call, 43% of families considered their child "cured" and 52% considered their child "improved," whereas only 5% considered their child to be "the same." Statistical analyses demonstrated no demographic or clinical factors that distinguished between those who did or did not participate in the follow-up study, or between those who did or did not do well on follow-up. CONCLUSIONS: These data demonstrate that children and adolescents with chronic fatigue have a syndrome that is similar to that described in adults, but that the syndrome differs in several ways, most specifically, presentation earlier in the course of the illness and a more optimistic outcome. PMID: 9685439, UI: 98352248

Postgrad Med J 1998 Apr;74(870):229-32 Phosphate diabetes in patients with chronic fatigue syndrome. De Lorenzo F, Hargreaves J, Kakkar VV Beatrice Research Centre, London, UK. Phosphate depletion is associated with neuromuscular dysfunction due to changes in mitochondrial respiration that result in a defect of intracellular oxidative metabolism. Phosphate diabetes causes phosphate depletion due to abnormal renal re-absorption of phosphate be the proximal renal tubule. Most of the symptoms presented by patients with phosphate diabetes such as myalgia, fatigue and mild depression, are also common in patients with chronic fatigue syndrome, but this differential diagnosis has not been considered. We investigated the possible association between chronic fatigue syndrome and phosphate diabetes in 87 patients who fulfilled the criteria for chronic fatigue syndrome. Control subjects were 37 volunteers, who explicitly denied fatigue and chronic illness on a screening questionnaire. Re-absorption of phosphate by the proximal renal tubule, phosphate clearance and renal threshold phosphate concentration were the main outcome measures in both groups. Of the 87 patients with chronic fatigue syndrome, nine also fulfilled the diagnostic criteria for phosphate diabetes. In conclusion, we report a previously undefined relationship between chronic fatigue syndrome and phosphate diabetes. Phosphate diabetes should be considered in differential diagnosis with chronic fatigue syndrome; further studies are needed to investigate the incidence of phosphate diabetes in patients with chronic fatigue syndrome and the possible beneficial effect of vitamin D and oral phosphate supplements. PMID: 9683977, UI: 98348602

Clin Immunol Immunopathol 1998 Jul;88(1):96-104 Dysfunction of natural killer activity in a family with chronic fatigue syndrome. Levine PH, Whiteside TL, Friberg D, Bryant J, Colclough G, Herberman RB National Cancer Institute, Bethesda, Maryland, 20892, USA. A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer. PMID: 9683556, UI: 98350101

Altern Ther Health Med 1998 Mar;4(2):67-70 A pilot study of cognitive behavioral therapy in fibromyalgia. Singh BB, Berman BM, Hadhazy VA, Creamer P University of Maryland School of Medicine, Baltimore, USA. bsingh@compmed.ummc.ab.umd.edu BACKGROUND: Fibromyalgia is a syndrome characterized by widespread musculoskeletal pain and multiple tender points as well as high levels of self-reported disability and poor quality of life. OBJECTIVES: In this pilot study, a mind-body approach (cognitive-behavioral therapy) was tested that has been successful in treating chronic back pain patients to determine whether it would improve function, decrease perceived pain, and improve mood state for fibromyalgia patients. PARTICIPANTS: 28 patients recruited from the greater Baltimore area. INTERVENTION: Eight weekly sessions, 2 1/2 hours each, with three components: an educational component focusing on the mind-body connection, a portion focusing on relaxation response mechanisms (primarily mindfulness meditation techniques), and a qigong movement therapy session. MAIN OUTCOME MEASURES: Data collection instruments were the Fibromyalgia Impact Questionnaire, the Health Assessment Questionnaire, the Beck Depression Inventory, the Coping Strategies Questionnaire, the helplessness subscale of the Arthritis Attitudes Index, the Medical Outcomes Study Short Form General Health Survey, and a double-anchored 100-mm visual analog scale to assess sleep. RESULTS: Twenty patients completed the study. Standard outcome measures showed significant reduction in pain, fatigue, and sleeplessness; and improved function, mood state, and general health following an 8-week intervention. CONCLUSION: A mind-body intervention including patient education, meditation techniques, and movement therapy appears to be an effective adjunctive therapy for patients with fibromyalgia. PMID: 9682514, UI: 98347436

HNO 1998 Jun;46(6):583-6 [Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss]. [Article in German] Heller U, Becker EW, Zenner HP, Berg PA HNO-Klinik, Universitat Tubingen. Immunoserological assays of patients with sudden deafness and progressive hearing losses have revealed the presence of different antibodies, leading to the assumption that immunological processes may be involved. Recent investigations have demonstrated that these patients have phospholipid antibodies that can cause venous or arterial vasculopathies. In the present study we analyzed the incidence of these antibodies in patients with inner ear disorders. Sera of 55 patients with sudden deafness and 80 patients with progressive hearing loss were tested. Phospholipid antibodies were demonstrable in 49% of the patients with sudden hearing loss and 50% of the patients with progressive hearing loss. Serotonin and ganglioside antibodies were found in 53% of the patients with sudden hearing loss and 63% of the patients with progressive hearing loss. Since these three antibodies are also frequently found in patients with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS), 28 of the patients studied displayed symptoms typical for these disorders, including fatigue, myalgia, arthralgia, depressions, sicca symptoms and diarrhea. We now recommend questioning patients suffering from inner ear disorders for symptoms typical for FMS or CFS, since these diseases are often closely related to inner ear disorders. If symptoms are present, antibodies should be tested against phospholipids, serotonin and gangliosides. If present, the antibodies are diagnostic for each syndrome. Additionally these immunologic and serologic findings show that these antibodies may play a role in the etiology of hearing loss disorders. Comments: Comment in: HNO 1998 Jun;46(6):565-6 PMID: 9677490, UI: 98342454

J Rheumatol 1998 Jul;25(7):1374-81 Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain. Griep EN, Boersma JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER Research Department, Jan van Breemen Institute, Amsterdam, The Netherlands. OBJECTIVE: We suggested fibromyalgia (FM) is a disorder associated with an altered functioning of the stress-response system. This was concluded from hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin induced hypoglycemia in patients with FM. In this study, we tested the validity and specificity of this observation compared to another painful condition, low back pain. METHODS: We recruited 40 patients with primary FM (F:M 36:4), 28 patients (25:3) with chronic noninflammatory low back pain (LBP), and 14 (12:2) healthy, sedentary controls. A standard 100 microg CRH challenge test was performed with measurement of ACTH and cortisol levels at 9 time points. They were also subjected to an overnight dexamethasone suppression test, followed by injection of synthetic ACTH1-24. At 9 AM, the patients divided in 2 groups, received either 0.025 or 0.100 microg ACTH/kg body weight to test for adrenocortical sensitivity. Basal adrenocortical function was assessed mainly by measurement of 24 h urinary excretion of free cortisol. RESULTS: Compared to the controls, the patients with FM displayed a hyperreactive ACTH release in response to CRH challenge (ANOVA interaction effect p = 0.001). The mean ACTH response of the patients with low back pain appeared enhanced also, but to a significantly lesser extent (p = 0.02 at maximum level) than observed in the patients with FM. The cortisol response was the same in the 3 groups. Following dexamethasone intake there were 2 and 4 nonsuppressors in the FM and LBP groups, respectively. The very low and low dose of exogenous ACTH1-24 evoked a dose and time dependent cortisol response, which, however, was not significantly different between the 3 groups. The 24 h urinary free cortisol levels were significantly lower (p = 0.02) than controls in both patient groups; patients with FM also displayed significantly lower (p < 0.05) basal total plasma cortisol than controls. CONCLUSION: The present data validate and substantiate our preliminary evidence for a dysregulation of the HPA axis in patients with FM, marked by mild hypocortisolemia, hyperreactivity of pituitary ACTH release to CRH, and glucocorticoid feedback resistance. Patients with LBP also display hypocortisolemia, but only a tendency toward the disrupted HPA features observed in the patients with FM. We propose that a reduced containment of the stress-response system by corticosteroid hormones is associated with the symptoms of FM. PMID: 9676772, UI: 98339394

J Rheumatol 1998 Jul;25(7):1369-73 Ethnocultural and educational differences in Israeli women correlate with pain perception in fibromyalgia. Neumann L, Buskila D Epidemiology Department, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel. OBJECTIVE: To compare the clinical features of patients with fibromyalgia (FM) in 2 ethnic groups in Israel. METHODS: One hundred women with FM participated in the study; 70 were of Sephardic (Mediterranean) origin and 30 of Ashkenazic (European-American) origin. Assessment of FM related symptoms, tenderness, quality of life, and physical functioning was conducted in all subjects. Analysis of covariance and multivariate regression were performed to study the association between these measures and ethnicity, controlling for age and education. RESULTS: Sephardic patients with FM reported more frequent and more severe symptoms than Ashkenazic patients. They had higher point counts and decreased quality of life. When the patients were divided into 2 age groups (age 45 being the cutoff point), the differences were observed only among the older subjects, most of whom were immigrants. Sephardic older patients had significantly higher point counts than Ashkenazic patients, and lower tenderness thresholds. They reported significantly higher levels of pain, fatigue, and stiffness, and were less satisfied with their life. However, these differences observed between the 2 ethnic groups in the univariate data analysis disappeared when age and education were jointly controlled in multivariate regression analysis. Age had significantly contributed to the variation in the point count, the reported pain, and physical functioning. Education made a significant contribution in explaining the point count, quality of life, pain, and fatigue. CONCLUSION: Education, rather than ethnic identity, has been found to be an important factor in clinical features of FM. Future studies should include ethnocultural and educational assessment, especially in countries with high immigration rates and diverse ethnic groups, such as the USA and Canada. PMID: 9676771, UI: 98339393

JAMA 1998 Jul 15;280(3):264-6 Reviewing the reviews: the example of chronic fatigue syndrome. Joyce J, Rabe-Hesketh S, Wessely S Institute of Psychiatry, King's College School of Medicine, London, England. OBJECTIVE: To test the hypothesis that the selection of literature in review articles is unsystematic and is influenced by the authors' discipline and country of residence. DATA SOURCES: Reviews in English published between 1980 and March 1996 in MEDLINE, EMBASE (BIDS), PSYCHLIT, and Current Contents were searched. STUDY SELECTION: Reviews of chronic fatigue syndrome (CFS) were selected. Articles explicitly concerned with a specialty aspect of CFS and unattributed, unreferenced, or insufficiently referenced articles were discarded. DATA EXTRACTION: Record of data sources in each review was noted as was the departmental specialty of the first author and his or her country of residence. The references cited in each index paper were tabulated by assigning them to 6 specialty categories, by article title, and by assigning them to 8 categories, by country of journal publication. DATA SYNTHESIS: Of 89 reviews, 3 (3.4%) reported on literature search and described search method. Authors from laboratory-based disciplines preferentially cited laboratory references, while psychiatry-based disciplines preferentially cited psychiatric literature (P = .01). A total of 71.6% of references cited by US authors were from US journals, while 54.9% of references cited by United Kingdom authors were published in United Kingdom journals (P = .001). CONCLUSION: Citation of the literature is influenced by review authors' discipline and nationality. PMID: 9676676, UI: 98339298

Rheumatol Int 1998;18(1):35-6 Pain treatment of fibromyalgia by acupuncture. Sprott H, Franke S, Kluge H, Hein G The lack of objective parameters makes the measurement of pain and the efficacy of pain treatment in patients with chronic pain very difficult. We performed acupuncture therapy in fibromyalgia patients and established a combination of methods to objectify pain measurement before and after therapy. The parameters corresponded to patients' self-report. Twenty-nine fibromyalgia patients as defined by ACR-criteria (25 women, 4 men) with a mean age of 48.2 +/- 2.0 years and a mean disease duration of 6.1 +/- 1.0 years participated in the study. Pain levels and positive tender points were assessed using the visual analogue scale (VAS, i.e., range 0-100 mm) and dolorimetry. Serotonin and substance P levels in serum and the serotonin concentration in platelets were measured concomitantly. During acupuncture therapy no analgesic medication was allowed. The VAS scores decreased from 64.0 +/- 3.4 mm before therapy to 34.5 +/- 4.3 mm after therapy (P < 0.001). Dolorimetry revealed a decreased number of tender points after therapy from 16.0 +/- 0.6 to 11.8 +/- 1.0, P < 0.01. Serotonin levels decreased from 715.8 +/- 225.8 micrograms/10(12) platelets to 352.4 +/- 47.9 micrograms/10(12) platelets (P < 0.01), whereas the serum concentration increased from 134.0 +/- 14.3 ng/ml to 171.2 +/- 14.6 ng/ml (P < 0.01). Substance P levels in serum increased from 43.4 +/- 3.5 pg/ml to 66.9 +/- 8.8 pg/ml (P < 0.01). Acupuncture treatment of patients with fibromyalgia was associated with decreased pain levels and fewer positive tender points as measured by VAS and dolorimetry. This was accompanied by decreased serotonin concentration in platelets and an increase of serotonin and substance P levels in serum. These results suggest that acupuncture therapy is associated with changes in the concentrations of pain-modulating substances in serum. The preliminary results are objective parameters for acupuncture efficacy in patients with fibromyalgia. Publication Types: Letter PMID: 9672997, UI: 98336868

Rheumatol Int 1998;18(1):17-20 Clinical diagnosis found in patients with Raynaud's phenomenon: a multicentre study. Grassi W, De Angelis R, Lapadula G, Leardini G, Scarpa R Clinica Reumatologica, Ospedale A. Murri, Jesi, Italy. A multicentre observational study was conducted in order to detect the major clinical diagnosis found in 761 patients with Raynaud's phenomenon (RP) attending 50 Italian centres for rheumatology and internal medicine. Systemic sclerosis was the most frequent condition associated with secondary RP, occurring in 216 (28.4%) patients. The other most frequent clinical diagnoses included systemic lupus erythematosus (52 cases: 6.8%) and rheumatoid arthritis (38 cases: 5%). Other RP-related diseases (hypertension, Sjogren's syndrome, mixed connective tissue disease, undifferentiated connective tissue disease, fibromyalgia, carpal tunnel syndrome, cryoglobulinemia, dermatopolymyositis, vasculitis, thoracic outlet syndrome, hypothyroidism, diabetes mellitus) occurred in less than 5% of cases. A total of 130 (48%) out of 268 patients with primary RP showed one or more clinical features indicating a fairly high risk of evolving into fully established systemic sclerosis. None of these patients fulfilled the ACR criteria for systemic sclerosis. This study shows that over 50% of patients with RP attending 50 Italian centres for rheumatology and internal medicine had a connective tissue disease. The large number of patients with primary RP and isolated clinical features of connective tissue disease indicates that more efforts should be focused on developing new criteria for the classification of RP. Publication Types: Multicenter study PMID: 9672994, UI: 98336865

Acta Psychiatr Scand 1998 Jun;97(6):450-7 Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome. Scott LV, Medbak S, Dinan TG Department of Psychological Medicine, St Bartholomew's and the Royal London School of Medicine, West Smithfield, UK. Hypofunctioning of the pituitary-adrenal axis has been suggested as the pathophysiological basis for chronic fatigue syndrome (CFS). Blunted adrenocorticotropin (ACTH) responses but normal cortisol responses to exogenous corticotropin-releasing hormone (CRH), the main regulator of this axis, have been previously demonstrated in CFS patients, some of whom had a comorbid psychiatric disorder. We wished to re-examine CRH activation of this axis in CFS patients free from concurrent psychiatric illness. A sample of 14 patients with CDC-diagnosed CFS were compared with 14 healthy volunteers. ACTH and cortisol responses were measured following the administration of 100 microg ovine CRH. Basal ACTH and cortisol values did not differ between the two groups. The release of ACTH was significantly attenuated in the CFS group (P < 0.005), as was the release of cortisol (P < 0.05). The blunted response of ACTH to exogenous CRH stimulation may be due to an abnormality in CRH levels with a resultant alteration in pituitary CRH receptor sensitivity, or it may reflect a dysregulation of vasopressin or other factors involved in HPA regulation. A diminished output of neurotrophic ACTH, causing a reduced adrenocortical secretory reserve, inadequately compensated for by adrenoceptor upregulation, may explain the reduced cortisol production demonstrated in this study. PMID: 9669518, UI: 98332181

Arthritis Care Res 1998 Apr;11(2):116-23 Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome. Finckh A, Morabia A, Deluze C, Vischer T Department of Internal Medicine, University of Geneva, Switzerland. OBJECTIVE: To compare the validity of self-reported questionnaires as response criteria of treatment efficacy in patients with fibromyalgia syndrome. METHOD: At the beginning of the treatment period, 70 fibromyalgia patients, randomly allocated to electro-acupuncture or placebo, underwent a clinical evaluation by rheumatologists and answered 1) a generic quality of life questionnaire--the Psychological General Well-Being Index (PGWB), 2) a specific function and symptom questionnaire, and 3) a pain questionnaire--the Regional Pain Score (RPS). The same evaluation was repeated at the end of the treatment period. Severity of the condition was assessed by a composite outcome score, a combination of different clinical outcome measures forming a clinical severity index. The variations between these questionnaire scores before and after treatment and the variations between the clinical severity indices estimated by clinicians were used as measures of the treatment impact. The first rationale for the validation was a positive correlation between clinical and questionnaire score changes. Another rationale for validation of the new instruments was the ability to identify the different treatment interventions. RESULTS: The correlation between the clinical severity index and the RPS was good (r = 0.62). Moreover, the RPS demonstrated a good discriminant power in detecting patients with effective treatment: it showed a specificity of 74% and a sensitivity of 75%. The PGWB correlated less well with the clinical score and was less discriminant. The specific function and symptom questionnaire showed little additional validity. CONCLUSIONS: Outcomes of syndrome severity such as pain and subjective well-being, as measured by self-reported questionnaires, can be valid instruments to evaluate treatment efficacy in short-term clinical trials. In the current study, the RPS proved to be particularly useful to assess the widespread tenderness of fibromyalgia and demonstrated high discriminative power. PMID: 9668734, UI: 98333331

Arthritis Care Res 1998 Apr;11(2):102-15 Sexual and physical abuse in women with fibromyalgia: association with outpatient health care utilization and pain medication usage. Alexander RW, Bradley LA, Alarcon GS, Triana-Alexander M, Aaron LA, Alberts KR, Martin MY, Stewart KE Department of Psychology (Medical Psychology Program), University of Alabama at Birmingham 35294, USA. OBJECTIVE: To evaluate the relationship between sexual and/or physical abuse and health care usage in patients with fibromyalgia (FM) and identify variables that may influence this relationship. METHODS: We assessed history of sexual/physical abuse, health care utilization, and medication usage, as well as related variables in 75 women with FM using standardized questionnaires, structured interviews, and laboratory pain perception tasks. RESULTS: Fifty-seven percent of FM patients reported a history of sexual/physical abuse. Compared to non-abused patients, abused patients reported significantly greater utilization of outpatient health care services for problems other than FM and greater use of medications for pain (P < or = 0.025). Consistent with our expectations, abused patients also were characterized by significantly greater pain, fatigue, functional disability, and stress, as well as by a tendency to label dolorimeter stimuli as painful regardless of their intensities (P < or = 0.05). Additional analyses suggested that the high frequency of sexual/physical abuse in our patients was associated primarily with seeking health care for chronic pain rather than the FM syndrome itself or genetic factors. CONCLUSION: There is an association in FM patients between sexual/physical abuse and increased use of outpatient health care services and medications for pain. This association may be influenced by clinical symptoms, functional disability, psychiatric disorders, stress, and abnormal pain perception. The relationships among these variables should be further tested in prospective, population-based studies. PMID: 9668733, UI: 98333330

Headache 1998 Jun;38(6):436-41 Migraine chronobiology. Fox AW, Davis RL Clinical Research and Regulatory Affairs, Cypros Pharmaceutical Corporation, Carlsbad, Calf, USA. This study was undertaken to determine whether migraine attacks exhibits circadian, menstrual, or seasonal variations in frequency and, thus, to characterize more precisely this relapsing, remittent, pleomorphic disease. An analysis of 3582 well-documented migraine attacks in 1698 adults was undertaken. The demographics of the study population accurately represented the known epidemiology of the disease. Migraine attacks started more frequently between 4 AM and 9 AM and within the first few days after onset of menses; this migraine periodicity is strongest amongst women not using oral contraceptives. Seasonal periodicity, if any, is clearly weaker than circadian or menstrual. These chronobiological features may assist in the differential diagnosis of migraine from premenstrual headache and fibromyalgia. PMID: 9664747, UI: 98329449

Clin Geriatr Med 1998 Aug;14(3):601-11 Soft tissue problems in older adults. Holland NW, Gonzalez EB Division of Rheumatology, Emory University School of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, Georgia 30033, USA. This article describes common soft tissue problems encountered in older adults, including fibromyalgia, selected bursitis/tendinitis syndromes, nerve entrapment syndromes, and miscellaneous topics such as Dupuytren's contractures, trigger fingers, palmar fasciitis, and reflex-sympathetic dystrophy. Clinical presentations, diagnosis, and treatment are emphasized. These are conditions that are frequently encountered but are generally diagnosed as arthritis or normal age-related problems. This article will hopefully enlighten the reader in distinguishing between these conditions. Publication Types: Review Review, tutorial PMID: 9664108, UI: 98330428

Am J Epidemiol 1998 Jul 1;148(1):72-7 Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome. Nisenbaum R, Reyes M, Mawle AC, Reeves WC Klemm Analysis Group, Atlanta, GA, USA. The objective of this study was to identify factors explaining the correlations among unexplained severe fatigue of different durations (1-5 months or > or =6 months) and symptoms reported as being significant health problems during a preceding 4-week period. Between June and December of 1994, a cross-sectional, random digit dialing telephone survey was conducted among residents of San Francisco, California. All subjects who reported having severe fatigue lasting for > or =1 month and a random sample of nonfatigued subjects were asked to participate in a detailed telephone interview. Data from 1,510 individuals aged 18-60 years who did not have medical or psychiatric conditions that could explain their severe fatigue were analyzed. Common factor analyses identified three correlated factors (defined as "fatigue-mood-cognition" symptoms, "flu-type" symptoms, and "visual impairment") that explained the correlations among fatigue lasting for > or =6 months and 14 interrelated symptoms. No factor explained the correlations among fatigue lasting for 1-5 months and other symptoms. The combination of fatigue of > or =6 months' duration and selected symptoms overlaps with published criteria used to define cases of chronic fatigue syndrome (CFS). Although symptoms described in this study were reported as appearing within the preceding month, and CFS symptoms must have been present for the previous 6 months, these results provide empirical support for the interrelations among unexplained fatigue of > or =6 months' duration and symptoms included in the CFS case definition. PMID: 9663406, UI: 98326539

Semin Arthritis Rheum 1998 Jun;27(6):348-59 A possible role for saliva as a diagnostic fluid in patients with chronic pain. Fischer HP, Eich W, Russell IJ Ruprecht-Karls-Universitat Heidelberg, Medizinische Klinik und Poliklinik, Germany. OBJECTIVES: The focus of this review was on proteins and peptides found in saliva. Of greatest interest were those neuropeptides relevant to nociception and to the pathogenesis of chronic pain syndromes. An additional goal was to develop a standardized protocol to collect saliva for laboratory assessment. METHODS: Data were obtained through discussion with experts at the medical schools in San Antonio and Heidelberg and a Medline literature search involving all relevant studies from 1966 to 1997. The literature search was based on the following key terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF). RESULTS: The mean concentration of SP in the saliva of healthy normal controls ranged from 9.6 to 220 pg/mL. Generally, the concentration of SP was approximately three times higher in saliva than in plasma. In a number of painful conditions, particularly tension headache, substantial elevations of salivary SP were found. Mean values for salivary CGRP in healthy controls were approximately 22 pmol/L and were significantly elevated in patients with migraine attacks or cluster headache. There were no data to indicate prior quantitative determination of NGF in human saliva. CONCLUSIONS: After sampling and processing techniques have been standardized, measurement of neuropeptides in human saliva could provide a valuable tool for study of patients with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and even fibromyalgia syndrome. Publication Types: Review Review, tutorial PMID: 9662753, UI: 98327255

J Orofac Pain 1998 Winter;12(1):35-41 Comparison of clinical and psychologic features of fibromyalgia and masticatory myofascial pain. Cimino R, Michelotti A, Stradi R, Farinaro C Department of Orthodontics, School of Dentistry, Faculty of Medicine, University of Naples, Federico II, Italy. The aim of this study was to investigate common symptoms and divergent features in fibromyalgia (FS) and masticatory myofascial pain (MFP) in patients affected by craniomandibular disorders. Twenty-three women with MFP and 23 women with FS were studied. All patients were examined by a dentist and by a rheumatologist. Craniomandibular disorders were assessed with a subjective symptoms questionnaire, detailed history interview, joint function examination, and manual palpation of masticatory and cervical muscles. The Middlesex Hospital Questionnaire was used to obtain personality profiles of the patients. The craniomandibular disorders questionnaire revealed various similarities in the two groups, the most striking of which were pain during mandibular function, articular noises, and headache. Both groups had muscle pain upon palpation; the mean scores (on a 0 to 4 scale) did not differ significantly between the two groups and ranged between 1.39 (SD 1.2) and 2.86 (SD 0.75). The mean value of active mouth opening was 40.9 mm (SD 9.1) in MFP patients and 44.6 mm (SD 7.2) in FS patients, while the mean value of passive opening was 49.6 mm (SD 6.0) in MFP patients and 49.8 mm (SD 3.5) in FS patients. These values did not differ significantly between the two groups, but did differ from the normal population, similar to the trend of the psychologic profile. The authors conclude that the physician should be alert to the need to conduct interdisciplinary evaluations in the diagnosis and management of FS and of MFP. PMID: 9656897, UI: 98321053

Br J Rheumatol 1998 May;37(5):491-5 Prevalence of the major rheumatic disorders in the adult population of north Pakistan. Farooqi A, Gibson T Department of Rheumatology and Physical Medicine, Pakistan Institute of Medical Sciences, Islamabad. The prevalence of rheumatic diseases in developing countries is largely unknown. Studies which allow comparison of data within the contrasting communities of the Third World and the developed world have the potential to provide insights into disease aetiologies. The current study compared the frequency of rheumatic symptoms (point prevalence) amongst 1997 adults distributed evenly between poor rural and poor urban communities and relatively affluent urban people. Comparisons were also made with similarly but previously derived prevalence rates of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and Pakistanis in England. A significantly higher prevalence of joint pain was seen in the north compared with the south. RA was more common in the north and similar to the frequency amongst Pakistanis resident in England. Ethnic and genetic susceptibility might have accounted for this. There was significantly more soft-tissue rheumatism and back pain in the northern rural population compared with those in the city. Fibromyalgia was almost completely absent from the urban affluent, but osteoarthritis of the knee was significantly more common in this community, perhaps due to relative obesity. RA was least in the urban poor, a phenomenon that might be attributable to earlier death of females or other undetermined factors. PMID: 9651074, UI: 98313094

Cas Lek Cesk 1998 May 18;137(10):295-8 [Chronic fatigue syndrome]. [Article in Czech] Litzman J, Lokaj J, Fucikova T Ustav klinicke imunologie a alergologie, FN u svate Anny, Brno, Praha. A great concern is recently given to the chronic fatigue syndrome in the Czech Republic. Unfortunately, published data allow us to state neither the etiologic agent nor the pathophysiology of the disease. Although many authors published various laboratory abnormalities, these changes are inconstant and do not allow to state a diagnosis of the chronic fatigue syndrome by a single laboratory test, and effective therapy is not known either. Psychotherapy, and in some cases antidepressants, are recommended by some authors to alleviate patient's symptoms. Neither immunological nor antiviral therapy showed positive results in controlled trials and are not generally used in most centers. Publication Types: Review Review, tutorial PMID: 9650359, UI: 98314045

Behav Res Ther 1998 May;36(5):527-35 Private body consciousness, anxiety and pain symptom reports of chronic pain patients. Ferguson RJ, Ahles TA Department of Psychiatry, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. robert.j.ferguson@dartmouth.edu An information processing model of pain symptom perception and reporting predicts that individuals prone to high levels of attentional self-focus and negative affect will report more pain than individuals low in these characteristics. Past research on college student and medical patient samples has shown that individuals high in private body consciousness (PBC), or attentional self-focus and who report higher levels of anxiety report more pain symptoms than counterparts low in PBC and anxiety. The present study examined effects of PBC and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain patients suffering chronic headache, low back pain, rheumatoid arthritis and fibromyalgia were included in the sample. A non-pain control sample (N = 31) was also studied to examine potential differences between controls and pain patients. Results indicated that pain patients reporting high levels of PBC reported more pain, although the effects of anxiety on pain reports among pain patients was not significant. Controls did not differ from pain patients on PBC, nor did the 4 groups of pain patients differ on PBC, suggesting PBC is a dispositional variable. Implications for the importance of attentional self-focus in pain symptom reporting are discussed. PMID: 9648328, UI: 98312134

Clin J Pain 1998 Jun;14(2):107-15 Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome: parental pain history and family environment. Schanberg LE, Keefe FJ, Lefebvre JC, Kredich DW, Gil KM Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. OBJECTIVE: The purpose of this study was to describe parental pain history and the family environment as it relates to the functional status of children with Juvenile Primary Fibromyalgia Syndrome (JPFS). DESIGN AND OUTCOME MEASURES: Twenty-nine parents of children with JPFS completed a pain history questionnaire, Von Korff Chronic Pain Grading system, and the Family Environment Scale (FES). Twenty-one adolescents with JPFS completed the FES, the Visual Analogue Scale for Pain, the modified Fibromyalgia Impact Questionnaire for Children, the Arthritis Impact Measurement Scales, and the Symptom Checklist-90-Revised. Correlational analyses were performed. RESULTS: Parents of children with JPFS reported multiple chronic pain conditions, including but not limited to fibromyalgia. Parental pain history and the family environment correlated with the health status of adolescents with JPFS. Children with JPFS perceived the family environment as significantly more cohesive than did their parents. Greater incongruence between parent and child responses on the FES positively correlated with greater impairment. CONCLUSIONS: These results suggest that family environment and parental pain history ay be related to how children cope with JPFS. Behavioral interventions targeting the family may improve the long-term functional status of children with JPFS. PMID: 9647451, UI: 98309666

Pathobiology 1998;66(2):53-8 Cellular sequences in stealth viruses. Martin WJ Center for Complex Infectious Diseases, Rosemead, Calif 91770, USA. Cloned DNA obtained from the culture of an African green monkey simian cytomegalovirus-derived stealth virus contains multiple discrete regions of significant sequence homology (p values ranging from 4 x 10(-3) to 1 x 10(-20)) to portions of known human cellular genes. The stealth virus was cultured from a patient with chronic fatigue syndrome (CFS). Earlier studies had revealed considerable sequence heterogeneity within DNA fragments isolated from virus-infected cells. A set of polymerase chain reaction (PCR) primers generated different PCR products when tested on stealth virus cultures from 4 patients with CFS. Several of the PCR products also contain regions of significant partial homology to distinct cellular sequences, including sequences repetitively expressed throughout the cellular genome. Stealth viruses may play an important role in the origins and in the genetic diversity of both viral and cellular sequences. PMID: 9645627, UI: 98307534

Clin Rheumatol 1998;17(2):89-94 A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids. Olin R, Klein R, Berg PA Department of Infectious Diseases, Huddinge Hospital, Karolska Institute, Stockholm, Sweden. The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p < 0.05) in feeling refreshed in the morning in the Ritanserin-treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved. Publication Types: Clinical trial Randomized controlled trial PMID: 9641502, UI: 98303204

Am J Med Sci 1998 Jun;315(6):405-12 Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia. Weigent DA, Bradley LA, Blalock JE, Alarcon GS Department of Medicine, The University of Alabama at Birmingham, 35294, USA. Fibromyalgia is a noninflammatory rheumatic disorder characterized by chronic widespread musculoskeletal pain. Although many studies have described the pain and other clinical symptoms associated with this disorder, the primary mechanisms underlying the etiology of fibromyalgia remain elusive. This article reviews recent data supporting the links among each of three systems--the musculoskeletal system, the neuroendocrine system, and the central nervous system (CNS), all of which appear to play major roles in fibromyalgia pathophysiology--and pain in fibromyalgia, and concludes by presenting a model of the pathophysiology of abnormal pain perception in fibromyalgia which integrates the research findings described. Publication Types: Review Review, tutorial PMID: 9638897, UI: 98300768

Am J Med Sci 1998 Jun;315(6):397-404 Advances in the treatment of fibromyalgia: current status and future directions. Alarcon GS, Bradley LA Division of Clinical Immunology and Rheumatology and the Multipurpose Arthritis and Musculoskeletal Diseases Center, The University of Alabama at Birmingham, 35294, USA. graciela.alacron@ccc.uab.edu Despite significant efforts devoted to understanding the etiopathogenesis of fibromyalgia, its treatment still presents a challenge to practicing clinicians, who must recognize the disorder and quantify the different symptoms in order to treat it. This article discusses recent research to identify sensitive and reliable measures for determining response to treatment among patients with FM, and the elements of therapeutic programs (pharmacologic and nonpharmacologic) for patients with FM along with the empirical or theoretical basis for their use. Future directions, including the need for systematic, controlled outcome studies of therapies and evaluation of variables which may mediate the effects of treatment, as well as demonstration that the effects produced in outcome studies generalize to settings beyond those in which the studies are initially conducted, are also discussed. Publication Types: Review Review, tutorial PMID: 9638896, UI: 98300767

Am J Med Sci 1998 Jun;315(6):385-96 Abnormal functional activity of the central nervous system in fibromyalgia syndrome. Mountz JM, Bradley LA, Alarcon GS Department of Radiology, The University of Alabama at Birmingham, 35233, USA. jmmountz@uab.edu The evaluation of pain is one of the major problems facing general practitioners and specialists in medicine. Although the source of pain can be usually be traced to specific abnormalities in a given organ system, some patients present with generalized pain syndromes, such as fibromyalgia, for which no specific source can be found. Some researchers have begun to consider that although there may be a somatic source of such pain at its initiation, over time the pain may be maintained or exacerbated by functional alterations in critical regions of the brain and spinal cord that are involved in pain processing or pain inhibition. This article describes the techniques currently used to measure regional cerebral blood flow (rCBF) in the brain by single photon emission computed tomography (SPECT) imaging, and reviews the SPECT and positron emission tomography literature concerning alterations in functional brain activity associated with pain in healthy individuals and in patients with chronic pain, including those with fibromyalgia. The article concludes by describing the implications of current knowledge about pain and abnormal functional brain activity in the understanding of the pathophysiology of fibromyalgia and in the development of therapeutic strategies to manage patients with this disorder. Publication Types: Review Review, tutorial PMID: 9638895, UI: 98300766

Am J Med Sci 1998 Jun;315(6):377-84 Advances in fibromyalgia: possible role for central neurochemicals. Russell IJ Department of Medicine, The University of Texas Health Science Center, San Antonio 78284-7868, USA. The neurophysiologic term allodynia has been applied to fibromyalgia because people with that disorder experience pain from pressure stimuli which are not normally painful. The nociceptive neurotransmitters of animal studies are now relevant to this human model of chronic, widespread pain. Evidence is presented to implicate several chemical pain mediators (including serotonin, substance P, nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This perception is hopeful because it offers many new options for the development of innovative therapy. Publication Types: Review Review, tutorial PMID: 9638894, UI: 98300765

Am J Med Sci 1998 Jun;315(6):367-76 Sleep in fibromyalgia patients: subjective and objective findings. Harding SM Sleep/Wake Disorders Center, University of Alabama at Birmingham, 35294, USA. harding@pulm.dom.uab.edu Fibromyalgia (FM) patients report early morning awakenings, awakening feeling tired or unrefreshed, insomnia, as well as mood and cognitive disturbances; they may also experience primary sleep disorders including sleep apnea. Longitudinal studies have demonstrated the chronic nature of these disturbances in patients with FM. A distinct relationship exists between poor sleep quality and pain intensity. Polysomnographic findings during sleep in these patients include an alpha frequency rhythm, termed alpha-delta sleep anomaly, which is also seen in normal controls during stage 4 sleep deprivation; deep pain induced during sleep in normal controls also causes this anomaly. Sleep architecture is altered in FM patients showing an increase in stage 1, a reduction in delta sleep, and an increased number of arousals. Before prescribing pharmacologic compounds aimed at modifying sleep, adequate pain control and sleep habits should be achieved; tricyclic antidepressants, trazadone, zopiclone, and selective serotonin reuptake inhibitors, however, may be required. More research is needed to elucidate the cellular and molecular mechanisms involved in the sleep disturbances occurring in patients with FM. Publication Types: Review Review, tutorial PMID: 9638893, UI: 98300764

Am J Med Sci 1998 Jun;315(6):359-66 Neuroendocrine abnormalities in fibromyalgia and related disorders. Crofford LJ Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0680, USA. Fibromyalgia (FM) and related syndromes are poorly understood disorders that share symptoms such as pain, fatigue, sleep disturbances, and psychological distress. These syndromes are more common in women, and they are associated with psychological or physical stressors. The neuroendocrine axes are essential physiologic systems that allow for communication between the brain and the body. Interconnections among the neuroendocrine axes lead to coordinate regulation of these systems in both a positive and negative fashion. Several neuroendocrine axes have been shown to be dysfunctional in patients with FM. Although we do not yet understand the relationship between the reported disturbances of neuroendocrine function and the development or maintenance of FM and related syndromes, the authors have proposed that these abnormalities are important in symptomatic manifestations. This article reviews data showing disturbances of the neuroendocrine axes in FM and proposes a hypothesis of the development and maintenance of FM related to neuroendocrine disturbances. Publication Types: Review Review, tutorial PMID: 9638892, UI: 98300763

Am J Med Sci 1998 Jun;315(6):351-8 Skeletal muscle abnormalities in patients with fibromyalgia. Olsen NJ, Park JH Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. nancy.olsen@mcmail.vanderbilt.edu Widespread muscle pain and tender points are the most common complaints of fibromyalgia patients, and the underlying mechanisms responsible for these symptoms have been studied intensively during the past decade. It has been suggested that fatigue and pain may lead to decreased levels of physical activity in many patients. The resulting deconditioned state may itself contribute to muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety, depression, or irritable bowel also may have a negative impact on muscle function and level of daily activities. The important interactions between the central nervous and musculoskeletal systems may involve another element, the neuroendocrine stress-response system. This review will consider both the current state of knowledge and also future studies which might be designed to answer more effectively the outstanding questions regarding the underlying pathogenesis of fibromyalgia. Publication Types: Review Review, tutorial PMID: 9638891, UI: 98300762

Am J Med Sci 1998 Jun;315(6):346-50 Fibromyalgia is not a muscle disorder. Simms RW Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA. rsimms@med-med1.bu.edu Originally described as "fibrositis," fibromyalgia has long been considered a muscle disorder, and many studies have investigated the possible pathologic basis of the disorder by examining muscle tissue, using various methodologic approaches. Although initial studies suggested a possible pathologic basis in muscle, most had serious methodologic limitations. More recent studies, however, have avoided methodologic pitfalls and indicate that the muscles of patients with fibromyalgia are normal. When data from studies of tenderness are also taken into account, the weight of evidence suggests that fibromyalgia is a chronic pain syndrome which has a central rather than peripheral or muscular basis. Publication Types: Review Review, tutorial PMID: 9638890, UI: 98300761

Med Confl Surviv 1998 Apr-Jun;14(2):156-65 Gulf War illnesses: complex medical, scientific and political paradox. Nicolson GL, Nicolson NL Institute for Molecular Medicine, Huntington Beach, CA 92649-1041, USA. gnicimm@ix.netcom.com Gulf War illnesses are a collection of disorders that for the most part can be diagnosed and treated, if effective programmes exist to assist veterans, and in some cases their immediate family members. Although these illnesses are complex and have multi-organ signs and symptoms, a proportion of these patients can be identified as having Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and/or Fibromyalgia Syndrome (FMS). Although there are many possible causes of CSF/ME/FMS, chronic infections can explain, at least in a subset of patients, the apparent transmission of these illnesses to family members and the appearance of chronic, multi-organ and auto-immune signs and symptoms. Unfortunately, many veterans who have been diagnosed with chronic infections, such as mycoplasmal infections, cannot obtain adequate treatment for their condition, resulting in their reliance on private physicians and clinics for assistance. This lack of response may ultimately be responsible for the transmission of the illness to non-veterans. PMID: 9633269, UI: 98296925

J Rheumatol 1998 Jun;25(6):1180-6 The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I. Older SA, Battafarano DF, Danning CL, Ward JA, Grady EP, Derman S, Russell IJ Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6272, USA. OBJECTIVE: To assess the effects of delta wave sleep interruption (DWSI) on pain thresholds and fibromyalgia-like symptoms. To examine the potential correlations between DWSI and serum insulin-like growth factor 1 (IGF-1). METHODS: Thirteen healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain thresholds were measured by dolorimetry and symptoms by visual analog scale. Six subjects not undergoing DWSI served as dolorimetry and symptom controls (Group 2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and after DWSI. RESULTS: No significant differences in pain thresholds as a function of condition (baseline, DWSI, recovery) or overnight change were detected between or within groups (p>0.05). Morning mean dolorimeter scores were lower than evening scores in both groups during all 3 conditions, and were lower in Group 1 than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum levels of IGF-1 from Group 1 subjects showed no significant change after DWSI (p>0.05). CONCLUSION: In our study subjects, 3 nights of DWSI caused no significant lowering of pain thresholds compared with a control group. Subjects appeared to have lower pain thresholds in the mornings, and DWSI appeared to augment this effect. Symptoms were more apparent during DWSI, but were primarily related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather than acute DWSI, or may be dependent on factors other than disturbances of delta wave sleep. PMID: 9632083, UI: 98293844

Clin Exp Rheumatol 1998 May-Jun;16(3):305-8 Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4 cases. Cantini F, Salvarani C, Olivieri I, Niccoli L, Padula A, Bellandi F, Palchetti R Unita Reumatologica, II Divisione di Medicina Interna, Ospedale di Prato, Italy. Patients are said to have inflammatory spinal pain if they fulfill at presentation 4 of the following 5 criteria: duration of spinal discomfort for at least 3 months, spinal morning stiffness, age less than 40, insidious onset of symptoms, and no relief from pain with rest, but improvement with exercise. Inflammatory spinal pain is typical of the spondylarthropathies. Only in a minority of the cases it is found in other rheumatic disorders such as rheumatoid arthritis, fibromyalgia or infectious spondyilitis. Tuberculous spondylitis is rarely mentioned as a possible cause of inflammatory spinal pain. We describe 4 patients with tuberculous spondylitis seen over a 3-year period who met the clinical criteria for inflammatory spinal pain at presentation. We conclude that inflammatory spinal pain may be a presenting feature, albeit rare, of tuberculous spondylitis. Awareness of this finding should help facilitate the proper diagnosis and the institution of appropriate therapy. PMID: 9631755, UI: 98295250

Neuromuscul Disord 1998 May;8(3-4):204-9 Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R Division of Clinical Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, UK. r.lane@cxwms.ac.uk It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers. There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation. These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue. PMID: 9631403, UI: 98294864

Altern Med Rev 1998 Jun;3(3):187-98 The detoxification enzyme systems. Liska DJ HealthComm International, Inc. P.O. Box 1729, Gig Harbor, WA 98335, USA. deann@healthcomm.com The human body is exposed to a wide array of xenobiotics in ones lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning. Publication Types: Review Review, tutorial PMID: 9630736, UI: 98331853

Ann N Y Acad Sci 1998 May 1;840:684-97 Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Demitrack MA, Crofford LJ Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms. Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia). How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function. In order to provide a more refined view of the nature of the HPA dusturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition. Publication Types: Review Review, tutorial PMID: 9629295, UI: 98292940

Z Rheumatol 1998 Apr;57(2):89-94 [Interdisciplinary group therapy for fibromyalgia]. [Article in German] Strobel ES, Wild J, Muller W Park-Klinik Bad Kissingen. Fibromyalgia is present in 2% of the general population and leads to impairment by chronic pain and fatigue. It does not improve without therapy directed at the symptoms of fibromyalgia. We describe our interdisciplinary group treatment for patients with fibromyalgia. They received a physical examination, ergometry and psychometric tests both at admission and before discharge, and they were questioned to the degree and localization of their pain, to fatigue, sleeping disorders and functional symptoms. Therapy included information about fibromyalgia, learning of coping strategies, relaxation and endurance training. Our results show that our interdisciplinary group treatment is effective for fibromyalgia and improves anxiety, depression and well being after a period of 5 weeks of in-patient rehabilitation. PMID: 9627947, UI: 98291417

Psychiatry Clin Neurosci 1998 Apr;52(2):234-235; Clinical characteristics of circadian rhythm sleep disorders. Kamei Y, Urata J, Uchiyaya M, Hayakawa T, Ozaki S, Shibui K, Okawa M; Department of Psychiatry, Kohnodai Hospital, National Center of Neurology and Psychiatry, Chiba, Japan.

From our practice at the sleep disorders clinic in Kohnodai Hospital, National Center of Neurology and Psychiatry (NCNP), we report the clinical characteristics of circadian sleep-wake rhythm disorders. Nearly 90% of circadian rhythm sleep disorders were diagnosed as delayed sleep phase syndrome (DSPS) or as non-24 sleep-wake syndrome (non-24). While DSPS was equally common in males and females, non-24 was more frequently seen in men. It was of psychiatric interest that a considerable number of patients had depressive states in the course of their circadian rhythm sleep disorders. Difficulty in adapting to social life was more severe in patients with non-24 than in those with DSPS.

Holist Nurs Pract 1998 Apr;12(3):55-63; Fibromyalgia and chronic fatigue: the holistic perspective. Kenner C; Department of Parent-Child Health Nursing, College of Nursing and Health University of Cincinnati, Ohio, USA.

Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are not new conditions, but they are receiving more attention as more research is conducted. These two conditions are primarily women's health problems. In some instances, there may be a genetic predisposition for these conditions. The impact of FMS and CFS can be devastating both physically and emotionally. The treatment plan must be interdisciplinary and holistic and include alternative therapies if the client and family are to be truly supported and helped in coping with these chronic conditions.

Br J Rheumatol 1998 Apr;37(4):382-386; The association of soft-tissue rheumatism and hypermobility. Hudson N, Fitzcharles MA, Cohen M, Starr MR, Esdaile JM; Rheumatic Disease Unit, McGill University, Montreal, Quebec, Canada.

Soft-tissue rheumatism (STR--tendinitis, bursitis, fasciitis and fibromyalgia) accounts for up to 25% of referrals to rheumatologists. The estimated prevalence of generalized hypermobility in the adult population is 5-15%. There have previously been suggestions that hypermobile individuals may be predisposed to soft-tissue trauma and subsequent musculoskeletal pain. This study was designed to examine the mobility status and physical activity level in consecutive rheumatology clinic attendees with a primary diagnosis of STR. Of 82 patients up to age 70 yr with STR, 29 (35%) met criteria for generalized hypermobility. Hypermobile compared to non-hypermobile individuals reported significantly more previous episodes of STR (90% vs 51%, P < 0.01), and more recurrent episodes of STR at a single site (69% vs 38, P < 0.001). Although we were unable to show any difference in the time spent carrying out physical activity between the two groups, the hypermobile patients were performing significantly more repetitive activities. When specific anatomical sites of STR were analysed, small joints (elbows, hands and feet) currently affected with STR were more likely to show localized hypermobility than if those joints were asymptomatic. These findings suggest that hypermobility may be a factor in the development of STR. Repetitive activity may be a contributing factor towards STR in some hypermobile individuals.

Br J Med Psychol 1998 Jun;71( Pt 2):185-194; The role of anxiety and depression in fatigue and patterns of pain among subgroups of fibromyalgia patients. Kurtze N, Gundersen KT, Svebak S; North-Troendelag Research Institute, Steinkjer, Norway.

This study explored the relationship of anxiety and depression with two major symptoms of fibromyalgia, pain and fatigue, among fibromyalgia patients (N = 322). Due to collinearity between anxiety and depression scores, extreme groups were defined according to high versus low anxiety and depression scores. Two-thirds of the initial sample were excluded by this approach, which permitted a two by two factorial split-plot ANOVA for the assessment of main effects and the interaction of anxiety and depression upon pain and fatigue. Results stated independent, additive, effects of anxiety and depression upon levels of pain and fatigue, whereas interaction between anxiety and depression failed to significantly explain symptom differences among the participants. Correlational analyses indicated widespread pain among the low anxiety subgroups. In contrast, widespread pain was not indicated among anxious patients with low scores on depression. The findings support the hypothesis that (1) anxiety and depression are independently associated with severity of pain symptoms in fibromyalgia, and that (2) patients with high anxiety and low depression may communicate to the medical doctor in ways that involve a risk of diagnosing fibromyalgia when the criterion of widespread pain is not supported. These conclusions were confirmed by results from ANCOVAs that permitted more extensive control of collinearity among variables.

Zh Nevrol Psikhiatr Im S S Korsakova 1998;98(4):40-43; [Treatment of fibromyalgia]. Tabeeva GR, Levin IaI, Korotkova SB, Khanunov IG

The paper reports the results of therapy of 23 patients with fibromyalgia (FM). Tetracyclic antidepressant lerivon, was administered to group 1, nonsteroid antiinflammatory (NSAI) preparation nurofen to group 2 and phototherapy (exposure to bright white light) was used in group 3. Clinical effect in the form of a decrease of both the intensivity of algesic syndrome and autonomic manifestations as well as improvement of night sleep were clearly seen in group 1. Manifestations of both anxious and depressive disorders were less pronounced. Treatment by Nurofen resulted in slight decrease of intensivity of pains but didn't lead to pronounced alterations of emotional sphere. Administration of either Lerivon or Nurofen promoted the increase of pain thresholds (according to the data of nociceptive flexory reflex). The data obtained testified the necessity of complex therapy of FM patients including administration of antidepressants and analgetic drugs of NSAI group. Dynamic polysomnographic examination of patients from group 3 revealed the increase of total sleep duration, decrease of the time of falling asleep, the latent period of the phase of the fast sleep, activated movement index, intensivity of movements and the time of being awake in the sleep. The conclusion was made that it was worth while to use phototherapy as alternative, nonmedicine method of phothotherapy.

Int J Clin Pharmacol Res 1998;18(1):13-19; Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo. Biasi G, Manca S, Manganelli S, Marcolongo R; Institute of Rheumatology, University of Siena, Polyclinic Le Scotte, Italy.

This study assessed the analgesic action of tramadol compared with placebo in patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one male) were treated according to a double-blind crossover experimental design. Each patient, after signing informed consent, was randomly allocated to either tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo for a single dose treatment. At the second visit, patients crossed over to the other drug for a further single dose treatment. There was a wash-out period of 1 week. Nine patients completed the study, while in three cases (two tramadol, one placebo) the study was discontinued due to the onset of side effects. The assessment of efficacy, carried out at the baseline and 15 min and 2 hours after administration of each dose, involved the use of a visual analog scale (VAS 100 mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic" tender points and nine "control" tender points for fibromyalgic pain. During the first treatment cycle effective control of spontaneous pain was achieved with tramadol, which determined a reduction of 20.6% while with the placebo spontaneous pain increased by 19.8%. With pressure dolorimetry there were no clinically important differences observed after either active treatment or placebo. The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.

Schweiz Rundsch Med Prax 1998 Apr 15;87(16):538-545; [No title available]. Kissel W, Mahnig P; MEDAS Zentralschweiz, Luzern.

MEDAS-agencies are medical institutions within the Swiss Disability Insurance, which specialize in assessing the working capacity of candidates who apply for a disability pension. Degenerative and other chronic pain disorders of the musculoskeletal system form the majority of cases that we investigate. Fibromyalgia is one of our most frequent diagnoses (8.6%). We become involved in cases on average 8.5 years after the first onset of painful symptoms and on average 2.5 years after the patients have ceased to work. Our experience, tells us that fibromyalgia is usually associated with psychological disturbances; thus our psychiatrists have found important psychological problems in 86.7% of applicants. They found mainly neurotic and depressive syndromes. Our investigations have shown that psychological disturbances precede the onset of musculoskeletal pain in about 70% of patients. Therefore, we don't consider fibromyalgia syndrome as an entity of its own, but regard it as a pain syndrome in which there are underlying psychological problems in most cases.

Cleve Clin J Med 1998 May;65(5):261-266; The connection between chronic fatigue syndrome and neurally mediated hypotension. Wilke WS, Fouad-Tarazi FM, Cash JM, Calabrese LH; Department of Rheumatic and Immunologic Disease, Cleveland Clinic Foundation, OH 44195, USA.

Research from several groups of investigators indicates that some patients with chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to upright posture. If confirmed, these findings may explain some of the symptoms of chronic fatigue syndrome. There is also speculation that neurally mediated hypotension may be present in fibromyalgia. This article discusses the original research in this area, the results of follow-up studies, and the current approach to treating patients with chronic fatigue syndrome in whom neurally mediated hypotension is suspected.

J Rheumatol 1998 May;25(5):892-895; Fatigue in lupus is not correlated with disease activity. Wang B, Gladman DD, Urowitz MB; University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Disease, The Toronto Hospital, Ontario, Canada.

OBJECTIVE: The relationship between fatigue and disease activity in systemic lupus erythematosus (SLE) has been questioned. We examined whether self-reported fatigue in patients with SLE is correlated with disease activity. METHODS: Consecutive patients with SLE at the University of Toronto Lupus Clinic were evaluated for disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They were also evaluated for fibromyalgia (FM) by American College of Rheumatology criteria. One hundred patients completed the following health status questionnaires: the Fatigue Severity Score (FSS), Center for Epidemiologic Studies Depression Scale (CES-D), and Medical Outcomes Study Short Form Health Survey (SF-20). Disease activity was measured by the SLEDAI. Statistical correlations were made using the Spearman test. RESULTS: No significant correlation was found between FSS scores and SLEDAI (p = NS). Fatigue was found to be highly correlated with the presence of FM (p < 0.05) and depression (p < 0.01). In addition, fatigue was significantly associated with lower performance in all 6 domains of the SF-20 (p < 0.001); disease activity correlated with decreases in social function, mental health, and health perception areas of the SF-20. SLEDAI was not found to correlate with FM (p = NS). CONCLUSION: Fatigue in patients with SLE does not correlate with disease activity. However, fatigue is correlated with FM, depression, and lower overall health status in this population. Fatigue is a manifestation of these conditions, which are commonly co-expressed in SLE, and may reflect a decreased overall coping ability in these patients, rather than active disease itself.

J Rheumatol 1998 May;25(5):852-858; Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada. Bellamy N, Kaloni S, Pope J, Coulter K, Campbell J; Department of Medicine, University of Western Ontario, London, Canada.

OBJECTIVE: To assess the extent to which quantitative clinical measurement is performed by rheumatologists in the longitudinal followup of patients with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and fibromyalgia (FM) in routine outpatient practice in Canada. METHODS: A cross sectional postal survey was conducted using an 18 item self-administered questionnaire sent to Canadian Rheumatology Association members. RESULTS: Rheumatologists (response rate 85%) were more likely to longitudinally follow patients with RA and AS than those with OA or FM. There was a high degree of variability in the methods used to monitor patients longitudinally. Many measures used in clinical research were used infrequently in routine clinical practice. In general, the major health status measures surveyed were not used in clinical monitoring. There was a high level of agreement (>80%) that the characteristics required of an outcome measure for use in clinical practice should include simplicity, brevity, ease of scoring, reliability, validity, and sensitivity to change. CONCLUSION: The majority of Canadian rheumatologists perform outcome measurement during the longitudinal followup of their outpatients with RA, AS, OA, and FM. However, the process lacks standardization. High performance health status measures, developed for clinical research, have not been widely adopted in rheumatology practices. There is agreement on the characteristics required by Canadian rheumatologists for measurement procedures used in routine clinical care. Quantitative measurement in clinical practice using standardized procedures is an attainable, but as yet, unrealized opportunity.

J Neurol Sci 1998 Jan 21;154(1):18-25; Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome patients. Saggini R, Pizzigallo E, Vecchiet J, Macellari V, Giacomozzi C; Institute of Medical Pathophysiology, University G. D'Annunzio, Chieti, Italy.

Chronic Fatigue Syndrome (CFS) has been widely studied and a lot of information is available in the literature regarding the immunological, virological, neuroendocrinal and psychiatric aspects of the disease, but its aetiology is still poorly understood. Great attention has also been paid to the alteration of the muscular function caused by CFS. The aim of the present work was to study CFS patients' gait in order to find out objective measures which can better characterize the pathology. Spatial and temporal parameters of gait were collected from a group of 12 CFS informed volunteers by using the typical instrumentation of movement analysis, and raw data were statistically elaborated. Comparisons with reference data from a population of healthy subjects revealed significant abnormalities in the symmetry indices of the bilateral parameters and in the linear relationships among parameters, and between these parameters and the physical characteristics of the patients. Interestingly, the abnormalities were present as from the beginning of the gait, which indicates that they are unlikely to be caused by the rapid increasing fatigue. This strengthens the hypothesis of a direct involvement of the central nervous system (CNS) in the onset of the disease.

Integr Physiol Behav Sci 1998 Jan;33(1):61-71; The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Dykman KD, Tone C, Ford C, Dykman RA; Mannatech Inc., Coppell Texas 75019, USA.

This article reports the results of a within-subject design. Fifty subjects with a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed using a structured interview from. Each subject was interviewed initially, and again nine months later (follow-up). Subjects had, on their own, consumed nutritional supplements including freeze-dried aloe vera gel extract; a combination of freeze-dried aloe vera gel extract and additional plant-derived saccharides; freeze-dried fruits and vegetables in combination with the saccharides; and a formulation of dioscorea complex containing the saccharides and a vitamin/mineral complex. With medical treatments, approximately 25 percent of FM patients improve, but t