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ME Research UK — Database of Research Publications 1997

Authors Author Address Title Publication Abstract

Albus C.

Institut und Poliklinik fur

Psychosomatik und

Psychotherapie, Universitat

zu Koln.

[Chronic fatigue syndrome--a

disease entity or an

unspecified psychosomatic

disorder][article in German]

Z Arztl Fortbild Qualitatssich

1997 Dec;91(8):717-21

In spite of its nature as an often severe and disabeling disease, it is still unclear, whether the Chronic

Fatigue Syndrome (CFS) is an entire disease of its own right or not. Moreover, there is a growing evidence

that patients with CFS belong to an inhomogeneous group with different etiologic constellations. Specific

somatic factors, e.g. viruses, seem to be less important for onset than certain personality-traits like

depressiveness and workaholism. These traits lead to an increased vulnerability to unspecific psychological

or biological stressors that may cause chronic fatigue by complex psychosomatic interferences. Concerning

diagnosis, there are no specific methods or results available, the same is true for pharmacological treatment.

As a consequence, practitioners should be aware not to miss a somatic disease causing fatigue, and, parallel

to this, start right from the beginning talking about the psychosomatic background of CFS. Furthermore,

psychotherapy has shown to be effective in CFS.

Allain TJ, Bearn JA,

Coskeran P, Jones J,

Checkley A, Butler J,

Wessely S, Miell JP.

Anderson JS, Ferrans CE.

Ax S, Gregg VH, Jones D.

Baschetti R.

Baschetti R.

Baschetti R.

Department of Medicine,

Kings College School of

Medicine and Dentistry,

London, United Kingdom.

University of Illinois at

Chicago Medical Center,

Department of Psychiatry

60612, USA.

Birkback College, University

of London, England.

Changes in growth hormone,

insulin, insulinlike growth

factors (IGFs), and IGFbinding

protein-1 in chronic

fatigue syndrome.

The quality of life of persons

with chronic fatigue

syndrome.

Chronic fatigue syndrome:

sufferers' evaluation of

medical support.

Etiology of chronic fatigue

syndrome.

Lung function test findings in

patients with chronic fatigue

syndrome (CFS)

Similarity of symptoms in

chronic fatigue syndrome and

Addison's disease.

Biol Psychiatry 1997 Mar

1;41(5):567-73

J Nerv Ment Dis 1997

Jun;185(6):359-67

J R Soc Med 1997

May;90(5):250-4

Am J Med 1997

Apr;102(4):422-3 Comment

on: Am J Med. 1996

May;100(5):548-54

Aust N Z J Med 1997

Jun;27(3):346 Comment on:

Aust N Z J Med. 1996

Aug;26(4):563-4

Eur J Clin Invest 1997

Dec;27(12):1061-2 Comment

on: Eur J Clin Invest. 1997

Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin.

Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was

to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth

factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia.

We compared levels of GH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), insulin, and C-peptide in

nondepressed CFS patients and normal controls. We found attenuated basal levels of IGF-I (214 +/- 17 vs.

263.4 +/- 13.4 micrograms/L, p = .036) and IGF-II (420 +/- 19.8 vs. 536 +/- 24.3 micrograms/L, p = .02) in

CFS patients and a reduced GH response to hypoglycemia (peak GH; 41.9 +/- 11.5 vs. 106.0 +/- 25.6

mU/L, p = .017). Insulin levels were higher (7.6 +/- 1.0 vs. 4.3 +/- 0.8 mU/L, p = .02) and IGFBP-1 levels

were lower (19.7 +/- 4.6 vs. 43.2 +/- 2.7 mg/L, p = .004) in CFS patients compared with controls. This

study provides preliminary data abnormalities of the GH-IGF axis in CFS. It is not apparent whether these

changes are components of a primary pathological process or are acquired secondary to behavioral aspects

of CFS such as reduced physical activity.

This descriptive study used a between-methods triangulation design to analyze the multiple dimensions of

quality of life in persons with chronic fatigue syndrome (CFS). This method, which refers to the

combination of both quantitative and qualitative methods in the same study, allowed the authors to obtain

more comprehensive and robust data than could be obtained by either method alone. A convenience sample

of 110 persons with CFS completed the quality of life index and CFS questionnaire, and a subset of 22

persons were interviewed regarding their lived experience with CFS. Overall scores on the quality of life

index were significantly lower in CFS than for other chronic illness groups. Subjects reported the lowest

quality of life scores in health and functioning domain. Indepth interviews provided a more complete

understanding of the quality of life in CFS and further explained the low ratings that were found on the

quality of life index. The findings suggest that quality of life is particularly and uniquely disrupted in CFS.

In response to reports of negative cooperation between sufferers of chronic fatigue syndrome (CFS) and

their doctors, semi-structured interviews were conducted with sufferers from two different patient samples.

Satisfaction with support received and with medical professionals in general was low. Sufferers complained

about insufficient informational as well as emotional support from their doctors, and as a consequence most

opted for alternative or complementary forms of treatment. In addition, disagreements over illness aetiology

and treatment precluded effective cooperation. If satisfaction and compliance are to improve, sufferers will

need more information about CFS and more support.


ME Research UK — Database of Research Publications 1997

Apr;27(4):257-67

Baschetti R. Chronic fatigue syndrome. QJM 1997 Nov;90(11):723

Comment on: QJM. 1997

Mar;90(3):223-33

Bazelmans E, Vercoulen

JH, Galama JM, van Weel

C, van der Meer JW,

Bleijenberg G.

Beh HC.

Bell DS

Bell IR, Michele E. Walsh,

Anita Gross, Jane

Gersmeyer, Gary E.

Schwartz, Philip Kanof

Bennett A.

Afd. Medische Psychologie,

Academisch Ziekenhuis,

Nijmegen.

Department of Psychology,

University of Sydney, New

South Wales, Australia.

[Prevalence of chronic

fatigue syndrome and

primary fibromyalgia

syndrome in The

Netherlands].[article in

Dutch] Erratum in: Ned

Tijdschr Geneeskd 1997 Sep

13;141(37):2686

Effect of noise stress on

chronic fatigue syndrome

patients.

Illness Onset Characteristics

in Children with Chronic

Fatigue Syndrome and

Idiopathic Chronic Fatigue

Cognitive Dysfunction and

Disability in Geriatric

Veterans with Self-Reported

Intolerance to Environmental

Chemicals

A view of the violence

contained in chronic fatigue

syndrome.

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1520-3

J Nerv Ment Dis 1997

Jan;185(1):55-8

Journal of Chronic Fatigue

Syndrome 1997: 3(2): 43 - 51

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 15 - 42

J Anal Psychol 1997

Apr;42(2):237-51

OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) and of primary fibromyalgia

syndrome (PFS) in the Netherlands. DESIGN: Questionnaire. SETTING: Department of Medical

Psychology, University Hospital Nijmegen, the Netherlands. METHOD: A questionnaire was mailed to all

the 6657 general practitioners in the Netherlands in order to inform them of the existence of CFS and to ask

them if they had any CFS or PFS patients in their practices. RESULTS: Sixty percent (n = 4027) of the

general practitioners returned the questionnaire. Of all the general practitioners, 27% said they had no CFS

patients, 23% said they had 1 CFS patient, while 21% had 2 CFS patients, and 29% said they had 3 or more

CFS patients in their practice. Concerning PFS the results were 17% (no PFS patients), 18%, 18% and

47%, respectively. With a mean practice of 2486 patients per general practice, the estimated prevalence of

CFS was 112 per 100,000 and that of PFS 157 per 100,000 persons. Of the CFS patients 81% were women

and 55% were 25-44 years old; for PFS these figures were 87% and 48% respectively. CONCLUSION:

Extrapolation of the study results indicates that there are at least 17,000 CFS patients and 24,000 PFS

patients in the Netherlands. The found prevalence is probably an under-estimation.

Twenty-three children and adolescents with unexplained chronic fatigue were evaluated with emphasis

upon illness-onset characteristics. Ten subjects had an acute, "flu-like" onset, and four of these subjects had

episodes of mild fatigue in the year prior to onset. The thirteen remaining subjects had a gradual onset of

chronic fatigue, the majority describing increasing episodes of apparent infectious illnesses associated with

fatigue. In these subjects, the fatigue eventually became constant, causing reduction in overall activity

levels. In a comparison of subjects who did and did not meet diagnostic criteria for chronic fatigue

syndrome, there were no differences in onset characteristics, but differences were noted in illness severity.

The majority of children and adolescents with unexplained chronic fatigue had a gradual onset of

debilitating symptoms

The symptom of sensitivity or intolerance to low levels of environmental chemicals (CI) is a characteristic

of several clinical conditions, such as multiple chemical sensitivity (MCS), chronic fatigue syndrome

(CFS), fibromyalgia (FM), and the "Persian Gulf Syndrome." Lesser degrees of CI also occur in 15-30% of

non-clinical populations. The present study examined the prevalence and concomitant health patterns of CI

in elderly veterans in a VA primary care medical clinic (N = 160, primarily men). Thirty-seven percent of

the sample endorsed the screening question asking whether or not they considered themselves "especially

sensitive to certain chemicals." The group with CI reported a significantly higher rate of physical disability

and increased susceptibility to becoming sick. The CI group reported significantly decreased rates of

current cigarette smoking and alcohol use. Those with and those without CI did not differ in level of

depression or in past occupational chemical exposures. However, the CI group scored significantly lower on

a screening test for cognitive dysfunction, including a verbal memory performance pattern consistent with

early dementia. When the groups were subdivided into individuals high and low in depression, the

depressives without CI reported the highest rate of prior occupational exposure to pesticides. The subgroup

who had both CI and depression performed most poorly on the attention/concentration screening test.

Taken together, the data suggest that CI as a symptom is extremely common in older male veterans and may

be a marker for increased risk of further cognitive decline and/or loss of functional independence. However,

the role of occupational chemical exposures in initiating CI in these non-MCS patients is unclear and

requires additional study.

In this paper I ask whether there might be any one particular psychopathology likely to be linked

specifically with the physical illness known as chronic fatigue syndrome (CFS) or myalgic

encephalomyelitis (ME), and whether CFS/ME aids and abets and "fits' an original mental state. I think the

question cannot yet be answered. However it is my hypothesis that in some personality structures the onset

of CFS/ ME following a physical illness exacerbates negativity and is an aspect of ordinary depression


ME Research UK — Database of Research Publications 1997

Bennett AL, Chao CC, Hu

S, Buchwald D, Fagioli LR,

Schur PH, Peterson PK,

Komaroff AL.

Bennett AL, Mayes DM,

Fagioli LR, Guerriero R,

Komaroff AL.

Berlin B.

Bertolin JM, Calvo J.

Bleijenberg G.

Bowman MA, Kirk JK,

Michielutte R, Preisser JS.

Controlled Clinical Trial

Chronic Fatigue Syndrome

Cooperative Research Center,

Brigham and Women's

Hospital, Boston,

Massachusetts, USA.

Department of Medicine,

Brigham and Women's

Hospital, Boston, MA 02115,

USA.

Academisch Ziekenhuis, afd.

Medische Psychologie,

Nijmegen.

Elevation of bioactive

transforming growth factorbeta

in serum from patients

with chronic fatigue

syndrome.

Somatomedin C (insulin-like

growth factor I) levels in

patients with chronic fatigue

syndrome.

Confronting AIDS in older

adults.

[Chronic fatigue syndrome.

To be or not to be][article in

Spanish]

[Attributions and chronic

fatigue].[article in Dutch]

Use of amantadine for

chronic fatigue syndrome.

J Clin Immunol 1997

Mar;17(2):160-6

J Psychiatr Res 1997 Jan-

Feb;31(1):91-6

N J Med 1997

Nov;94(11):39-41

Med Clin (Barc) 1997 Apr

19;108(15):577-9 Comment

on: Med Clin (Barc). 1997

Apr 19;108(15):561-5

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1510-

2Comment in: Ned Tijdschr

Geneeskd. 1997 Nov

29;141(48):2360 Ned

Tijdschr Geneeskd. 1997

Nov 29;141(48):2360-1

Arch Intern Med 1997 Jun

9;157(11):1264-5

where there is a lowering of energy levels and a loss of zest for life, or it may reveal the pathological aspect

of unresolved rage. Depending on the degree of pathological disturbance, working with and through the

rage may or may not result in a resolution of the symptoms of ME. In this paper I consider some of the

problems in the transference and countertransference relationship, which make it extremely difficult to

separate out reality from phantasy. There is then the further problem of the denial of the psyche by the

patient as part of the violence inherent in the illness. One case is presented, an example of ME in a

borderline male patient in whom resolution could not be achieved.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients

with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression,

systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and

the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta

levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01).

Additionally, no significant differences were found between the healthy control subjects and any of the

disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with

CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In

conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various

diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings

raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of

interest to examine if these two syndromes have pathogenetic as well as clinical features in common.

Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy

controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function

and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia

syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue

syndrome. Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from

49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin

C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2,

P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on

levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age. In contrast to

patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in

patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two

conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic

neuroendocrine axis.

A 57-year-old corporate executive, married with three grown children, began suffering from severe flu-like

symptoms and weight loss. Hospitalized for a week, he was tested for chronic fatigue syndrome and

mononucleosis. Finally, with no change in his symptoms, his physician recommended an HIV test. The

results were positive.

It was recently suggested that chronic fatigue is merely a question of attribution. Attribution clearly

contributes to the course of chronic fatigue syndrome (CFS) but is not its sole determinant. The presence of

strong somatic attributions appears to be one of the perpetuating factors in CFS but not the only one. Many

CFS patients present a self-diagnosis, e.g. myalgic encephalomyelitis. Communication problems between

patient and doctor easily arise because of different attributions of the complaints. At the start of fatigue

somatic attributions are of less importance than later on in the course of the complaints. In this process an

iatrogenic factor might be involved. On the other hand doctors are able to influence these attributions

actively in a favourable direction.


ME Research UK — Database of Research Publications 1997

Letter

Bruno RL

Buchwald D, Pearlman T,

Kith P, Katon W,

Schmaling K.

Buchwald D, Wener MH,

Pearlman T, Kith P.

Cannon JG, Angel JB,

Abad LW, Vannier E,

Mileno MD, Fagioli L,

Wolff SM, Komaroff AL.

Department of Medicine,

University of Washington,

Seattle, USA.

Department of Medicine,

University of Washington,

Seattle, USA.

Department of Medicine,

Tufts University-New

England Medical Center,

Boston, Massachusetts

02111, USA.

Chronic Fatigue, Fainting

and Autonomic Dysfunction:

Further Similarities Between

Post-Polio Fatigue and

Chronic Fatigue Syndrome

Screening for psychiatric

disorders in chronic fatigue

and chronic fatigue

syndrome.

Markers of inflammation and

immune activation in chronic

fatigue and chronic fatigue

syndrome.

Interleukin-1 beta,

interleukin-1 receptor

antagonist, and soluble

interleukin-1 receptor type II

secretion in chronic fatigue

syndrome.

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 109 -

116

J Psychosom Res 1997

Jan;42(1):87-94

J Rheumatol 1997

Feb;24(2):372-6

J Clin Immunol 1997

May;17(3):253-61

To test the hypothesis that fatigue and fainting occur together, 1,047 polio survivors and 419 non-disabled

control subjects were asked about the frequency and cause of fainting and asked to rate their typical daily

fatigue severity. Fatigue severity was significantly higher in polio survivors as compared to controls, and in

both polio survivors and controls who had fainted, as compared to those who had not. Daily fatigue severity

also increased in both groups as the number of lifetime faints increased. Fatigue was significantly higher in

controls who fainted one time and three times as compared to controls who had never fainted. Daily fatigue

severity was significantly higher in polio survivors who had fainted three, four and five times as compared

to those who had never fainted. These findings suggest a physiological relationship between fatigue and

fainting, possibly attributable to the close proximity of cardiovascular regulation and brain activation

centers within the brain stem. Fatigue and hypotension in patients with chronic fatigue syndrome and in

polio

Psychiatric disorders are common in chronic fatigue (CF) and chronic fatigue syndrome (CFS). To

determine the usefulness of the General Health Questionnaire (GHQ), a self-report measure of

psychological distress, in identifying those with psychiatric illnesses, a structured psychiatric interview and

the GHQ were administered to 120 CF and 161 CFS patients seen in a referral clinic. Overall, 87 (35%)

patients had a current and 210 (82%) a lifetime psychiatric disorder. Compared to patients without

psychiatric disorders, GHQ scores above the threshold (> or = 12) were more frequent among patients with

current (p < 0.001) and lifetime (p < 0.05) diagnoses; scores among patients with CF and CFS were similar.

Longer illness duration, greater fatigue severity, and current psychiatric disorders were significant

predictors of the GHQ score. In CF and CFS, the best sensitivity (0.69-0.76) and specificity (0.51-0.62)

were achieved for current psychiatric diagnoses using a threshold score of > or = 12. Thus, patients scoring

< 12 on the GHQ are significantly less likely to have a psychiatric disorder.

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation.

We examined the role of serum markers of inflammation and immune activation among patients with CFS

and in those with chronic fatigue (CF) not meeting the case definition. METHODS: Assays for soluble

interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed

in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria

for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on

examination. RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-

microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01).

Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those

without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not

observed. The presence of several markers was highly correlated (p < 0.01). CONCLUSION: Our findings

that levels of several markers were significantly correlated points to a subset of patients with immune

system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as

an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall,

serum markers of inflammation and immune activation are of limited diagnostic usefulness in the

evaluation of patients with CSF and CF.

Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often

exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which

include fatigue, myalgia, and low-grade fever, are similar to those experienced by patients infused with

cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular

secretion of interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), and soluble

interleukin-1 receptor type II (IL-1sRII) is abnormal in female CFS patients compared to age- and activitymatched

controls; (2) that these abnormalities may be evident only at certain times in the menstrual cycle;

and (3) that physical exertion (stepping up and down on a platform for 15 min) may accentuate differences

between these groups. Isolated peripheral blood mononuclear cells from healthy women, but not CFS

patients, exhibited significant menstrual cycle-related differences in IL-1 beta secretion that were related to

estradiol and progesterone levels (R2 = 0.65, P < 0.01). IL-1Ra secretion for CFS patients was twofold

higher than controls during the follicular phase (P = 0.023), but luteal-phase levels were similar between

groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients


ME Research UK — Database of Research Publications 1997

Cannon JG, St Pierre BA.

Chaudhuri A, T. Majeed,

T. Dinan, P. O. Behan

Chester AC, Levine PH.

Chester AC.

Chester AC.

Clauw DJ, Chrousos GP.

Intercollege Physiology

Program, Pennsylvania State

University, University Park

16802-6900, USA.

Georgetown University

Medical Center, Washington

DC, USA.

Georgetown University

Medical Center, Washington

D.C., USA.

Department of Medicine,

Georgetown University

Medical Center, Washington,

D.C. 20007, USA.

Gender differences in host

defense mechanisms.

Chronic Fatigue Syndrome A

Disorder of Central

Cholinergic Transmission

The natural history of

concurrent sick building

syndrome and chronic fatigue

syndrome.

Chronic fatigue syndrome

criteria in patients with other

forms of unexplained chronic

fatigue.

Neurally mediated

hypotension, chronic fatigue

syndrome and upper

aerodigestive tract reflexes.

Chronic pain and fatigue

syndromes: overlapping

clinical and neuroendocrine

features and potential

pathogenic mechanisms.

J Psychiatr Res 1997 Jan-

Feb;31(1):99-113

Journal of Chronic Fatigue

Syndrome 1997: 3(1): 3 - 16

J Psychiatr Res 1997 Jan-

Feb;31(1):51-7

J Psychiatr Res 1997 Jan-

Feb;31(1):45-50

Integr Physiol Behav Sci

1997 Apr-Jun;32(2):160-1

Neuroimmunomodulation

1997 May-Jun;4(3):134-53

compared to controls (P = 0.002). The only changes that might be attributable to exertion occurred in the

control subjects during the follicular phase, who exhibited an increase in IL-1 beta secretion 48 hr after the

stress (P = 0.020). These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients

that may be related to altered sensitivity to estradiol and progesterone. Furthermore, the increased release of

IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated

with chronic, low-level activation of the immune system.

Extensive studies in both humans and animals have shown that females express enhanced levels of

immunoreactivity compared to males. Whereas this provides females with increased resistance to many

types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on

gender-related differences in non-specific host defense mechanisms with a particular emphasis on

monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1).

Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally,

these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome

(CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in

immune function to find a key for this poorly understood syndrome.

No abstract available

An outbreak of chronic fatigue syndrome linked with sick building syndrome was recently described as a

new association. Whether chronic fatigue syndrome acquired in this setting tends to remit or, as sporadic

cases often do, persist, is unknown. To clarify the natural history of chronic fatigue syndrome in association

with sick building syndrome the 23 individuals involved in the outbreak were interviewed four years after

the onset. In the previous interview one year after the onset of symptoms, 15 (including 5 with chronic

fatigue syndrome and 10 with idiopathic chronic fatigue) of the 23 noted fatigue. Three years later 10 of the

15 were "fatigue free" or "much improved". Five were only "some better", "the same", or "worse". Three of

the five people previously diagnosed with chronic fatigue syndrome were "much improved" (two) or

"fatigue free" (one). The remaining two were seriously impaired, homebound and unable to work. The 10

individuals with substantially improved fatigue (three of the five with chronic fatigue syndrome and seven

of the 10 with idiopathic chronic fatigue) were more likely to have noted improvement in nasal and sinus

symptoms, sore throats, headaches, and tender cervical lymph nodes when compared to those with a

lingering significant fatigue (p < 0.001). Upper respiratory symptoms and headaches improved in those

with reduced fatigue but remained problematic in those with persisting significant fatigue. We conclude

that the fatigue related to sick building syndrome, including chronic fatigue syndrome, is significantly more

likely to improve than fatigue identified in sporadic cases of chronic fatigue syndrome.

To determine the prevalence of chronic fatigue syndrome (CFS) criteria in other forms of unexplained

chronic fatigue, 297 consecutive outpatients under the age of 40 from a general medicine practice were

studied. After excluding the three with chronic fatigue syndrome, the remaining 294 individuals were

divided into those with unexplained chronic fatigue (64 patients) those without (the remaining 230

patients). Chronic fatigue syndrome criteria noted to be significantly more common in those with

unexplained fatigue compared to those without include: fever, painful adenopathy, muscle weakness,

myalgia, headache, migratory arthralgia, neuropsychologic symptoms, and sleep disorder. Like chronic

fatigue syndrome, unexplained chronic fatigue often started suddenly. I conclude that the CFS criteria are

noted more commonly than expected in other forms of unexplained chronic fatigue.

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical

literature, although the terms used to describe these symptom complexes have changed frequently. The

currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which

describe the prominent clinical features of the illness without any attempt to identify the cause. This review

delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is


ME Research UK — Database of Research Publications 1997

Clauw DJ, Schmidt M,

Radulovic D, Singer A,

Katz P, Bresette J.

Clements A, Sharpe M,

Simkin S, Borrill J, Hawton

K.

Cuende JI, Civeira P, Diez

N, Prieto J.

Division of Rheumatology,

Immunology and Allergy,

Georgetown University

Medical Center, Washington,

D.C., USA.

Department of Psychiatry,

University of Oxford,

Warneford Hospital, UK.

alison.clements@psychiatry.

ox.ac.uk

Laboratorio de Biologia

Molecular, Hospital

Provincial San Telmo,

Palencia.

The relationship between

fibromyalgia and interstitial

cystitis.

Chronic fatigue syndrome: a

qualitative investigation of

patients' beliefs about the

illness.

[High prevalence without

reactivation of herpes virus 6

in subjects with chronic

fatigue syndrome].[article in

Spanish]

J Psychiatr Res 1997 Jan-

Feb;31(1):125-31

J Psychosom Res 1997

Jun;42(6):615-24

An Med Interna 1997

Sep;14(9):441-4

presented to demonstrate how genetic and environmental factors may interact to cause the development of

these syndromes, which we postulate are caused by central nervous system dysfunction. Various

components of the central nervous system appear to be involved, including the hypothalamic pituitary axes,

pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to

corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of

the illnesses. Review, Academic

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the

bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more

common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has

been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue

syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and

fibromyalgia respectively, both disorders share a number of features, including similar demographics,

"allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and

efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and

IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of

symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were

questioned regarding current symptomatology. A dolorimeter examination was also performed in the three

groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar

for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain

sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that

IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely

increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been

suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same

types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder.

The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have

found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is

physical in nature and minimize the role of psychological and social factors. There is also evidence that

patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by

questionnaire. The aim of this study was to explore the nature and origin of illness beliefs in more detail

using in-depth interviews and a qualitative analysis of patient responses. Sixty-six consecutive referrals

meeting Oxford criteria for chronic fatigue syndrome were recruited. Analysis of responses indicated that,

whereas the most commonly described explanation for the illness was a physical one, more than half the

patients also believed "stress" had played a role. Patients believed that they could partially control the

symptoms by reducing activity but felt helpless to influence the physical disease process and hence the

course of the illness. Patients reported that they had arrived at these beliefs about the illness after prolonged

reflection on their own experience combined with the reading of media reports, self help books, and patient

group literature. The views of health professionals played a relatively small role. There is potentially a

considerable opportunity to help patients arrive at a wider and more enabling explanation of their illness

when they first present to primary care.

INTRODUCTION: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology. Some viruses have

been associated with CFS etiology, specially herpesviruses, enteroviruses and retroviruses. Some studies

suggest an association between human herpesvirus-6 (HHV-6) and CFS. In order to know if there is an

active HHV-6 infection in CFS patients we studied the immunologic and virologic status of HHV-6.

MATERIALS AND METHODS: Twenty patients with CFS were studied. IgG and IgM anti HHV-6 were

determined by indirect immunofluorescence assay. DNA from serum and peripheral blood mononuclear

cells (PBMC) were studied by dot- and Southern-blotting and nested-PCR to detect HHV-6 DNA. HHV-6

RNA from PBMC were amplified by RT(retrotranscription)-PCR. RESULTS: Ten patients (50%) had IgG

anti-HHV-6 in serum but none had IgM anti-HHV-6. Dot-blotting of DNA from 200 microliters of serum

and Southern-blotting of 10 micrograms of PBMC DNA were negative. Nested-PCR from sera were

negative. Nested-PCR with 1 microgram PBMC DNA were positive in 8 out 20 (40%) and with 5

micrograms PBMC DNA were positive in 16 out of 20 (80%). No viral RNA were detected in PBMC.

CONCLUSIONS: There is a high proportion of CFS patients infected with HHV-6 but with low viral load.


ME Research UK — Database of Research Publications 1997

de Jong LW, Prins JB,

Fiselier TJ, Weemaes CM,

Meijer-van den Bergh EM,

Bleijenberg G.

de Loos WS.

De Lorenzo F, Hargreaves

J, Kakkar VV.

Deale A, Chalder T, Marks

I, Wessely S.

DeLuca J, Johnson SK,

Ellis SP, Natelson BH.

Afd. Medische Psychologie,

Academisch Ziekenhuis,

Nijmegen.

Department of Psychiatry,

Utrecht University Hospital,

The Netherlands.

Thrombosis Research

Institute, London, UK.

Academic Department of

Psychological Medicine,

King's College Hospital,

London, United Kingdom.

UMDNJ-New Jersey Medical

School, Newark, USA.

[Chronic fatigue syndrome in

young persons].[article in

Dutch]

Chronic fatigue syndrome:

fatigue of unknown origin.

Pathogenesis and

management of delayed

orthostatic hypotension in

patients with chronic fatigue

syndrome.

Cognitive behavior therapy

for chronic fatigue syndrome:

a randomized controlled trial.

Sudden vs gradual onset of

chronic fatigue syndrome

differentiates individuals on

cognitive and psychiatric

measures.

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1513-6

Eur J Clin Invest 1997

Apr;27(4):268-9

Clin Auton Res 1997

Aug;7(4):185-90

Am J Psychiatry 1997

Mar;154(3):408-14 comment

in: Am J Psychiatry. 1998

Oct;155(10):1461-2

J Psychiatr Res 1997 Jan-

Feb;31(1):83-90

Results do not support HHV-6 reactivation in CFS patients.

The prevalence of chronic fatigue syndrome (CFS) in teenagers is 10-20 per 100,000 inhabitants in the

Netherlands. The natural course of the disorder is not favourable according to the literature. Proposed

criteria for the diagnosis 'CFS' in adolescence are: absence of a physical explanation for the complaints, a

disabling fatigue for at least six months and prolonged school absenteeism or severe motor and social

disabilities. Exclusion criterion should be a psychiatric disorder. Factors that attribute to the persistence of

fatigue are somatic attributions, illness enhancing cognitions and behaviour of parents as well as physical

inactivity. The role of the physician and the role of parents can enhance the problems. The treatment should

focus on decreasing the somatic attributions, on reinforcement by the parents of healthy adolescent

behaviour, on the gradual increase of physical activity and on decreasing attention (including medical

attention) for the somatic complaints.

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported

previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with

CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with

CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and

Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53%

women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory

evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a

sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and

laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS.

After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an

abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did

not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those

CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma

renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with

those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p =

0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found

to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could

explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.

OBJECTIVE: Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a

randomized controlled trial. METHODS: Sixty patients with chronic fatigue syndrome were randomly

assigned to 13 sessions of either cognitive behavior therapy (graded activity and cognitive restructuring) or

relaxation. Outcome was evaluated by using measures of functional impairment, fatigue, mood, and global

improvement. RESULTS: Treatment was completed by 53 patients. Functional impairment and fatigue

improved more in the group that received cognitive behavior therapy. At final follow-up, 70% of the

completers in the cognitive behavior therapy group achieved good outcomes (substantial improvement in

physical functioning) compared with 19% of those in the relaxation group who completed treatment.

CONCLUSIONS: Cognitive behavior therapy was more effective than a relaxation control in the

management of patients with chronic fatigue syndrome. Improvements were sustained over 6 months of

follow-up. Randomized Controlled Trial

To examine the influence of mode of illness onset on psychiatric status and neuropsychological

performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms.

These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized

neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher

cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS

groups was examined. The rate of concurrent psychiatric disease was significantly greater in the CFSgradual

group relative to the CFS-sudden group. While both CFS groups showed a significant reduction in

information processing ability relative to controls, impairment in memory was more severe in the CFSsudden

group. Because of the significant heterogeneity of the CFS population, the need for subgroup


ME Research UK — Database of Research Publications 1997

DeLuca J, Johnson SK,

Ellis SP, Natelson BH.

Demitrack MA, Engleberg

NC.

Demitrack MA.

Derman W, Schwellnus

MP, Lambert MI, Emms

M, Sinclair-Smith C, Kirby

P, Noakes TD.

Dickinson CJ.

University of Medicine and

Dentistry of New Jersey, New

Jersey Medical School,

Newark, USA.

Indiana University School of

Medicine, Indianapolis,

USA.

Lilly Research Laboratories,

Lilly Corporate Center,

Indianapolis, IN 46285,

USA.

MRC/UCT Bioenergetics of

Exercise Research Unit,

University of Cape Town

Medical School, Sports

Science Institute of South

Africa, Newlands, South

Africa.

Wolfson Institute of

Preventive Medicine, St.

Bartholomew's & Royal

London School of Medicine

& Dentistry, London, UK.

Cognitive functioning is

impaired in patients with

chronic fatigue syndrome

devoid of psychiatric disease.

Chronic fatigue syndrome.

Neuroendocrine correlates of

chronic fatigue syndrome: a

brief review.

The 'worn-out athlete': a

clinical approach to chronic

fatigue in athletes.

Chronic fatigue syndrome--

aetiological aspects.

J Neurol Neurosurg

Psychiatry 1997

Feb;62(2):151-5

Curr Ther Endocrinol Metab

1997;6:152-60

J Psychiatr Res 1997 Jan-

Feb;31(1):69-82

J Sports Sci 1997

Jun;15(3):341-51

Eur J Clin Invest 1997

Apr;27(4):257-67Comment

in: Eur J Clin Invest. 1997

Apr;27(4):255-6 Eur J Clin

Invest. 1997

Dec;27(12):1061-2

analysis is discussed.

OBJECTIVE: To examine the effect of the presence or absence of psychiatric disease on cognitive

functioning in chronic fatigue syndrome. METHODS: Thirty six patients with chronic fatigue syndrome

and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue

syndrome sample were formed based on the presence or absence of comorbid axis I psychiatric disorders.

Patients with psychiatric disorders preceding the onset chronic fatigue syndrome were excluded. Subjects

were administered a battery of standardised neuropsychological tests as well as a structured psychiatric

interview. RESULTS: Patients with chronic fatigue syndrome without psychiatric comorbidity were

impaired relative to controls and patients with chronic fatigue syndrome with concurrent psychiatric disease

on tests of memory, attention, and information processing. CONCLUSION: Impaired cognition in chronic

fatigue syndrome cannot be explained solely by the presence of a psychiatric condition. Controlled Clinical

Trial

Chronic fatigue syndrome remains one of the more perplexing syndromes in contemporary clinical

medicine. One approach to understanding this condition has been to acknowledge its similarities to other

disorders of clearer pathophysiology. In this review, a rationale for the study of neuroendocrine correlates of

chronic fatigue syndrome is presented, based in part on the clinical observation that asthenic or fatigue

states share many of the somatic symptom characteristics seen in recognized endocrine disorders. Of

additional interest is the observation that psychological symptoms, particularly disturbances in mood and

anxiety, are equally prominent in this condition. At this time, several reports have provided replicated

evidence of disruptions in the integrity of the hypothalamic-pituitary-adrenal axis in patients with chronic

fatigue syndrome. It is notable that the pattern of the alteration in the stress response apparatus is not

reminiscent of the well-understood hypercortisolism of melancholic depression but, rather, suggests a

sustained inactivation od central nervous system components of this system. Recent work also implicates

alterations in central serotonergic tone in the overall pathophysiology of this finding. The implications of

these observations are far from clear, but they highlight the fact that, though chronic fatigue syndrome

overlaps with the well-described illness category of major depression, these are not identical clinical

conditions.

Chronic fatigue in the athletic population is a common but difficult diagnostic challenge for the sports

physician. While a degree of fatigue may be normal for any athlete during periods of high-volume training,

the clinician must be able to differentiate between this physiological fatigue and more prolonged, severe

fatigue which may be due to a pathological condition. As chronic fatigue can be the presenting symptom of

many curable and harmful diseases, medical conditions which cause chronic fatigue have to be excluded.

The clinician must then be able to differentiate between chronic fatigue associated with training or chronic

fatigue from other medical causes, and also between the chronic fatigue syndrome and the overtraining

syndrome. Once the clinician has excluded all of the above medical conditions which cause chronic fatigue

in athletes, a significant proportion of fatigued athletes remain without a diagnosis. Novel data indicate that

skeletal muscle disorders may play a role in the development of symptoms experienced by the athlete with

chronic fatigue. The histological findings from muscle biopsies of athletes suffering from the 'fatigued

athlete myopathic syndrome' are presented. We have designed a clinical approach to the diagnosis and

work-up of the athlete presenting with chronic fatigue. The strength of this approach is that it hinges on the

participation of a multidisciplinary team in the diagnosis and management of the athlete with chronic

fatigue. The athlete, coach, dietician, exercise physiologist and sport psychologist all play an important role

in enabling the physician to make the correct diagnosis.

The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions

have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition

there are no consistently abnormal physical signs or abnormalities on laboratory investigation. Many

physicians remain convinced that the symptoms are psychological rather than physical in origin. This view

is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms

between CFS and depression remains a source of confusion and difficulty. But even if all CFS patients were


ME Research UK — Database of Research Publications 1997

Dimitrov M , Jordan

Grafman

Dinan TG, Majeed T,

Lavelle E, Scott LV, Berti

C, Behan P.

Dobbins JG, Bonnie

Randall, Michele Reyes ,

Lea Steele, Elizabeth A.

Livens BA, William C.

Reeves

Department of Psychological

Medicine, St Bartholomew's

Hospital, London, UK.

T.G.Dinan@mds.qmw.ac.uk

Neuropsychological

Assessment of Chronic

Fatigue Syndrome

Blunted serotonin-mediated

activation of the

hypothalamic-pituitaryadrenal

axis in chronic

fatigue syndrome.

The Prevalence of Chronic

Fatiguing Illnesses Among

Adolescents in the United

States

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 31 - 42

Psychoneuroendocrinology

1997 May;22(4):261-7

Journal of Chronic Fatigue

Syndrome 1997: 3(2): 15 - 27

rediagnosed as depressives, this would not negate the possibility of an underlying organic cause for the

condition, in view of the growing evidence that depression itself has a physical cause and responds best to

physical treatments. There is some evidence both for active viral infection and for an immunological

disorder in the CFS. Many observations suggest that the syndrome could derive from residual damage to

the reticular activating system (RAS) of the upper brain stem and/or to its cortical projections. Such

damage could be produced by a previous viral infection, leaving functional defects unaccompanied by any

gross histological changes. In animal experiments activation of the RAS can change sleep state and activate

or stimulate cortical functions. RAS lesions can produce somnolence and apathy. Studies by modern

imaging techniques have not been entirely consistent, but many magnetic resonance imaging (MRI) studies

already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS.

Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more

consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar

lesions have been reported after poliomyelitis and in multiple sclerosis--in both of which conditions chronic

fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in

the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the

therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to

treatment can already be envisaged.

We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a

between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC

criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a

cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods

for ACTH and cortisol were drawn. They were then given ipsapirone 20 mg PO and further blood for

hormone estimation was taken at +30, +60, +90, +120 and +180 min. Baseline ACTH and cortisol levels

did not differ between the two groups. Release of ACTH (but not cortisol) in response to ipsapirone

challenge was significantly blunted in patients with CFS. We conclude that serotonergic activation of the

hypothalamic-pituitary-adrenal axis is defective in CFS. This defect may be of pathophysiological

significance.

Objective. To compare the prevalence of unexplained chronic fatigue (CF) and chronic fatigue syndrome

(CFS) among adolescents in three studies conducted by the Centers for Disease Control and Prevention and

to compare these estimates with those for adults in two of the studies. Design. Thc studies used the

following three designs: (i) a physicianbased CFS surveillance system, (ii) a random, cross-sectional

community telephone survey and (iii) a cross-sectional survey of school nurses. Setting. Surveillance

included all patients with unexplained fatigue seen by participating physicians in four communities over a

2-year period; the community survey was conducted in a defined, urban population; and the survey of

nurses included all middle, junior, and high school nurses in two communities. Patients or other

participants. Twenty-three adolescent cases of unexplained chronic fatiguing illness were reported to the

surveillance system, 7 of whom were classified with CFS. The community survey screened 2,249 persons

between the ages of 2 and 17 years and identified 5 with unexplained chronic fatiguing illness, only one of

whom might have had CFS. The school nurses identified 22 students with unexplained fatiguing illness, 10

of whom had received a diagnosis of CFS. Main outcome measures. The prevalence of unexplained chronic

fatiguing illness was estimated in all three studies. The prevalence of CFS was estimated in one study, the

prevalence of CFS-like illness was estimated in another, and the prevalence of a reported diagnosis of CFS

was estimated in the third. Results. In general, the prevalence estimates of CF, CFS-like illness, and CFS

for adolescents were lower than those for adults. One study also included children ages 2 to 11 years and

found very little CF and no CFS. Cases of CFS among adolescents were evenly distributed across

individual years of age. Conclusions. CFS was clearly present among adolescents, although the prevalence

for this group was lower than for most adult age groups: Differences in prevalence estimates among the

three studies were consistent with differences in study designs. The validity of adolescent/adult

comparisons within each study should not be affected by the study design. Further study of the applicability


ME Research UK — Database of Research Publications 1997

Dowsett EG, Colby J.

Dowsett EG, Jane Colby

Droge W, Holm E.

Durlach J, Bac P, Durlach

V, Bara M, Guiet-Bara A.

Division of

Immunochemistry, Deutsches

Krebsforschungszentrum,

Heidelberg, Germany.

SDRM, Hopital Saint-

Vincent-de-Paul, Paris.

Chronic fatigue syndrome in

children. Journal was wrong

to critizise study in

schoolchildren.

Long-Term Sickness

Absence Due to ME/CFS in

UK Schools An

Epidemiological Study with

Medical and Educational

Implications

Role of cysteine and

glutathione in HIV infection

and other diseases associated

with muscle wasting and

immunological dysfunction.

Neurotic, neuromuscular and

autonomic nervous form of

magnesium imbalance.

BMJ 1997 Oct

11;315(7113):949 Comment

on: BMJ. 1997 Jun

7;314(7095):1635-6

Journal of Chronic Fatigue

Syndrome 1997: 3(2): 29 - 42

FASEB J 1997

Nov;11(13):1077-89

Magnes Res 1997

Jun;10(2):169-95

of the current CFS case definition to adolescents is warranted.

A study was made to determine whether the recognition of multiple cases of myalgic

encephalomyelitis/chronic fatigue syndrome (ME/CFS) in one school is a unique experience. A five-year

retrospective period prevalence survey (1991-1995) was collated from sequential reports made in six

English Local Education Authority (LEA) areas. By means of a confidential questionnaire circulated to

2,942 school principals via internal mail, 1,098 schools, comprising 27,327 staff and 333,024 pupils, were

investigated. Details were obtained on age, gender, location in school sector, work pattern and morbidity.

Forty-two percent of all medically certified long-term sickness absence was ascribed to ME/CFS, this figure

being well in excess of all other causes. This diagnosis was significantly associated with case clustering,

variable geographical prevalence, a marked increase in the female:male case ratio at puberty and prolonged

disturbance of educational potential. We conclude that ME/CFS in schools leads to serious economic and

career problems. Redirection of research to special educational needs and to early diagnosis of infectious

agents which can trigger ME/CFS in schools might prevent, at low cost, much chronic illness and education

deficit.

The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell

activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a

complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in

patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic

fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in

diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases

is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially

stable balance between the immune system and virus, and trigger disease progression. This hypothesis is

supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma

cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione

in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated

primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a

physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit

is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be

a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.

Review, Academic

The nervous form of magnesium imbalance represents the best documented experimental and clinical

aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears

as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and

therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results

in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms,

analogous to the symptomatology previously described in medical literature as latent tetany,

hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and

idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular

hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign,

but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the

precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which

is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram

(EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the

three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three

facilitation procedures: tourniquet-induced ischaemia lasting 10 min. post-ischaemia lasting 10 min after

the removal of the tourniquet and hyperventilation over 5 min. A repetitive EMG constitutes the principal

mark of nervous hyperexcitability (NHE) due to MD. The echocardiogram (ECC) is the best tool for

detecting MVP, the 2-dimensional ECC with pulsed Doppler being more accurate than time-motion ECC.


ME Research UK — Database of Research Publications 1997

Egyedi P.

Elliot DL, Goldberg L,

Loveless MO.

Evengard B, Lipkin WI.

Fairhurst D, Waterman M,

Lynch S.

Field TM, William

Sunshine , Maria

Hernandez-Reif , Olga

Quintino BS, Saul

Schanberg , Cynthia Kuhn

, Iris Burman

Fiore G, Giacovazzo F,

Giacovazzo M.

Institutionen for

infektionssjukdomar,

mikrobiologi, patologi och

immunologi, Huddinge

sjukhus.

VI Cattedra di Medicina

Interna, Universita La

[Chronic fatigue

syndrome].[article in Dutch]

Graded exercise testing and

chronic fatigue syndrome.

[A known virus in animals is

suspected in humans. Borna

disease virus has been

detected in human

neuropathy].[article in

Swedish]

Cognitive slowing in chronic

fatigue syndrome (CFS)

Massage Therapy Effects on

Depression and Somatic

Symptoms in Chronic

Fatigue Syndrome

Three cases of

dermatomyositis erroneously

Ned Tijdschr Geneeskd 1997

Sep 13;141(37):1790-1

Am J Med 1997

Jul;103(1):84-6 Comment

on: Am J Med. 1996

Jun;100(6):634-40

Lakartidningen 1997 Dec

10;94(50):4753-6

Psychosom Med 1997 Nov-

Dec;59(6):638 Comment on:

Psychosom Med. 1997 Jan-

Feb;59(1):58-66

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 43 - 51

Eur Rev Med Pharmacol Sci

1997 Nov-Dec;1(6):193-5

The routine ionic investigations comprise five static tests: plasma and erythrocyte magnesium, plasma

calcium and daily magnesiuria and calciuria. An evaluation of magnesium intake is desirable. Normal

concentrations of magnesium in blood do not rule out the diagnosis of the nervous form of primary chronic

MD. The histograms of MD group reveal Gaussian type magnesaemias with significantly lower means and

the constituent elements can be individually hypo- (one-third of cases), normo- (about two-thirds of cases)

and even, exceptionally, hyper-magnesaemic. The diagnosis of MD requires an oral magnesium load test.

At physiological dose (5 mg of Mg/kg/day), oral magnesium is totally devoid of the pharmacological

effects of parenteral magnesium. Corrections of symptomatology by this oral physiological magnesium load

is the best proof that it was due to magnesium deficiency. In particular clinical forms, more sophisticated

studies may be useful: standard and quantitative electroencephalograms, electropolygraphic studies of

afternoon sleep, electronystagmography, optokinetic test, skin conductance reflex, psychometric

inventories, standard or monitoring electrocardiogram, treadmill test, other static and dynamic

investigations: e.g. ionized free Mg2+, lymphocyte Mg, brain Mg, cerebrospinal Mg, Mg balance, Mg

parenteral load test, glucose load, and even radio-isotope study, the only one able to reveal intestinal

magnesium hypersecretion. Nervous primary chronic MD progresses by phases of decompensation against

a background of latency. Marginal magnesium deficiency, that is to say an insufficient magnesium intake

which merely requires simple oral physiological supplementation, is fundamental in the aetiology of

primary magnesium deficit. However a constitutional homeostatic lability of the nervous system or of

magnesium metabolism such as belonging to the B35 type of HLA group must be involved. Part of the

aetiology of this magnesium deficit is a magnesium depletion, where the disorder which induces

magnesium deficit is related to a dysregulation of the control mechanisms of magnesium status which

requires a more or less difficult Review, Academic

Borna disease virus (BDV) is a newly classified non-segmented neurotrophic negative-strand RNA virus

with a worldwide distribution and affecting warm-blooded animals ranging from birds to primates.

Infection may be asymptomatic or results in manifest disturbances of movement behaviour. Although BDV

has not been unequivocally implicated in any human disease, several reports have suggested relationship to

exist between BDV infection and certain neuropsychiatric syndromes including affective disorders, chronic

fatigue syndrome, and schizophrenia. Moreover, at least one centre has initiated a trial of antiviral therapy

in patients with affective disorders attributable to BDV. The article consists in a review of recent advances

in the molecular biology, pathogenesis and epidemiology of BDV, and an outline of anticipated directions

for future research.

Subsequent to recent reports of psychomotor retardation in chronic fatigue syndrome (CFS), the present

study investigated the relative contributions of cognitive and motor components to psychomotor

functioning in CFS. These components were differentiated by means of a reaction time paradigm proposed

by Cornell, Suarez and Berent (1). The relationship between the cognitive and motor components of

psychomotor performance and subjective cognitive and motor complaints was also investigated. Three

groups of subjects participated in the study: an experimental group comprised of ten patients with CFS, and

two comparison groups comprised of ten depressed and ten healthy individuals. Although the results of this

study are suggestive of minimal functional impairment in CFS, they implicate motor factors in

psychomotor slowing in unmedicated CFS patients

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.


ME Research UK — Database of Research Publications 1997

Fischler B, Cluydts R, De

Gucht Y, Kaufman L, De

Meirleir K.

Fischler B, Dendale P,

Michiels V, Cluydts R,

Kaufman L, De Meirleir K.

Fischler B, Le Bon O,

Hoffmann G, Cluydts R,

Kaufman L, De Meirleir K.

Fisher L.

Fitzgibbon EJ, Murphy D,

O'Shea K, Kelleher C.

Sapienza, Roma, Italy.

Department of Psychiatry,

Academic Hospital, Brussels,

Balgium.

Department of Psychiatry,

Academic Hospital, Free

University of Brussels,

Belgium.

Department of Psychiatry,

Academic Hospital, Free

University of Brussels,

Belgium.

Department of Psychological

Medicine, King's College

Hospital, London.

Publication Types: Review

Review, Tutorial

Department of Health

Promotion, University

College Galway, Ireland.

diagnosed as "chronic fatigue

syndrome".

Generalized anxiety disorder

in chronic fatigue syndrome.

Physical fatigability and

exercise capacity in chronic

fatigue syndrome: association

with disability, somatization

and psychopathology.

Sleep anomalies in the

chronic fatigue syndrome. A

comorbidity study.

Acta Psychiatr Scand 1997

May;95(5):405-13

J Psychosom Res 1997

Apr;42(4):369-78

Neuropsychobiology

1997;35(3):115-22

Chronic fatigue syndrome. Prof Nurse 1997

May;12(8):578-81Comment

in: Prof Nurse. 1997

Aug;12(11):827

Chronic debilitating fatigue

in Irish general practice: a

survey of general

practitioners' experience.

Br J Gen Pract 1997

Oct;47(423):618-22

A structured psychiatric interview, forming part of a global psychopathological approach, revealed higher

prevalence rates of current and lifetime psychiatric disorders and a higher degree of psychiatric comorbidity

in patients with chronic fatigue syndrome (CFS) than in a medical control group. In contrast to previous

studies, a very high prevalence of generalized anxiety disorder (GAD) was found in CFS, characterized by

an early onset and a high rate of psychiatric comorbidity. It is postulated that GAD represents a

susceptibility factor for the development of CFS. A significantly higher prevalence was also observed for

the somatization disorder (SD) in the CFS group. Apart from a higher female-to-male ratio in fibromyalgia,

no marked differences were observed in sociodemographic or illness-related features, or in psychiatric

morbidity, between CFS patients with and without fibromyalgia. CFS patients with SD have a longer illness

duration and a higher rate of psychiatric comorbidity. These findings are consistent with the suggestion of

Hickie et al. (1) that chronic fatigued subjects with SD should be distinguished from subjects with CFS.

Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were

assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart

rate, THR) during incremental exercise. The association with functional status impairment, somatization,

and psychopathology was examined. A statistically significant association was demonstrated between this

physical fatigability variable and impairment, and a trend was found for an association with somatization.

No association was demonstrated with psychopathology. These results are in accordance with the cognitivebehavioral

model of CFS, suggesting a major contribution of avoidance behavior to functional status

impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior.

Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical

deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup.

Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding

argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic

metabolism during effort.

Polysomnographic findings were compared between a group of patients with the chronic fatigue syndrome

(CFS; n = 49) and a matched healthy control (HC) group (n = 20). Sleep initiation and sleep maintenance

disturbances were observed in the CFS group. The percentage of stage 4 was significantly lower in the CFS

group. A discriminant analysis allowed a high level of correct classification of CFS subjects and HC. Sleeponset

latency and the number of stage shifts/hour contributed significantly to the discriminant function. The

presence of these anomalies as well as the decrease in stage 4 sleep were not limited to the patients also

diagnosed with fibromyalgia or with a psychiatric disorder. No association was found between sleep

disorders and the degree of functional status impairment. The mean REM latency and the percentage of

subjects with a shortened REM latency were similar in CFS and HC.

BACKGROUND: Doctors are called upon to treat chronic debilitating fatigue without the help of a

protocol of care. AIMS: To estimate the incidence of chronic debilitating fatigue in Irish general practice, to

obtain information on management strategy and outcome, to explore the attitudes of practitioners (GPs)

towards the concept of a chronic fatigue syndrome (CFS), and to recruit practitioners to a prospective study

of chronic fatigue in primary care. METHOD: A total of 200 names were selected from the database of the

Irish College of General Practitioners (ICGP); 164 of these were eligible for the study. RESULTS:

Altogether, 118 questionnaires were returned (72%). Ninety-two (78%) responders identified cases of

chronic fatigue, giving an estimated 2.1 cases per practice and an incidence of 1 per 1000 population. All

social classes were represented, with a male to female ratio of 1:2. Eleven disparate approaches to treatment

were advocated. Many (38%) were dissatisfied with the quality of care delivered, and 45% seldom or hardly

ever referred cases for specialist opinion. The majority (58%) accepted CFS as a distinct entity, 34% were

undecided, and 8% rejected it. Forty-two (35%) GPs volunteered for a prospective study. CONCLUSION:


ME Research UK — Database of Research Publications 1997

Fohlman J, Friman G,

Tuvemo T.

Franklin AJ.

Freeman R, Komaroff AL.

Fukuda K, Dobbins JG,

Wilson LJ, Dunn RA,

Wilcox K, Smallwood D.

Infektionskliniken,

Akademiska sjukhuset,

Uppsala.

Department of Neurology,

Beth Israel Deaconess

Medical Center, Boston,

Massachusetts 02215, USA.

Division of Viral and

Rickettsial Diseases, Centers

for Disease Control and

Prevention, Atlanta, GA

30333, USA.

[Enterovirus infections in

new disguise].[article in

Swedish]

Graded exercise in chronic

fatigue syndrome. Including

patients who rated

themselves as a little better

would have altered results.

Does the chronic fatigue

syndrome involve the

autonomic nervous system

An epidemiologic study of

fatigue with relevance for the

chronic fatigue syndrome.

Lakartidningen 1997 Jul

9;94(28-29):2555-60

BMJ 1997 Oct

11;315(7113):947;

discussion 948 Comment on:

BMJ. 1997 Jun

7;314(7095):1635-6 BMJ.

1997 Jun 7;314(7095):1647-

52

Am J Med 1997

Apr;102(4):357-64

J Psychiatr Res 1997 Jan-

Feb;31(1):19-29

Chronic fatigue is found in Irish general practice among patients of both sexes and all social classes.

Doctors differ considerably in their management of patients and are dissatisfied with the quality of care

they deliver. Many cases are not referred for specialist opinion. A prospective database is required to

accurately assess the scale of this public health problem and to develop a protocol of care.

Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses,

picomavirus, which are widespread in nature. Enteroviruses cause a number of wellknown diseases and

symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The

development of polio vaccines is the greatest accomplishment within the field of enterovirus research and

the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play

a more important part in the morbidity panorama than was previously thought. Chronic (persistent)

enteroviruses were formerly unknown. Serologic and molecular biology techniques have now demonstrated

that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent).

Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might

contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio

syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue

syndrome.

PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with

chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and

predisposition to neurally mediated syncope reported in this patient group. PATIENTS AND METHODS:

Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients

completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and

premorbid and coexisting psychiatric disorders. The relationship between autonomic test results,

cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the

evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic

neuropathy was explored. RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01)

and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous

system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P <

0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function

(systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P <

0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twentyfive

percent of CFS subjects had a positive tilt table test. The physical activity index was a significant

predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the

blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent

psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral

infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic

neuropathy. CONCLUSION: Patients with CFS show alterations in measures of sympathetic and

parasympathetic nervous system function. These results, which provide the physiological basis for the

orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained

by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.

We surveyed households in four rural Michigan communities to confirm a reported cluster of cases

resembling chronic fatigue syndrome (CFS) and to study the epidemiology of fatigue in a rural area. Data

were collected from 1698 households. We did not confirm the reported cluster. The prevalence of

households containing at least one fatigued person was similar between communities thought to harbor the

cluster and communities selected for comparison. Symptoms and features of generic forms of fatigue were

very similar to those often attributed to CFS.


ME Research UK — Database of Research Publications 1997

Fulcher KY, White PD.

Galbraith DN, Nairn C,

Clements GB.

Gaudino EA, Coyle PK,

Krupp LB.

National Sports Medicine

Institute, St Bartholomew's,

London.

Regional Virus Laboratory,

Ruchill Hospital, Glasgow,

UK.

Department of Neurology,

State University of New York

at Stony Brook, USA.

Randomised controlled trial

of graded exercise in patients

with the chronic fatigue

syndrome.

Evidence for enteroviral

persistence in humans.

Post-Lyme syndrome and

chronic fatigue syndrome.

Neuropsychiatric similarities

and differences.

BMJ 1997 Jun

7;314(7095):1647-

52Comment in: BMJ. 1997

Jun 7;314(7095):1635-6

BMJ. 1997 Oct

11;315(7113):947-8 BMJ.

1997 Oct 11;315(7113):947;

discussion 948 BMJ. 1997

Oct 11;315(7113):948

J Gen Virol 1997 Feb;78 ( Pt

2):307-12

Arch Neurol 1997

Nov;54(11):1372-6

Gloss TL The Legal Perspective Journal of Chronic Fatigue

Syndrome 1997: 3(4): 57 - 61

Goldberg MJ, Ismael

Mena, Jacques Darcourt

NeuroSPECT Findings in

Children - with Chronic

Fatigue Syndrome

Journal of Chronic Fatigue

Syndrome 1997: 3(1): 61 - 67

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome.

DESIGN: Randomised controlled trial with control treatment crossover after the first follow up

examination. SETTING: Chronic fatigue clinic in a general hospital department of psychiatry. SUBJECTS:

66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep

disturbance. INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or

flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited

to cross over to the exercise programme afterwards. MAIN OUTCOME MEASURE: The self rated clinical

global impression change score, "very much better" or "much better" being considered as clinically

important. RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out

before completion. 15 of 29 patients rated themselves as better after completing exercise treatment

compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave

similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly

better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after

flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated

themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated

themselves as better one year after completing supervised exercise treatment. CONCLUSION: These

findings support the use of appropriately prescribed graded aerobic exercise in the management of patients

with the chronic fatigue syndrome. Randomized Controlled Trial

We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue

syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at

least 5 months apart. The nucleotide sequence of the 5' non-translated region (bases 174-423) was

determined for each amplicon. Four individuals had virtually identical nucleotide sequences ( > 97%) in

both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had

persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses.

In the remaining three individuals, the lack of unique shared features suggested that re-infection had

occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is

related to the Coxsackie B-like viruses.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) and post-Lyme syndrome (PLS) share

many features, including symptoms of severe fatigue and cognitive difficulty. OBJECTIVE: To examine

the neuropsychiatric differences in these disorders to enhance understanding of how mood, fatigue, and

cognitive performance interrelate in chronic illness. METHODS: Twenty-five patients with CFS, 38

patients with PLS, and 56 healthy controls participated in the study. Patients with CFS met 1994 criteria for

CFS and lacked histories suggestive of Lyme disease. Patients with PLS were seropositive for Lyme

disease, had met the Centers for Disease Control and Prevention criteria, or had histories strongly

suggestive of Lyme disease and were experiencing severe fatigue that continued 6 months or more

following completion of antibiotic treatment for Lyme disease. All subjects completed self-report measures

of somatic symptoms and mood disturbance and underwent neuropsychological testing. All patients also

underwent a structured psychiatric interview. RESULTS: Patients with CFS and PLS were similar in

several somatic symptoms and in psychiatric profile. Patients with CFS reported more flulike symptoms

than patients with PLS. Patients with PLS but not patients with CFS performed significantly worse than

controls on tests of attention, verbal memory, verbal fluency, and motor speed. Patients with PLS without a

premorbid history of psychiatric illness did relatively worse on cognitive tests than patients with PLS with

premorbid psychiatric illness compared with healthy controls. CONCLUSIONS: Despite symptom overlap,

patients with PLS show greater cognitive deficits than patients with CFS compared with healthy controls.

This is particularly apparent among patients with PLS who lack premorbid psychiatric illness.

Background NeuroSPECT studies have described specific abnormalities in cerebral perfusion in adults with

criteria for Chronic Fatigue Syndrome. This reports findings in 13 children with criteria for Chronic Fatigue

Syndrome. Objective. NeuroSPECT findings in 13 CFS/CFIDS children. Methods. Thirteen children

meeting CDC criteria for CFS/CFIDS, were evaluated using NeuroSPECT imaging utilizing Xenon 133 and

Tc-99m-HMPAO (1). Results. In 13 children, hypoperfusion was observed at 42 ± 10 ml/min/100g, p


ME Research UK — Database of Research Publications 1997

Goldenberg DL.

Goudsmit EM.

Greco A, Tannock C,

Brostoff J, Costa DC.

Gregg VH.

Gupta S, Aggarwal S, See

D, Starr A.

Harmon DL, McMaster D,

McCluskey DR, Shields D,

Whitehead AS.

MRI Department, Centre

Hospitalier Princesse Grace,

Principality of Monaco.

Department of Psychology,

Birkbeck College, London,

UK.

Department of Medicine,

University of California,

Irvine 92717, USA.

Department of Genetics,

Trinity College, Dublin,

Ireland.

Fibromyalgia, chronic fatigue

syndrome, and myofascial

pain syndrome.

Graded exercise in chronic

fatigue syndrome. Chronic

fatigue syndrome is

heterogeneous condition.

Brain MR in chronic fatigue

syndrome.

Hypnosis in chronic fatigue

syndrome.

Cytokine production by

adherent and non-adherent

mononuclear cells in chronic

fatigue syndrome.

A common genetic variant

affecting folate metabolism is

not over-represented in

chronic fatigue syndrome.

Curr Opin Rheumatol 1997

Mar;9(2):135-43

BMJ 1997 Oct

11;315(7113):948 Comment

on: BMJ. 1997 Jun

7;314(7095):1647-52

AJNR Am J Neuroradiol

1997 Aug;18(7):1265-9

J R Soc Med 1997

Dec;90(12):682-3

J Psychiatr Res 1997 Jan-

Feb;31(1):149-56

Ann Clin Biochem 1997

Jul;34 ( Pt 4):427-9

Hedrick TE. Chronic fatigue syndrome. QJM 1997 Nov;90(11):723-5

Comment on: QJM. 1997

Mar;90(3):223-33

0.0001 in the left temporal lobe and at 45 ± 11, p < .001 in right temporal lobe. Statistically significant

hypoperfusion was also observed in both parietal lobes and at 50 and 53 ml/ min/100g, p < 0.05 in the

frontal lobe of the right hemisphere. Quantitatcd HMPAO demonstrated bilateral orbitofrontal and anterior

temporal hypoperfusion. There was also hypoperfusion in the dorsal aspects of both frontal lobes and both

parietooccipital lobes. Conclusion. NeuroSPECT is presented as a quantifiable, reproducible tool that can

allow us to document a cohort of children defined as CFS/CFIDS.

The diagnosis of fibromyalgia continues to generate heated debate. The presence of multiple lifetime

psychiatric diagnoses was not intrinsically related to fibromyalgia but rather to the decision of patients to

seek specialty medical care. Better outcome measures in fibromyalgia were tested. Neurally mediated

hypotension may be associated with chronic fatigue syndrome (CFS). Treatment of patients with

fibromyalgia and CFS continues to be of limited success, although the role of multidisciplinary group

intervention appears promising. Two position papers focused on the adverse aspects of the medicolegal

issues in fibromyalgia and CFS.

PURPOSE: To determine the prevalence of MR white matter abnormalities in patients with chronic fatigue

syndrome (CFS). METHODS: Brain MR studies of 43 patients (29 women and 14 men, 22 to 78 years old)

with a clinical diagnosis of CFS (n = 15), CFS with associated depression (n = 14), and CFS with

associated other psychiatric disorders, namely, anxiety and somatization disorder (n = 14), were compared

with brain MR studies in 43 age- and sex-matched control subjects. RESULTS: MR findings were

abnormal in 13 (32%) of the patients in the study group (ages 34 to 78 years) and in 12 (28%) of the

control subjects (ages 26 to 73 years). One patient with CFS had multiple areas of demyelination in the

supratentorial periventricular white matter. Another patient with CFS and associated depression had a

single focus of probable demyelination in the supratentorial periventricular white matter. In four patients

with CFS (ages 34 to 48 years) MR abnormalities consisted of one or several punctate hyperintense foci in

the corona radiata, centrum ovale, and frontal white matter. The remaining seven patients (ages 50 to 78

years) had frontoparietal subcortical white matter foci of high T2 signal. The prevalence of white matter

hyperintensities was not different between the patients and the control subjects. CONCLUSIONS: Our

findings suggest that no MR pattern of white matter abnormalities is specific to CFS.

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue

syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells

were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS),

respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also

measured at the mRNA level by polymerase chain reaction. The levels of spontaneously (unstimulated)

produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent

monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously

studied matched controls. The abnormality of IL-6 was also observed at mRNA level. In contrast,

spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent

cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may

play a role in the pathogenesis and in some of the clinical manifestations of CFS.


ME Research UK — Database of Research Publications 1997

Heyll U, Wachauf P,

Senger V, Diewitz M.

Holland P.

Holmes MJ, Diack DS,

Easingwood RA, Cross JP,

Carlisle B.

Houde SC, Kampfe-

Leacher R.

Hume M.

Jacobs G.

Jacobson SK, Daly JS,

Thorne GM, McIntosh K.

Gesellschaftsarztliche

Abteilung der Deutschen

Krankenversicherung, Koln.

Psychotherapy Department,

Royal Edinburgh Hospital.

Department of Microbiology,

University of Otago,

Dunedin, New Zealand.

mike.holmes@stonebow.otag

o.ac.nz

MGH Institute of Health

Professions, Boston, Mass,

USA.

Department of Pediatrics,

Harvard Medical School,

Boston, Massachusetts, USA.

[Definition of "chronic

fatigue syndrome"

(CFS)].[article in German]

Coniunctio--in bodily and

psychic modes: dissociation,

devitalization and integration

in a case of chronic fatigue

syndrome.

Electron microscopic

immunocytological profiles

in chronic fatigue syndrome.

Chronic fatigue syndrome: an

update for clinicians in

primary care.

Chronic fatigue syndrome in

children. All studies must be

subjected to rigorous

scrutiny.

Chronic fatigue syndrome in

children. Patient

organisations are denied a

voice.

Chronic parvovirus B19

infection resulting in chronic

fatigue syndrome: case

history and review.

Med Klin 1997 Apr

15;92(4):221-7

J Anal Psychol 1997

Apr;42(2):217-36

J Psychiatr Res 1997 Jan-

Feb;31(1):115-22

Nurse Pract 1997

Jul;22(7):30, 35-6, 39-40

passim

BMJ 1997 Oct

11;315(7113):949

BMJ 1997 Oct

11;315(7113):949 Comment

on: BMJ. 1997 Jun

7;314(7095):1635-6

Clin Infect Dis 1997

Jun;24(6):1048-51

The definition of "Chronic Fatigue Syndrome" (CFS) in 1988 was an attempt to establish a uniform basis

for the previously heterogeneous approaches to research of this severe and inexplicable state of fatigue. At

the same time, researchers wished to narrow down a pathogenetically founded disease entity a priori by

specifying precise disease criteria. The empirical data gathered in accordance with the CFS definition,

however, have failed to confirm the assumption that the disease entity is pathogenetically uniform.

Furthermore, the originally selected criteria have proven to be impracticable ore theoretically questionable.

In the period that followed, modifications that permitted a more comprehensive and yet more differentiated

classification of fatigue states of unclear etiology were proposed. The new research approach avoids

postulation of causal entities and puts CFS back in a category with other descriptive states of fatigue.

Three years of analytical psychotherapy with a professional woman in mid-life, suffering from chronic

fatigue syndrome (CFS), is described. Gradual recovery merged into mid-life changes; marriage, along with

a new balance of maternal and paternal imagos, enabled her to trust enough to become pregnant-coniunctio

in the most primal bodily and psychic modes. Her life-long, schizoid type pattern, "the pendulum of

closeness and isolation', with its extreme of psycho-physical collapse and devitalization, was replayed in

therapy. The analyst's symbolic attitude is emphasized, containing the patient's initial affective explosion

and validating the physicality of her condition. Mirroring and steady rhythmic attunement became a new,

pre-verbal, source of trust-vitalization; differentiation and separation replaced defensive splitting and

dissociation. Then the overwhelmingly powerful bodily/maternal could be counterbalanced by the

masculine, and a transitional space emerged for symbolic work. Both the regressive and the dynamic

aspects of CFS are located in the earliest undifferentiated, archetypal, bodily/psychic modes, when the

frustration of primary needs evokes the defences of the self. It is argued that our psychodynamic

understanding can contribute to the stalemate in seeing chronic fatigue syndrome as either an organic

illness or depression, and that a new linking of the somatic and psychic calls for a new professional

collaboration.

Structures consistent in size, shape and character with various stages of a Lentivirus replicative cycle were

observed by electron microscopy in 12-day peripheral-blood lymphocyte cultures from 10 of 17 Chronic

Fatigue Syndrome patients and not in controls. Attempts to identify a lymphoid phenotype containing these

structures by immunogold labelling failed and the results of reverse-transcriptase assay of culture

supernatants were equivocal. The study was blind and case-controlled, patients being paired with age, sex

and ethnically matched healthy volunteers. Prescreening of subjects included the common metabolic and

immunological disorders, functional conditions and a virus-screen against hepatitis B and C, Epstein-Barr

Virus, Cytomegalovirus and Human Immunodeficiency Virus.

Cases of long-standing (6 months or longer) fatigue that are not explained by an existing medical or

psychiatric diagnosis are referred to as chronic fatigue syndrome (CFS). CFS is a condition of unknown

etiology that presents with a complex array of symptoms in patients with diverse health histories. A

diagnosis of CFS is largely dependent upon ruling out other organic and psychologic causes of fatigue. CFS

can present the clinician with a unique set of challenges in terms of diagnosis and treatment. A review of

recent research suggests that the management of CFS requires an individualized approach for each patient.

An historic overview of the condition is presented along with current theories of causation, diagnosis

considerations, symptom management, and health promotion strategies. Review Literature

The spectrum of disease caused by parvovirus B19 has been expanding in recent years because of improved

and more sensitive methods of detection. There is evidence to suggest that chronic infection occurs in

patients who are not detectably immunosuppressed. We report the case of a young woman with recurrent

fever and a syndrome indistinguishable from chronic fatigue syndrome. After extensive investigation, we


ME Research UK — Database of Research Publications 1997

Jason LA, Michael T.

Ropacki, Nicole B. Santoro,

Judith A. Richman , Wendy

Heatherly, Renee Taylor,

Joseph R. Ferrari , Trina

M. Haney-Davis BA, Alfred

Rademaker , Josée Dupuis ,

Jacqueline Golding ,

Audrius V. Plioplys Sigita

Plioplys

Jason LA, Richman JA,

Friedberg F, Wagner L,

Taylor R, Jordan KM.

Jason LA, Tryon WW,

Frankenberry E, King C.

Jordan KM, Amy M.

Kolak, Leonard A. Jason

Joyce J, Hotopf M, Wessely

S.

Department of Psychology,

DePaul University, Chicago,

IL 60614, USA.

Department of Psychology,

DePaul University, Chicago,

IL 60613, USA.

Institute of Psychiatry,

London, UK.

A Screening Instrument for

Chronic Fatigue Syndrome

Reliability and Validity

Politics, science, and the

emergence of a new disease.

The case of chronic fatigue

syndrome.

Chronic fatigue syndrome:

relationships of self-ratings

and actigraphy.

Research with Children and

Adolescents with Chronic

Fatigue Syndrome

Methodologies, Designs, and

Special Considerations

The prognosis of chronic

fatigue and chronic fatigue

syndrome: a systematic

review.

Journal of Chronic Fatigue

Syndrome 1997: 3(1): 39 - 59

Am Psychol 1997

Sep;52(9):973-83Comment

in: Am Psychol. 1998

Sep;53(9):1080-2

Psychol Rep 1997 Dec;81(3

Pt 2):1223-6

Journal of Chronic Fatigue

Syndrome 1997: 3(2): 3 - 13

QJM 1997 Mar;90(3):223-33

comment in: QJM. 1997

Nov;90(11):723 QJM. 1997

Nov;90(11):723-5

found persistent parvovirus B19 viremia, which was detectable by polymerase chain reaction (PCR) despite

the presence of IgM and IgG antibodies to parvovirus B19. Testing of samples from this patient suggested

that in some low viremic states parvovirus B19 DNA is detectable by nested PCR in plasma but not in

serum. The patient's fever resolved with the administration of intravenous immunoglobulin.

Because estimates of the prevalence of Chronic Fatigue Syndrome (CFS) have been quite variable, there is

a need for a screening instrument and second stage medical assessment that will produce the most valid

estimate of the CFS prevalence. In the present study, four groups of 15 subjects each were recruited:

patients diagnosed with (1) CFS, (2) Lupus, (3) Multiple Sclerosis (MS), and (4) a healthy control group.

Participants were interviewed twice over a two week period of time with a screening instrument comprising

The Fatigue Scale and a newly configured section. The screening instrument had excellent test-retest and

interrater reliability. This screening instrument therefore has utility for CFS community-based

epidemiologic research. However, while the instrument differentiates with CFS from those who are healthy,

it is less likely to distinguish CFS from other autoimmune diseases (especially Lupus). Thus, future

community-based CFS prevalence studies should encompass both a screening and a medical examination to

adequately differentiate CFS from other illnesses with overlapping symptomatology. We recommend a twostage

research design with (1) a screening instrument with good sensitivity and (2) medical assessments of

CFS positives from stage 1 to deal with the specificity problem.

Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research

suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many

physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent

to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. By the mid-

1990s, findings from more representative epidemiological studies indicated considerably higher CFS

prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous

patient groups, possibly including some patients with pure psychiatric disorders. Social scientists have the

expertise to more precisely define this syndrome and to develop appropriate and sensitive research

strategies for understanding this disease.

Chronic Fatigue Syndrome is a baffling disease potentially affecting millions of Americans. Self-rating

scales were developed to assess this condition but have yet to be validated with objective measures of

activity. The present study of a 45-yr.-old man evaluated the relationships between scores on self-rating

scales used to measure Chronic Fatigue Syndrome and actigraphy. Measured activity was related to

predictors of fatigue but not to fatigue. The implications of these findings are discussed.

Chronic fatigue syndrome (CFS) in children and adolescents presents unique challenges and opportunities

to researchers. Issues specific to research conducted on children and adolescents with CFS are discussed.

Such issues include the importance of utilizing a consistent definition of CFS and ascertaining that all

participants meet the criteria, the need for attention to wading of questions regarding fatigue, and the

significance of medical evaluations as part of a research study. Considerations pertaining to research with

minors, such as confidentiality and assent, are explored. Finally, suggestions for future research on children

are made.

The prognosis of chronic fatigue syndrome and chronic fatigue has been studied in numerous small case

series. We performed a systematic review of all studies to determine the proportion of individuals with the

conditions who recovered at follow-up, the risk of developing alternative physical diagnoses, and the risk

factors for poor prognosis. A literature search of all published studies which included a follow-up of

patients with chronic fatigue syndrome or chronic fatigue were performed. Of 26 studies identified, four

studied fatigue in children, and found that 54-94% of children recovered over the periods of follow-up.

Another five studies operationally defined chronic fatigue syndrome in adults and found that < 10% of

subjects return to pre-morbid levels of functioning, and the majority remain significantly impaired. The

remaining studies used less stringent criteria to define their cohorts. Among patients in primary care with

fatigue lasting < 6 months, at least 40% of patients improved. As the definition becomes more stringent the

prognosis appears to worsen. Consistently reported risk factors for poor prognosis are older age, more

chronic illness, having a comorbid psychiatric disorder and holding a belief that the illness is due to

physical causes. Review, Multicase

Kane RL, Gantz NM, Department of Psychology, Neuropsychological and Neuropsychiatry Although patients with chronic fatigue syndrome (CFS) typically present subjective complaints of cognitive


ME Research UK — Database of Research Publications 1997

DiPino RK.

Kerr JR, Anne-Marie

Barrett , Martin D. Curran

, Wilhelmina M.H. Behan,

Derek Middleton, Peter O.

Behan

Knepper S.

Koehoorn J, Fechter MM,

de Vries H.

Kroneman H, Croon NH.

Kubo K, Fujiyoshi T,

Yokoyama MM, Kamei K,

Richt JA, Kitze B, Herzog

S, Takigawa M, Sonoda S.

Veterans Affairs Medical

Center, Baltimore, MD

21201, USA.

Department of

Neuropsychiatry, Faculty of

Medicine, Kagoshima

University, Japan.

psychological functioning in

chronic fatigue syndrome.

Brief Communications:

Parvovirus B19 and Chronic

Fatigue Syndrome

Ned Tijdschr Geneeskd.

1997 Aug 2;141(31):1510-2

[Chronic fatigue

syndrome].[article in Dutch]

[Chronic fatigue

syndrome].[article in Dutch]

[Chronic fatigue

syndrome].[article in Dutch]

Lack of association of Borna

disease virus and human T-

cell leukemia virus type 1

infections with psychiatric

disorders among Japanese

patients.

Neuropsychol Behav Neurol

1997 Jan;10(1):25-31

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 101 -

107

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2360

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1505-7

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2362-3

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1516-9

Ned Tijdschr Geneeskd 1997

Sep 13;141(37):1791

Clin Diagn Lab Immunol

1997 Mar;4(2):189-94

and psychological difficulties, studies to date have provided mixed objective support for the existence of

specific cognitive deficits. The present study was designed to examine differences in performance between

individuals diagnosed with CFS and matched controls with respect to sustained attention, processing

efficiency, learning, and memory. Subjects included 17 patients meeting Centers for Disease Control

research criteria for CFS and 17 control subjects. Subjects were administered six measures assessing

attention, memory, and word-finding ability and two measures assessing psychological distress. For the

most part, the two groups did not differ on measures of neurocognitive functioning. Significant group

differences were found on a single measure of attention and incidental memory. However, CFS patients

differed markedly from controls with respect to reported psychological distress. The results support

previous findings of notable levels of psychological distress among CFS patients. They also suggest the

need for alternative research paradigms to assess the cognitive abilities of CFS patients.

Objective. To investigate the skeletal muscle of patients with chronic fatigue syndrome (CFS) for

parvovirus B19. Methods. DNA was extracted from skeletal muscle biopsies from six patients with CFS

diagnosed according to thc criteria of the Centers for Disease Control and Prevention and six control cases.

Extracted DNA was checked for purity by agarose gel electrophoresis and examined for the presence of

B19 DNA by a nested polymerase chain reaction (PCR) method. Results. One of the six biopsies from the

CFS group and one of the six from the control group were positive for B19 DNA (Two-tailed P value = 1).

Nucleotide sequencing of the PCR product from the CFS patient revealed one silent mutation from A → G

at nucleotide 1530 when compared with the published sequence. Nucleotide sequencing of the PCR

product from the control patient with mild arthralgia revealed 10 mutations when compared with the

published sequence, all silent except the one at nt 1466 (G → C), which resulted in an amino acid change

from serine to threonine. Conclusion. The incidence of parvovirus B19 detected in muscle is not increased

in patients with CFS compared with controls and the virus in unlikely to play a role in the aetiology of this

disorder.

Borna disease virus (BDV) infection has been suspected to be a possible etiological factor in human

psychiatric disorders and recently in chronic fatigue syndrome. Evidence of the correlation of BDV

infection with these disorders remained unclear. Kagoshima is known to be one of the major areas in which

human T-cell leukemia virus type 1 (HTLV-1) is endemic; this is the first isolated human retrovirus that

causes adult T-cell leukemia with neurological symptoms. The present study aimed to clarify whether BDV

and HTLV-1 infections are associated with psychiatric disorders among Japanese patients. Subjects were

346 patients with psychiatric disorders (schizophrenia, 179; mood disorder, 123; and others, 44) and 70

healthy controls. Anti-BDV antibodies from plasma samples were screened by the indirect

immunofluorescence (IF) method using BDV-infected MDCK cells. Results revealed that only three

samples were found to be weakly positive for BDV in the IF assay and seronegative by Western blot

(immunoblot) assay. Furthermore, BDV-p24 related RNA in peripheral blood mononuclear cells from 106

of 346 psychiatric patients and 12 or 70 healthy controls by p24-reverse transcription PCR was examined.

Two mood disorder patients were positive for BDV-p24 RNA but seronegative. To detect anti-HTLV-1

antibodies the plasma samples were screened by the particle agglutination method and no significant

difference in seropositivity for anti-HTLV-1 antibody was found between the patients and healthy controls.

These results also suggested that there is a lack of association between BDV and HTLV-1 infections with


ME Research UK — Database of Research Publications 1997

Lakein DA, Fantie BD,

Grafman J, Ross S,

O'Fallon A, Dale J, Straus

SE.

Lapp CW, Hyman HL.

Lapp CW.

Lawrie SM, MacHale SM,

Power MJ, Goodwin GM.

Lawrie SM, Manders DN,

Geddes JR, Pelosi AJ.

Levine PH, Snow PG,

Ranum BA, Paul C, Holmes

MJ.

American University, USA.

Edinburgh University

Department of Psychiatry,

Royal Edinburgh Hospital.

Department of Medicine,

George Washington

University Medical Center,

Washington, DC, USA.

Patients with chronic fatigue

syndrome and accurate

feeling-of-knowing

judgments.

Diagnosis of chronic fatigue

syndrome.

Exercise limits in chronic

fatigue syndrome.

Is the chronic fatigue

syndrome best understood as

a primary disturbance of the

sense of effort

A population-based

incidence study of chronic

fatigue.

Epidemic neuromyasthenia

and chronic fatigue syndrome

in west Otago, New Zealand.

A 10-year follow-up.

J Clin Psychol 1997

Nov;53(7):635-45

Arch Intern Med 1997 Dec 8-

22;157(22):2663-4 Comment

on: Arch Intern Med. 1997

Mar 10;157(5):491-2

Am J Med 1997

Jul;103(1):83-4 Comment

on: Am J Med. 1996

Jun;100(6):634-40

Psychol Med 1997

Sep;27(5):995-9

Psychol Med 1997

Mar;27(2):343-53

Arch Intern Med 1997 Apr

14;157(7):750-4

psychiatric disorders among Japanese patients.

Many Chronic Fatigue Syndrome (CFS) patients complain of memory impairments which have been

difficult to document empirically. Subjective complaints of memory impairment may be due to a deficit in

metamemory judgment. CFS patients and matched controls were tested with a computerized Trivia

Information Quiz that required them to rate their confidence about correctly recognizing an answer in a

multiple choice format that they had been unable to remember in a fact-recall format. Even though CFS

patients reported significantly greater amounts of fatigue, cognitive, and physical symptoms, the accuracy

of their confidence levels and recognition responses were similar to controls. This finding suggests that a

metamemory deficit is not the cause of the memory problems reported by CFS patients.

BACKGROUND: Most research on syndromes of chronic fatigue has been conducted in clinical settings

and is therefore subject to selection biases. We report a population-based incidence study of chronic fatigue

(CF) and chronic fatigue syndrome (CFS). METHODS: Questionnaires assessing fatigue and emotional

morbidity were sent to 695 adult men and women who had replied to a postal questionnaire survey 1 year

earlier. Possible CFS cases, subjects with probable psychiatric disorder and normal controls were

interviewed. RESULTS: Baseline fatigue score, the level of emotional morbidity and a physical attribution

for fatigue were risk factors for developing CF. However, after adjusting for confounding, premorbid

fatigue score was the only significant predictor. A minority of CF subjects, all female, had consulted their

general practitioner; higher levels of both fatigue and emotional morbidity were associated with

consultation. Possible CFS cases reported similar rates of current and past psychiatric disorder to

psychiatric controls, but after controlling for fatigue or a diagnosis of neurasthenia the current rates were

more similar to those of normal controls. Two new cases of CFS were confirmed. CONCLUSIONS: Both

fatigue and emotional morbidity are integral components of chronic fatigue syndromes. The demographic

and psychiatric associations of CFS in clinical studies are at least partly determined by selection biases.

Given that triggering and perpetuating factors may differ in CFS, studies that examine the similarities and

differences between chronic fatigue syndromes and psychiatric disorder should consider both the stage of

the illness and the research setting.

BACKGROUND: In 1984, an outbreak of an illness characterized by prolonged unexplained fatigue was

reported in West Otago, New Zealand. This outbreak resembled other reported outbreaks of epidemic

neuromyasthenia in that affected individuals presented with a spectrum of complaints ranging from

transient diarrhea and upper respiratory disorders to chronic fatigue syndrome (CFS). OBJECTIVE: To

obtain a perspective on the natural history of CFS not possible in clinic-based studies. METHODS:

Twenty-three of the 28 patients in the original report were contacted and asked to complete written

questionnaires. Interviews were obtained in person or via telephone. RESULTS: Ten (48%) of the 21

patients with satisfactory interviews appeared to meet the current Centers for Disease Control and

Prevention (CDC) case definition of CFS, and 11 were classified as having prolonged or idiopathic fatigue.

A return to premorbid activity was seen in most (n = 16) patients, although some reported the need to

modify their lifestyle to prevent relapses. A female predominance was noted in those meeting the CDC case

definition for CFS, whereas males predominated in patients diagnosed as having prolonged or idiopathic

fatigue. CONCLUSIONS: The high proportion of patients recovering from CFS in the West Otago cluster

suggests that epidemic-associated CFS has a better prognosis than sporadic cases. Female sex was


ME Research UK — Database of Research Publications 1997

Levine PH.

Lodi R, Taylor DJ, Radda

GK.

Make B, James F. Jones

MD

Malt UF, Nerdrum P,

Oppedal B, Gundersen R,

Holte M, Lone J.

Manu P

Department of Medicine,

George Washington

University Medical Center,

Washington, D.C. 20037,

USA.

Department of

Psychosomatic and

Behavioural Medicine,

National Hospital, Oslo,

Norway.

Epidemiologic advances in

chronic fatigue syndrome.

Chronic fatigue syndrome

and skeletal muscle

mitochondrial function.

Impairment of Patients with

Chronic Fatigue Syndrome

Physical and mental

problems attributed to dental

amalgam fillings: a

descriptive study of 99 selfreferred

patients compared

with 272 controls.

Disablility EvaluationLong-

Term Disability for Chronic

Fatigue Syndrome

J Psychiatr Res 1997 Jan-

Feb;31(1):7-18

Muscle Nerve 1997

Jun;20(6):765-6 Comment

on: Muscle Nerve. 1996

May;19(5):621-5

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 43 - 55

Psychosom Med 1997 Jan-

Feb;59(1):32-41

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 19 - 30

confirmed as an important risk factor for CFS.

Epidemiologic studies of chronic fatigue syndrome (CFS) have been hampered by the absence of a specific

diagnostic test, but with increasing interest in this disorder there has been a greater understanding of the

risk factors, illness patterns, and other aspects of this multisystem disorder. Working case definitions have

been developed for research purposes but they have continued to change over time and have not always

been utilized precisely by various investigators. This has been a major factor in the widely varying

estimates of prevalence rates, but two different studies using the same working definition and including a

medical work-up have estimated the prevalence to be approximately 200/100,000. Clusters of CFS cases,

which appear to be related to earlier reports of "epidemic neuromyasthenia", have attracted considerable

attention and appear to be well documented, although investigated with varying methodology and often

with dissimilar case definitions. Risk factors for cases occurring in clusters and sporadically appear to be

similar, the most consistent ones being female gender and the co-existence of some form of stress, either

physical or psychological. The prognosis of CFS is difficult to predict, although cases occurring as part of

clusters appear to have a better prognosis as a group than sporadic cases, and those with an acute onset

have a better prognosis than those with gradual onset. It is highly unlikely that there is a single agent,

infectious or noninfectious, that is responsible for more than a small proportion of CFS cases and, at the

present time, the risk factors for developing CFS appear to lie more prominently in the host rather than the

environment.

OBJECTIVE: The physical and mental symptomatology of 99 self-referred patients complaining of

multiple somatic and mental symptoms attributed to dental amalgam fillings were compared with patients

with known chronic medical disorders seen in alternative (N = 93) and ordinary (N = 99) medical family

practices and patients with dental amalgam fillings (N = 80) seen in an ordinary dental practice. METHOD:

The assessments included written self-reports, a 131-item somatic symptom checklist; Eysenck Personality

Questionnaire, the General Health Questionnaire, and Toronto Alexithymia Scale. RESULTS: The dental

amalgam sample reported significantly more physical symptoms from all body regions. Self-reports

suggested that 62% suffered from a chronic anxiety disorder (generalized anxiety disorder or panic). Fortyseven

percent suffered from a major depression compared with 14% in the two clinical-comparison samples

and none in the dental control sample. Symptoms suggesting somatization disorder were found in 29% of

the dental amalgam sample compared with only one subject in the 272 comparison subjects. One third of

the dental amalgam patients reported symptoms of chronic fatigue syndrome compared with none in the

dental control sample and only 2 and 6%, respectively, in the two clinical comparison samples. The dental

amalgam group reported higher mean neuroticism and lower lie scores than the comparison groups.

CONCLUSION: Self-referred patients with health complaints attributed to dental amalgam are a

heterogeneous group of patients who suffer multiple symptoms and frequently have mental disorders. There

is a striking similarity with the multiple chemical sensitivity syndrome.

To determine the quality of medical evaluations leading to long-term disability payments for chronic

fatigue syndrome (CFS) we conducted a structured cross-sectional study of 76 patients receiving such

benefits for an average of 2.1 years. Most of the subjects were middle-aged, white (99%), women (87%)

who had been previously employed in "white-collar" jobs (96%). In all cases the claim of disability was

based on subjective reports of substantial impairment in exercise tolerance and cognitive ability. The

quality of disability determinations was judged by the fulfillment of four requirements: correct CFS

diagnosis, psychiatric evaluation, neuropsychological testing and physical capacity measurement. The

analysis indicated that none of the claims had been fully evaluated and that in 34% of cases none of the

requirements had been fulfilled. The diagnosis of CFS was incorrect in 38% of cases. The majority of

claimants (84%) had active psychiatric disorders, but only 32% had been evaluated by psychiatrists. Only

14% of claimants had their physical capacity objectively assessed and only 11% had formal testing of their


ME Research UK — Database of Research Publications 1997

Manu P

Marcovitch H.

Marshall PS, Forstot M,

Callies A, Peterson PK,

Schenck CH.

Martin WJ.

Mawle AC, Nisenbaum R,

Dobbins JG, Gary HE Jr,

Stewart JA, Reyes M,

Steele L, Schmid DS,

Reeves WC.

Mawle AC.

Department of Psychiatry,

Hennepin County Medical

Center, Minneapolis, MN

55415, USA.

Center for Complex

Infectious Diseases,

Rosemead, Calif. 91770,

USA. wjmartin@bcf.usc.edu

Division of Viral and

Rickettsial Diseases, Centers

for Disease Control and

Prevention, Atlanta, Georgia

30333, USA.

Division of Viral and

Rickettsial Diseases, Centers

for Disease Control and

Prevention, Atlanta, Georgia

30333, USA.

Disability Evaluation for

Chronic Fatigue Syndrome

Managing chronic fatigue

syndrome in children.

Cognitive slowing and

working memory difficulties

in chronic fatigue syndrome.

Detection of RNA sequences

in cultures of a stealth virus

isolated from the

cerebrospinal fluid of a

health care worker with

chronic fatigue syndrome.

Case report.

Immune responses associated

with chronic fatigue

syndrome: a case-control

study.

Chronic fatigue syndrome.

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 9 - 17

BMJ 1997 Jun

7;314(7095):1635-

6Comment in: BMJ. 1997

Oct 11;315(7113):947;

discussion 948 BMJ. 1997

Oct 11;315(7113):949

Comment on: BMJ. 1997 Jun

7;314(7095):1647-52

Psychosom Med 1997 Jan-

Feb;59(1):58-66 comment in:

Psychosom Med. 1997 Nov-

Dec;59(6):638

Pathobiology 1997;65(1):57-

60

J Infect Dis 1997

Jan;175(1):136-41

Immunol Invest 1997 Jan-

Feb;26(1-2):269-73

cognitive abilities. The data suggest that most medical evaluations resulting in disability payments for CFS

are flawed as a result of the overdiagnosis of CFS, the insufficient attention given the comorbid psychiatric

disorders, and the infrequent objective testing of physical capacity and cognitive function.

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) commonly report problems with attention,

memory, learning, and speed of cognitive processing. This study attempted to evaluate these complaints

using objective test criteria. METHOD: A test battery composed of six tests assessing these cognitive

functions was given on two consecutive days. Twenty CFS patients were compared with 20 healthy control

subjects and 14 patients with a history of major depression or dysthymia matched by age, intelligence,

education level, and sex. RESULTS: Compared with control subjects, CFS patients consistently scored

lower on tests in which motor and cognitive processing speeds were a critical factor, eg, reaction-time

tasks. They also had more difficulty on working-memory tests in which rapid cognitive processing speed is

also an important factor. The effort made on the first day of testing did not result in a decline in cognitive

function on the following day. CFS patients did not qualify as having affective disorder by several different

diagnostic criteria. Nonetheless, CFS patients' test performances did not differ from patients with a history

of major depression or dysthymia. CONCLUSIONS: It is concluded that, although CFS and major

depression and dysthymia have distinct clinical features, these disorders have slowed motor and cognitive

processing speed in common.

A cytopathic stealth virus was cultured from the cerebrospinal fluid of a nurse with chronic fatigue

syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the patient's culture

yielded positive results with primer sets based on sequences of a previously isolated African green monkey

simian-cytomegalovirus-derived stealth virus. The same primer sets did not yield PCR products when tested

directly on DNA extracted from the cultures. The findings lend support to the possibility of replicative

RNA forms of certain stealth viruses and have important implications concerning the choice of therapy in

this type of patient.

An exploratory case-control study was conducted to assess whether the many reported differences in the

immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of

CFS. Although many studies have reported differences between cases and controls in various measures of

immune function, none of these differences were found in all studies. In this study, no differences were

found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels;

delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to

mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface

markers in the total CFS population. However, when the patients were subgrouped by type of disease onset

(gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences

were seen.

Chronic fatigue syndrome (CFS) has emerged as a public health concern over the past decade. A working

case definition was created in 1988 and revised in 1994, and this has been used to establish prevalence

estimates using physician-based surveillance and an a random digit dial telephone survey. Although CFS

has some characteristics of an infectious disease, so far no infectious agent has been associated with the

illness. Studies of immune function in CFS patients failed to detect differences between cases and healthy

controls. However, when cases were subgrouped according to whether they had a sudden or gradual onset,

differences in immunologic markers were detected between cases and their matched controls.

McGregor NR, R. H. A Preliminary Assessment of Journal of Chronic Fatigue A previous investigation of a cohort of 20 chronic fatigue syndrome (CFS) patients revealed an increased


ME Research UK — Database of Research Publications 1997

Dunstan, H. L. Butt , T. K.

Roberts , I. J. Klineberg ,

M. Zerbes

Miro O, Font C,

Fernandez-Sola J,

Casademont J, Pedrol E,

Grau JM, Urbano-

Marquez A.

Moorkens G, Manuel y

Keenoy B, Vertommen J,

Meludu S, Noe M, De

Leeuw I.

Morriss RK, Wearden AJ,

Battersby L.

Servicio de Medicina Interna,

Hospital Clinic i Provincial,

Universidad de Barcelona.

Department of Internal

Medicine, University

Hospital, Antwerp, Belgium.

University of Manchester,

Department of Community

Psychiatry, UK.

the Association of SCL-90-R

Psychological Inventory

Responses with Changes in

Urinary Metabolites in

Patients with Chronic Fatigue

Syndrome

[Chronic fatigue syndrome:

study of the clinical course of

28 cases].[article in Spanish]

Magnesium deficit in a

sample of the Belgian

population presenting with

chronic fatigue.

The relation of sleep

difficulties to fatigue, mood

and disability in chronic

fatigue syndrome.

Syndrome 1997: 3(1): 17 - 37

Med Clin (Barc) 1997 Apr

19;108(15):561-5Comment

in: Med Clin (Barc). 1997

Apr 19;108(15):577-9

Magnes Res 1997

Dec;10(4):329-37

J Psychosom Res 1997

Jun;42(6):597-605

urinary excretion of an unusual metabolite, tentatively identified as amino-hydroxyN-methyl-pyrrolidine

(coded CFSUMl) and ß-alanine, compared with 45 control subjects. The relative abundances of both

CFSUM1 and ß-alanine were positively associated with the core diagnostic symptoms of CFS and

associated changes in amino and organic acid excretion. The psychological attributes of these CFS patients

and controls were assessed in this study by using the Symptom Check List-90-revised (SCL-90-R)

psychological inventory. The CFS patients had increases in the SCL-90-R somatization, obsessive

compulsive, depression, anxiety and phobic anxiety dimension scores. Nineteen of 20 CFS patients had

somatization T-scores ≥ 63 (P < 0.0001), suggestive of a somatization disorder. Multiple regression

analysis indicated that somatization was the most important SCL-90-R defined dimension discriminating

CFS from control subjects. Depression and anxiety were not found to be important inter-group

determinants. The dimension scores were each related to specific changes in the urinary excretion of

organic and amino acids, suggesting that each is biochemically distinct and has an organic basis. Cluster

analysis of dimension profiles revealed that the profile with increased prevalence (P < 0.0001) in CFS

patients was associated with increased excretion of CFSUM1 (P < 0.005) and had increases in

somatization, obsessive compulsion and depression dimension scores. The PSDI as a measure of SCL-90-R

symptom severity was positively correlated with CFSUM1 (model P < 0.003). CFSUM1 was also the

primary correlate for the somatization dimension (model P < 0.0008), but was not associated with any other

SCL-90-R-defined dimension. Another unidentified urinary metabolite, coded UM15, was the primary

correlate for depression (model P < 0.0004) and was associated with multiple dimension elevations by both

cluster and logistic regression analysis; the excretion of this compound was unrelated to CFSUM1. These

results indicated that, in this CFS cohort, the SCL-90-R defined psychological changes were strongly

associated with changes in the biochemical homeostasis of patients, suggestive of an organic basis to CFS.

BACKGROUND: Chronic fatigue syndrome (CFS) is an entity of unknown etiopathogenesis without

specific markers. The diagnosis is based on clinical criteria. There are few studies evaluating the natural

evolution and prognosis-related factors in CFS. OBJECTIVES: a) to evaluate the outcome of patients

suffering from CFS, and b) to detect predictive factors associated with a better prognosis. MATERIAL

AND METHODS: Clinical records of all patients diagnosed of CFS between January 1986 and December

1992 were retrospectively reviewed. Of these patients, we included those fulfilling the CDC criteria for

CFS, with a follow-up period greater than one year. We evaluated epidemiological, clinical and evolutive

data recorded by their usual physicians. Moreover, the patients were interviewed in order to know their own

appreciation with respect to their current clinical status, as well as their present working situation.

RESULTS: Twenty-eight patients were included in the present study. Their mean age was 38 +/- 7.

Seventy-five percent of them were women. The mean time of clinical follow-up was of 3.2 +/- 1.8 years.

According to evaluation, 21% of patients improved or became asymptomatic. A similar percentage (28%)

of improvement was obtained from the interview. Forty-eight percent of cases had transitory or definitive

laboral incapacity. Regarding to prognostic factors, we could not find any statistical differences among the

analyzed variables except for marital status. In this variable, married patients had better outcome than

unmarried patients. CONCLUSION: CFS is an entity with a poor outcome, since it evolves towards to

chronicity in an important number of cases. In addition, strong functional disability may be present, leading

frequently to laboral incapacity. Review, Multicase

97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38 years) with complaints of

chronic fatigue (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) have been enrolled in a

prospective study to evaluate the Mg status and the dietary intake of Mg. An IV loading test (performed

following the Ryzen protocol) showed a Mg deficit in 44 patients. After Mg supplementation in 24 patients,

the loading test showed a significant decrease (p = 0.0018) in Mg retention. Mean values of serum Mg, red

blood cell Mg and magnesuria showed no significant difference between patients with or without Mg

deficiency. No association was found between Mg deficiency, CFS or FM. However serum Mg level was

significantly lower in the patients with spasmophilia than in the other patients.

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic

fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38

psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were

matched for age and gender. There were few differences between the prevalence or nature of sleep


ME Research UK — Database of Research Publications 1997

Mounstephen A, Sharpe M.

Nakaya T, Kuratsune H,

Kitani T, Ikuta K.

Nishikai M, Kosaka S.

Owens PE, O'Brien ET.

Patarca R

University of Edinburgh,

Royal Edinburgh Hospital,

UK.

Section of Serology,

Hokkaido University.

Blood Pressure Unit,

Beaumont Hospital, Dublin,

Republic of Ireland.

Chronic fatigue syndrome

and occupational health.

[Demonstration on Borna

disease virus in patients with

chronic fatigue

syndrome].[article in

Japanese]

Incidence of antinuclear

antibodies in Japanese

patients with chronic fatigue

syndrome.

Hypotension: a forgotten

illness.

Report of the International

Meeting on Standardization

and Calibration of Cytokine

Immunoassays A User's

Perspective

Occup Med (Lond) 1997

May;47(4):217-27

Nippon Rinsho 1997

Nov;55(11):3064-71

Arthritis Rheum 1997

Nov;40(11):2095-7

Comment on: Arthritis

Rheum. 1997 Feb;40(2):295-

305

Blood Press Monit 1997

Dec;2(1):3-14

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 97 - 99

complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder.

CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in

maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients.

Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong

association between relapse and sleep disturbance. Certain types of sleep disorder were associated with

increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS.

For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to

the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS. Randomized

Controlled Trial

Chronic fatigue syndrome (CFS) is a controversial condition that many occupational physicians find

difficult to advise on. In this article we review the nature and definition of CFS, the principal aetiologic

hypotheses and the evidence concerning prognosis. We also outline a practical approach to patient

assessment, diagnosis and management. The conclusions of this review are then applied to the disability

discrimination field. The implications of the new UK occupational health legislation are also examined.

Despite continuing controversy about the status, aetiology and optimum management of CFS, we argue that

much can be done to improve the outcome for patients with this condition. The most urgent needs are for

improved education and rehabilitation, especially in regard to employment. Occupational physicians are

well placed to play an important and unique role in meeting these needs.

Chronic fatigue syndrome (CFS), a recently named heterogeneous disorder, is an illness of unknown

etiology. The association between CFS and several viral infection has been suggested. Here, we centered on

the possible link between CFS and Borna disease virus (BDV) infection. BDV is a neurotropic,

nonsegmented negative-strand (NNS) RNA virus. Recent epidemiological data have suggested that BDV

may be closely associated with depression and schizophrenia in humans. In Japanese patients with CFS, the

prevalence of BDV infection was 34% (30/89) and 12% (7/57) by immunoblotting and PCR analysis,

respectively. Furthermore, anti-BDV antibodies and BDV RNA were detected in a family cluster with CFS.

These results suggested that this virus contributes to or initiates CFS, although the single etiologic role of

BDV is unlikely. Review Literature

Low blood pressure is a frequently encountered phenomenon in clinical practice. Few practitioners in the

Western world however regard chronic low blood pressure as a genuinely pathological disease state.

Evidence is emerging that chronic hypotension is associated with considerable morbidity in the community.

It has recently been implicated as the causative mechanism in patients with the chronic fatigue syndrome.

Identification of low blood pressure can prove probjlematic, so ambulatory blood pressure monitoring may

prove a more reliable method both for determining mean blood pressure levels and for identifying episodes

of marked hypotension. Low blood pressure is broadly divided into two categories, chronic constitutional

hypotension and hypotension associated with abnormal postural control. The causes are examined and the

clinical presentations are discussed. An approach to investigation and diagnosis is outlined, and current

options regarding treatment and management are described. The clinical spectrum of low blood pressure is

wide. From young patients with vagally mediated syncope or patients with iatrogenic hypotension to elderly

patients with autonomic degenerative conditions, there exists a substantial body of patients with potentially

avoidable or treatable morbidity. Such a group requires more rigorous scientific investigation and a more

sympathetic clinical approach.

Peakman M, Deale A, Field Department of Immunology, Clinical improvement in Clin Immunol Immunopathol The relationship between markers of immune function and chronic fatigue syndrome (CFS) is controversial.


ME Research UK — Database of Research Publications 1997

R, Mahalingam M, Wessely

S.

Pearn JH.

Peterson DL

Plioplys AV, Plioplys S,

Davis JS 4th.

Plioplys AV, Plioplys S.

Plioplys AV.

Plioplys AV.

King's College School of

Medicine & Dentistry,

London, United Kingdom.

Department of Paediatrics

and Child Health, Royal

Children's Hospital,

Brisbane, QLD.

Department of Neurology,

University of Illinois College

of Medicine at Chicago,

USA.

Chronic Fatigue Syndrome

Center, Department of

Research, Mercy Hospital

Chicago, Ill 60616, USA.

Chronic Fatigue Syndrome

Center, Mercy Hospital,

Chicago, IL, USA.

Chronic Fatigue Syndrome

Research Center, Mercy

Hospital and Medical Center,

Chicago, IL 60616, USA.

chronic fatigue syndrome is

not associated with

lymphocyte subsets of

function or activation.

Chronic fatigue syndrome:

chronic ciguatera poisoning

as a differential diagnosis.

EditorialsChronic Fatigue

Syndrome and Disability

Meeting the frustrations of

chronic fatigue syndrome.

Amantadine and L-carnitine

treatment of Chronic Fatigue

Syndrome.

Antimuscle and anti-CNS

circulating antibodies in

chronic fatigue syndrome.

Chronic fatigue syndrome

should not be diagnosed in

children.

1997 Jan;82(1):83-91 To examine the relationship directly, 43 subjects with CFS entering a randomized controlled trial of a

nonpharmacological treatment for CFS gave samples for immunological analysis before and after treatment.

Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated subsets did not differ

between CFS subjects and controls. Naive (CD45RA+ RO-) and memory (CD45RA- RO+) T cells did not

differ between subjects and controls. Natural killer cells (CD16+/CD56+/CD3-) were significantly

increased in CFS patients compared to controls, as was the percentage of CD11b+ CD8 cells. There were

no correlations between any immune variable and measures of clinical status, with the exception of a weak

correlation between total CD4 T cells and fatigue. There was a positive correlation between memory CD4

and CD8 T cells and depression scores and a negative correlation between naive CD4 T cells and

depression. No immune measures changed during the course of the study, and there was no link between

clinical improvement as a result of the treatment program and immune status. Immune measures did not

predict response or lack of response to treatment. In conclusion, we have been unable to replicate previous

findings of immune activation in CFS and unable to find any important associations between clinical

status, treatment response, and immunological status. Randomized Controlled Trial

Med J Aust 1997 Mar

17;166(6):309-10

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 5 - 7

Hosp Pract (Off Ed) 1997

Jun 15;32(6):147-50, 153-6,

160-1, passim

Neuropsychobiology

1997;35(1):16-23

Neurology 1997

Jun;48(6):1717-9

Pediatrics 1997 Aug;100(2 Pt

1):270-1

Patients face long-term disability, a variable prognosis, and too often, skeptical or misinformed doctors.

Physicians lack laboratory markers or definitive treatment. Nevertheless, the diagnosis can be made with

confidence by applying established diagnostic criteria- and selected laboratory studies to exclude other

disorders-while symptomatic medication can provide support until recovery begins.

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may

contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations

have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in

treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most

effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it

may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and

amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover

design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week

washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine.

Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment,

the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks

of treatment, there was no statistically significant difference in any of the clinical parameters that were

followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18

studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration.

The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was

unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated

medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and

laboratory correlates of CFS symptomatology and improvement parameters. Randomized Controlled Trial

Chronic fatigue syndrome (CFS) patients suffer from disabling physical and mental fatigue. Circulating

autoimmune antibodies may produce symptoms of muscular fatigue by reacting with acetylcholine

receptors or calcium binding channels. They can also produce mental status changes by reacting with

central nervous system (CNS) antigens. We thoroughly investigated the presence of circulating antimuscle

and anti-CNS antibodies in 10 CFS patients and 10 controls. We were unable to detect any pathogenic

antibodies.


ME Research UK — Database of Research Publications 1997

Pourmand R.

Ray C, Jefferies S, Weir

WR.

Redmond G.

Regland B, Andersson M,

Abrahamsson L, Bagby J,

Dyrehag LE, Gottfries CG.

Department of Neurology,

Indiana University School of

Medicine, Indianapolis,

USA.

Department of Human

Sciences, Brunel University,

Uxbridge, Middlesex, UK.

Women's Hormone Center

Beachwood, Ohio, USA.

Institute of Clinical

Neuroscience, Goteborg

University, Sweden.

Myasthenia gravis.

Coping and other predictors

of outcome in chronic fatigue

syndrome: a 1-year followup.

Mood disorders in the female

patient.

Increased concentrations of

homocysteine in the

cerebrospinal fluid in

patients with fibromyalgia

and chronic fatigue

syndrome.

Dis Mon 1997 Feb;43(2):65-

109

J Psychosom Res 1997

Oct;43(4):405-15

Int J Fertil Womens Med

1997 Mar-Apr;42(2):67-72

Scand J Rheumatol

1997;26(4):301-7

Adult-onset myasthenia gravis is an acquired autoimmune disorder of neuromuscular transmission in which

acetylcholine receptor antibodies attack the postsynaptic membrane of the neuromuscular junction.

Although the cause of this disease is unknown, the role of immune responses in its pathogenesis is well

established. Circulating acetylcholine receptor antibodies are present in 80% to 90% of patients with the

generalized form of myasthenia gravis. Most patients have ptosis, diplopia, dysarthria and dysphagia. The

weakness and fatigue worsen on exertion and improve with rest. Respiratory muscle and limb weakness are

rare at the onset of the disease. For the past two decades, there has been considerable progress in

understanding the diagnosis and management of myasthenia gravis. The diagnosis is based on clinical

presentation, neurologic examination, and confirmation by means of electrophysiologic testing and

immunologic studies. Myasthenia gravis mimics many neuromuscular diseases and even illnesses such as

depression and chronic fatigue syndrome. One should always exclude drug-induced myasthenia gravis for

all patients. With the introduction of new modalities of treatment, particularly immunosuppressive or

immunomodulating drugs, plasma exchange and thymectomy, the morbidity and mortality of myasthenia

gravis have decreased dramatically to the point that myasthenia gravis should not be considered as serious a

disease as it once was. Although the several therapeutic options are usually effective and have meant

independence in daily life to many patients with myasthenia gravis, well-designed, controlled, prospective

studies are still lacking.

In this prospective study, 137 patients with chronic fatigue syndrome were followed-up at a 1-year interval

to determine factors relating to outcomes. Nearly two thirds reported an improvement on direct ratings of

change. In analyses with fatigue and functional impairment at follow-up as the criteria, and controlling for

earlier status, poorer outcomes were predicted by illness duration, subjective cognitive difficulty, and

somatic symptoms; there was no influence of anxiety, depression, or general emotional distress. Fatigue

was also predicted by information-seeking, and impairment by behavioral disengagement and a low internal

locus of control. The belief that one's actions can influence outcomes modified the relationship between

illness accommodation and both fatigue and impairment; adverse outcomes were associated with

accommodating to illness only in the context of lower levels of perceived control. Thus, it is suggested that

interventions that either discourage avoidance of activity or enhance perceived control could benefit the

course of the illness.

Disruptive changes in mood and low energy level are among the most common reasons women consult a

physician. Usually no clear physiological explantation for these changes can be found. Many physicians

feel uncomfortable dealing with patients with these complaints. The purpose of this paper is to discuss a

practical approach to helping women with such conditions. A variety of terms have been utilized to refer to

the situation in which a female patient has decreased energy or labile mood. Premenstrual Syndrome (PMS)

and chronic fatigue syndrome (CFS) are currently popular terms. An association of low mood with

menstrual cycle phase is undoubted, with the late luteal-early premenstrual phase most commonly

associated with depression and irritability. It seems likely that women with PMS and those without it do not

differ in circulating hormone levels during their cycles but rather in the brain response to these. Estrogen

and progesterone receptors exist in the brain and change during the cycle. Elaborate diagnostic efforts are

rarely rewarding in managing mood and energy disorders. Of more value is a careful history particularly

concerned with the pattern of mood changes and with life stresses, accompanied by a thorough physical

examination and laboratory tests. In most cases, changes in mood and energy are a variant of clinical

depression. Changes in energy and sleep may be more evident than low affect. Treatment with an

appropriate antidepressant, usually a selective serotonin re-uptake inhibitor (SSRI), benefits most of these

patients. Allowing the patient to express concerns about stressful life situations is often of great value.

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue

syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15).

These items were chosen to constitute a proper neurasthenic subscale. Blood laboratory levels were

generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels

were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-

HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of

fatiguability and with CPRS-15. The correlations between vitamin B12 and clinical variables of the CPRSscale

in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency


ME Research UK — Database of Research Publications 1997

Richmond C.

Robbins JM, Kirmayer LJ,

Hemami S.

Rosenfeld WD, Walco GA.

Rowe KS.

Sadler M.

Salit IE.

Sandhaus SH

Department of Pediatrics,

University of Arkansas for

Medical Sciences, Arkansas

Children's Hospital, Little

Rock 72202, USA.

Adolescent/Young Adult

Center for Health,

Morristown Memorial

Hospital, 100 Madison

Avenue, Morristown, NJ

07962, USA.

Department of Paediatrics,

University of Melbourne

Royal Children's Hospital,

Victoria, Australia.

Division of Infectious

Diseases, Toronto Hospital,

Ontario, Canada.

irving.salit@utoronto.ca

Mad cows and Englishmen:

the aftermath of a BSE scare.

Latent variable models of

functional somatic distress.

One Test Too Many: Toward

an Integrated Approach to

Psychosomatic Disorders.

Double-blind randomized

controlled trial to assess the

efficacy of intravenous

gammaglobulin for the

management of chronic

fatigue syndrome in

adolescents.

Graded exercise in chronic

fatigue syndrome. Patients

were selected group.

Precipitating factors for the

chronic fatigue syndrome.

A Primer for Chronic Fatigue

Syndrome Claimants in

CMAJ 1997 Apr

1;156(7):1043-4

J Nerv Ment Dis 1997

Oct;185(10):606-15

Adolesc Med 1997

Oct;8(3):483-487

J Psychiatr Res 1997 Jan-

Feb;31(1):133-47

BMJ 1997 Oct

11;315(7113):947-8

Comment on: BMJ. 1997 Jun

7;314(7095):1647-52

728: J Psychiatr Res 1997

Jan-Feb;31(1):59-65

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 69 - 73

causes a deficient remethylation of HCY and is therefore probably contributing to the increased

homocysteine levels found in our patient group. We conclude that increased homocysteine levels in the

central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue

syndrome.

The consumption of prime beef cuts is down, animals have been slaughtered by the thousand and 3 farmers

have committed suicide as the mad-cow issue continues to cause concern in the United Kingdom. In this

report from London, Caroline Richmond also notes that the royal colleges have published a report stating

that chronic fatigue syndrome is a real illness and patients need help.

Latent variable models of functional somatic symptoms were estimated for a sample of 686 family

medicine patients. Symptom items from the NIMH Diagnostic Interview Schedule were selected to

approximate diagnoses of fibromyalgia syndrome (FMS), chronic fatigue syndrome (CFS), and irritable

bowel syndrome (IBS). Confirmatory factor analysis demonstrated that hypothesized latent variables of

somatic depression, somatic anxiety, FM-like, CF-like, and IB-like syndromes fit the observed covariations

better than models hypothesizing fewer latent variables. Results offer tentative confirmation of functional

somatic syndromes as discrete entities and suggest that relaxing the diagnostic criteria for somatization may

identify individuals with distress limited to a single functional system.

Conditions such as chronic fatigue syndrome (CFS), fibromyalgia, and several others belong to the group of

disorders in which both physiologic and psychologic factors are substantially involved, and in some cases

there may be no real distinction between the two. However, primary patient assessment usually employs an

array of clinical tools, and only after known physiologic factors are excluded is the patient referred for

psychologic or psychiatric evaluation. This chapter suggests that clinical evaluation should initially include

both physiologic and psychosocial assessment, which would minimize the division and greatly improve the

efficacy of the treatment.

A double blind randomized controlled trial was conducted in 71 adolescents aged 11-18 years. Inclusion in

the trial required fulfilment of the diagnostic criteria, (Fukuda et al., 1994). Three infusions of 1 gm/kg

(max 1 litre of 6 gm/100 ml in 10% w/v maltose solution) were given one month apart. The dummy

solution was a 10% w/v maltose solution with 1% albumin of equivalent volume for weight. Efficacy was

assessed by difference in a mean functional score including school attendance, school work, social activity

and physical activity, between baseline, three months and six months after the final infusion. There was a

significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic

Fatigue Syndrome of average duration 18 months. There was also a significant improvement for both

groups from the beginning of the trial to the six month post infusion follow-up. Adverse effects were

common with both solutions but not predictive of response. Neither solution could be identified by

recipients. Randomized Controlled Trial

The etiology of the Chronic Fatigue Syndrome (CFS) is unknown but it is usually considered to be

postinfectious or postviral. Many infecting agents have been suspected as causative but none has been

proven. We investigated precipitating factors in 134 CFS patients through the use of a questionnaire,

interview, clinical examination and serology for infecting agents; 35 healthy controls completed a similar

questionnaire. CFS started with an apparently infectious illness in 96 (72%) but a definite infection was

only found in seven of these 96 (7%). Thirty-eight (28%) had no apparent infectious onset: 15/38 (40%)

had noninfectious precipitants (trauma, allergy, surgery). There was no apparent precipitating event in

23/38 (61%). Immunization was not a significant precipitant. Stressful events were very common in the

year preceding the onset of CFS (114/134, 85%) but these occurred in only 2/35 (6%) of the controls (p <

.0001). The onset of CFS may be associated with preceding stressful events and multiple other precipitants.

An infectious illness is not uniformly present at the onset and no single infectious agent has been found;

CFS is most likely multifactorial in origin.


ME Research UK — Database of Research Publications 1997

Sargent CA, Stuart

Anderson, Michael Budek

See DM, Broumand N, Sahl

L, Tilles JG.

Sendrowski DP, Buker EA,

Gee SS.

Sharpe M, Chalder T,

Palmer I, Wessely S.

Department of Medicine,

U.C. Irvine Medical Center,

Orange 92668, USA.

Southern California College

of Optometry, Fullerton,

USA.

University of Edinburgh,

UK.

Applying for Long-Term

Disability Policy Benefits

Psychomotor Functioning in

Chronic Fatigue Syndrome

In vitro effects of echinacea

and ginseng on natural killer

and antibody-dependent cell

cytotoxicity in healthy

subjects and chronic fatigue

syndrome or acquired

immunodeficiency syndrome

patients.

An investigation of

sympathetic hypersensitivity

in chronic fatigue syndrome.

Chronic fatigue syndrome. A

practical guide to assessment

and management.

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 53 - 68

Immunopharmacology 1997

Jan;35(3):229-35

Optom Vis Sci 1997

Aug;74(8):660-3

Gen Hosp Psychiatry 1997

May;19(3):185-99

Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular

immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients

with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a

Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each

extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity

(ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or

= 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the

addition of either herb significantly increased ADCC of PBMC from all subject groups. Thus, extracts of

Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal

individuals and patients with depressed cellular immunity.

BACKGROUND: There are many theories, but the etiology of chronic fatigue syndrome (CFS) remains

unknown. Diagnosticians have set guidelines to try to classify the condition, but its clinical definition is

one of exclusion rather than defined by specific clinical testing. The primary goal of this investigation was

to find a diagnostic key to define CFS. CFS patients and those diagnosed with the sympathetic

hypersensitivity condition called fibromyalgia syndrome (FMS) exhibit identical brain single photon

emission computerized tomography (SPECT) images. Therefore, this investigation was initiated to see if

CFS patients also had denervation hypersensitivity of the sympathetic system. METHODS: A standardized

supersensitivity test was performed using an ocular instillation of two drops of 1.0% phenylephrine. Sixtytwo

subjects (29 CFS patients and 33 normals) participated in the study. Measurements of pupil size were

recorded by pupil gauge and flash photography. A pupillary dilation of greater than 2.5 mm would suggest

a sympathetic denervation hypersensitivity. RESULTS: For all participants, a small, but statistically

significant increase in pupil size was found (mean of 0.788 mm in normals and 0.931 mm in CFS patients).

The change in pupil size in the CFS patients and controls showed substantial overlap and was not

statistically significant (t = 0.83, p = 0.42, dF = 60). CONCLUSION: In conclusion, the results suggest that

a denervation hypersensitivity of the pupil does not occur in CFS patients. The use of 1.0% topical

phenylephrine had no diagnostic value in detecting CSF patients vs. normals.

Chronic fatigue and chronic fatigue syndrome (CFS) have become increasingly recognized as a common

clinical problem, yet one that physicians often find difficult to manage. In this review we suggest a

practical, pragmatic, evidence-based approach to the assessment and initial management of the patient

whose presentation suggests this diagnosis. The basic principles are simple and for each aspect of

management we point out both potential pitfalls and strategies to overcome them. The first, and most

important task is to develop mutual trust and collaboration. The second is to complete an adequate

assessment, the aim of which is either to make a diagnosis of CFS or to identify an alternative cause for the

patient's symptoms. The history is most important and should include a detailed account of the symptoms,

the associated disability, the choice of coping strategies, and importantly, the patient's own understanding

of his/her illness. The assessment of possible comorbid psychiatric disorders such as depression or anxiety

is mandatory. When the physician is satisfied that no alternative physical or psychiatric disorder can be

found to explain symptoms, we suggest that a firm and positive diagnosis of CFS be made. The treatment

of CFS requires that the patient is given a positive explanation of the cause of his symptoms, emphasizing

the distinction among factors that may have predisposed them to develop the illness (lifestyle, work stress,

personality), triggered the illness (viral infection, life events) and perpetuated the illness (cerebral

dysfunction, sleep disorder, depression, inconsistent activity, and misunderstanding of the illness and fear

of making it worse). Interventions are then aimed to overcoming these illness-perpetuating factors. The role

of antidepressants remains uncertain but may be tried on a pragmatic basis. Other medications should be

avoided. The only treatment strategies of proven efficacy are cognitive behavioral ones. The most important

starting point is to promote a consistent pattern of activity, rest, and sleep, followed by a gradual return to

normal activity; ongoing review of any 'catastrophic' misinterpretation of symptoms and the problem

solving of current life difficulties. We regard chronic fatigue syndrome as important not only because it


ME Research UK — Database of Research Publications 1997

Sharpe M, Hawton K,

Clements A, Cowen PJ.

Sharpe M.

Sharpley A, Clements A,

Hawton K, Sharpe M.

Shefer A, Dobbins JG,

Fukuda K, Steele L, Koo D,

Nisenbaum R, Rutherford

GW.

Shepherd C, Macintyre A.

University Department of

Psychiatry, Warneford and

Littlemore Hospitals, Oxford.

University of Edinburgh,

Royal Edinburgh Hospital,

United Kingdom.

Department of Psychiatry,

University of Oxford, United

Kingdom.

Epidemic Intelligence

Service Program, Centers for

Disease Control and

Prevention, Atlanta, GA

30333, USA.

Increased brain serotonin

function in men with chronic

fatigue syndrome.

Cognitive behavior therapy

for functional somatic

complaints. The example of

chronic fatigue syndrome.

Do patients with "pure"

chronic fatigue syndrome

(neurasthenia) have abnormal

sleep

Fatiguing illness among

employees in three large state

office buildings, California,

1993: was there an outbreak

Graded exercise in chronic

fatigue syndrome. Patients

BMJ 1997 Jul

19;315(7101):164-5

Psychosomatics 1997 Jul-

Aug;38(4):356-62

Psychosom Med 1997 Nov-

Dec;59(6):592-6

J Psychiatr Res 1997 Jan-

Feb;31(1):31-43

BMJ 1997 Oct

11;315(7113):947;

represents potentially treatable disability and suffering but also because it provides an example for the

positive management of medically unexplained illness in general.

Somatic complaints such as pain and fatigue that are unexplained by conventional disease are common in

medical practice and are referred to as functional, somatoform, or somatization symptoms. Despite frequent

chronicity, disability, and high associated medical costs, patients with these complaints are rarely offered

either constructive explanations or effective treatment. In this perspective, a cognitive-behavioral approach

to the problem is described, using chronic fatigue syndrome as an example. It is concluded that the utility of

the cognitive-behavioral theory and the proven effectiveness cognitive behavior therapy provide the basis

for a new evidence-based approach to psychosomatics.

OBJECTIVE: To determine whether patients with "pure" chronic fatigue syndrome (neurasthenia) have

sleep abnormalities which may contribute to subjective measures of daytime fatigue. METHOD: Sleep

characteristics of 20 patients meeting research criteria for chronic fatigue syndrome (CFS) but not

depression, anxiety, or sleep disorder were compared with sleep characteristics of 20 healthy subjects

matched for age and sex. Measures of sleep included a) subjective interview reports and sleep diaries and b)

home-based polysomnography. RESULTS: Patients with CFS complained of poor quality unrefreshing

sleep. They also napped during the day. Polysomnograph data showed no difference in actual nocturnal

sleep time between the two groups although patients with CFS spent significantly longer in bed (p < .01),

slept less efficiently (p < .03), and spent longer awake after sleep onset (p < .05). The polysomnographs of

seven patients with CFS and one healthy subject were regarded as significantly abnormal. Five patients and

one healthy subject had difficulty maintaining sleep. One patient had a disorder of both initiating and

maintaining sleep and one patient woke early. CONCLUSIONS: Patients with "pure" CFS complain of

unrefreshing sleep but only a minority have a clearly abnormal polysomnograph. The most common

abnormality is of long periods spent awake after initial sleep onset. Although sleep abnormalities may play

a role in the etiology of CFS, they seem to be unlikely to be an important cause of daytime fatigue in the

majority of patients. However, pharmacological and behavioral methods that improve sleep quality may be

an important component of a pragmatically based treatment package for patients who do have abnormal

sleep.

The objective was to determine if a cluster of chronic fatigue syndrome (CFS)-like illness had occurred

among employees in two large state office buildings in northern California, and to identify risk factors for

and features of fatiguing illness in this population. DESIGN: case-control study. POPULATION AND

SETTING: Over 3300 current employees in two state office buildings and employees in a comparable

"control" building. Information was collected on demographic and occupational variables, the occurrence of

fatiguing illness for at least one month in the previous year, and the presence of 36 symptoms. A total of

3312 (82%) of 4035 employees returned questionnaires. Overall, 618 (18.7%) persons reported fatigue

lasting at least one month; including 382 (11.5%) with fatigue of at least six months' duration and 75

(2.3%) with symptoms compatible with a CFS-like illness. Independent risk factors for fatigue lasting one

month or longer were found to be Native American ethnicity (OR 2.4, CI 1.1,5.3), Hispanic ethnicity (OR

1.7, CI 1.3,2.3), female sex (OR 1.5, CI 1.2,1.9), gross household incomes of less than $50,000 (OR 1.3, CI

1.1,1.6), and less than a college education (OR 1.3, CI 1.1,1.6). Similar risks were observed for persons

who reported fatigue lasting six months or longer. Female sex (OR 3.2, CI 1.7, 6.4) was the only

independent risk factor found for those persons classified as having a CFS-like illness. Case prevalence

rates for all three categories of fatigue, as determined by multivariate analysis, were not significantly

different among buildings. Despite finding a substantial number of employees with fatiguing illness in the

two state office buildings, the prevalence was not significantly different than that for a comparable control

building. Previously unidentified risk factors for fatigue of at least one month and at least six months

identified in this population included Hispanic ethnicity, not having completed college, and income below

$50,000.


ME Research UK — Database of Research Publications 1997

should have initial period of

rest before gradual increase

in activity.

discussion 948 Comment on:

BMJ. 1997 Jun

7;314(7095):1647-52

Erratum in: BMJ 1997 Nov

1;315(7116):1165

Shepherd C. Chronic fatigue syndrome. Lancet 1997 Jan

4;349(9044):57-8 comment

on: Lancet. 1996 Nov

16;348(9038):1384-5

Shepherd C.

Disagreements still exist over

the chronic fatigue syndrome.

BMJ 1997 Jan

11;314(7074):146

Shepherd C. Chronic fatigue syndrome. Prof Nurse 1997

Aug;12(11):827 Comment

on: Prof Nurse. 1997

May;12(8):578-81

Sheridan TF

Shorter E.

Simpson M, Bennett A,

Holland P.

Simpson M.

History of Medicine

Program, Faculty of

Medicine, University of

Toronto, Ontario, Canada.

Disability Policy and CFIDS

A Washington Perspective

Somatization and chronic

pain in historic perspective.

Chronic fatigue

syndrome/myalgic

encephalomyelitis as a

twentieth-century disease:

analytic challenges.

A body with chronic fatigue

syndrome as a battleground

for the fight to separate from

the mother.

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 63 - 67

Clin Orthop 1997

Mar;(336):52-60

J Anal Psychol 1997

Apr;42(2):191-9

J Anal Psychol 1997

Apr;42(2):201-16

"Disability Policy and CFIDS: A Washington Perspective" provides a follow-up to Mr. Sheridan's remarks

at the American Association for Chronic Fatigue Syndrome's clinical conference in San Francisco on

October 16, 1996. In this article, Mr. Sheridan explains that the difficulty for people with CFIDS (PWCs) in

obtaining disability benefits stems from the fact that disability determination is based on a person's

functional impairments resulting from a particular diagnosis. In other words, the Social Security

Administration does not consider a CFIDS diagnosis alone sufficient criteria to win a disability claim. The

article also describes the advocacy efforts carried out over the past five years by The CFIDS Association of

America and The Sheridan Group and the achievements of that collaboration. Mr. Sheridan concludes his

article with advice for PWCs who are considering an application for SSA disability benefits.

Practitioners today are confronted with an avalanche of difficult to treat patients with chronic pain for 2

reasons: (1) The culture increasingly encourages patients to conceive vague and nonspecific symptoms as

evidence of real disease and to seek specialist help for them; and (2) the rising ascendancy of the media and

the breakdown of the family encourage patients to acquire the fixed belief that they have a given illness,

often a trendy nondisease such as repetition strain injury or chronic fatigue syndrome. In historic terms,

many of these complaints, especially sensory ones featuring chronic pain and chronic fatigue, are relatively

new. Patients tend to adopt them on the basis of what the culture considers to be legitimate illness, whereby

different patterns exist for men and women.

The challenges of chronic fatigue syndrome (often called myalgic encephalomyelitis, especially in the UK)

(CFS/ME) to analytical and medical approaches are connected with our inability to understand its

distressing somatic symptoms in terms of a single identifiable and understandable disease entity. The

evidence for the roles of viral aetiologies remains inconclusive, as does our understanding of the

involvement of the immune system. The history and social context of CFS/ME, and its relation to

neurasthenia and psychasthenia are sketched. A symbolic attitude to the condition may need to be rooted in

an awareness of psychoid levels of operation, and the expression and spread of CFS/ME may sometimes be

aided by the ravages of projective identification. Psychic denial, sometimes violent, in sufferers (especially

children and adolescents) and their families may be important in the aetiology of CFS/ME. We draw out

common threads from psychodynamic work with five cases, four showing some symptomatic improvement,

analytic discussions of three cases being presented elsewhere in this issue of JAP.

I describe the therapy of a 20-year-old women who believed that her difficulties in concentrating and

remembering were caused by her "ME' (Myalgic encephalomyelitis, Chronic fatigue syndrome, or CFS).

She had been fathered by a man who never left his own wife. Work with her dreams revealed a within-body

drama in which she was locked in an unspeakable fight to the death with her mother. Her symptoms

improved after parallels between a dream and an accident showed her own self-destructive hand in her

story. Another dream, reflecting her first 'incestuous' affair, showed her search for her original father-self as

someone separate from mother, and a later affair provided a between-body drama, helping her to own the

arrogant and abject traits she had before seen only as her mother's. I show how we worked in the area of

Winnicott's first 'primitive agony' as experienced by a somatizing patient, stuck in a too-close destructive


ME Research UK — Database of Research Publications 1997

Smits MG, Nagtegaal JE,

Swart AC.

Sobetzko HM, Stark FM.

Spring SB, Eveline Lee

Tierney, Heidi M. Jolson

Strom SS, Baldwin BJ,

Sigurdson AJ, Schusterman

MA.

Suhadolnik RJ, Peterson

DL, O'Brien K, Cheney

PR, Herst CV, Reichenbach

NL, Kon N, Horvath SE,

Iacono KT, Adelson ME,

De Meirleir K, De Becker

P, Charubala R, Pfleiderer

W.

Department of Epidemiology,

The University of Texas M.

D. Anderson Cancer Center,

Houston 77030, USA.

Department of Biochemistry,

Temple University School of

Medicine, Philadelphia, PA,

USA.

[Chronic fatigue

syndrome].[article in Dutch]

["Chronic fatigue

syndrome"].[article in

German]

Meeting Reports:

Development of Outcome

Measures for Therapeutic

Trials of Chronic Fatigue

Syndrome

Cosmetic saline breast

implants: a survey of

satisfaction, breast-feeding

experience, cancer screening,

and health.

Biochemical evidence for a

novel low molecular weight

2-5A-dependent RNase L in

chronic fatigue syndrome.

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2359-60

Nervenarzt 1997

Nov;68(11):924-5 Comment

on: Nervenarzt. 1996

Sep;67(9):711-20

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 69 - 95

Plast Reconstr Surg 1997

Nov;100(6):1553-7

J Interferon Cytokine Res

1997 Jul;17(7):377-85

relationship with her mother-body. I discuss how analytical work can be done with the primitive affects and

conflicts against which the ME symptoms may be defending.

"The chronic fatigue syndrome (CFS) is a clinically defined condition characterized by severe disabling

fatigue and a combination of symptoms that prominently features self-reported impairments in

concentration and short-term memory, sleep disturbances and musculoskeletal pain" (1). The variability of

the course and severity of CFS combined with slow and infrequent full recovery and the lack of a defined

etiology have complicated the implementation of therapeutic clinical trials. The goal of the workshop was

to begin a systematic consideration of clinical trials issues and outcome measures that could be used to

evaluate CFS therapies in a definitive manner for safety and efficacy. The focus of the workshop was on

common issues applicable across therapies rather than on the merits of individual therapies. Careful study

design is critical to all trials. New methods and measures of health status will aid in determining the extent

of change related to therapeutic interventions. Approaches and methods used in the study and therapy of

other chronic illnesses may provide important insights for designing clinical trials and choosing outcome

measures for CFS interventions. Short-term outcomes in small groups of patients need to be validated by

other research groups, by additional and even larger studies, and by long-term studies. To insure enrollment

and compliance, patient concerns need to be considered in study design.

Saline breast implants have been used for the past 30 years for cosmetic and reconstructive purposes. Data

based on a large number of patients are needed to evaluate patient satisfaction, cancer screening practices,

problems associated with breast-feeding, and health effects. We conducted a follow-up study of 292

cosmetic saline breast implant patients from Texas and Louisiana who consented to a telephone interview.

Using a Likert scale, we measured the patients' degree of satisfaction with the implants. The results

indicated that 80.5 percent were satisfied, 73.3 percent would recommend saline breast implants to others,

and 65.1 percent felt that implants improved their quality of life. The extent of satisfaction was independent

of the number of additional surgeries, age at implant, and follow-up time. Mammography use and breast

self-examination were reported with high frequency in this survey. Ninety-one percent of study participants

who were between 40 and 49 years of age at time of interview and 94 percent of those 50 or older reported

having had at least one mammogram. Breast self-examination was practiced by 75 percent of the women,

and 61 percent reported checking their breasts at least once a month. Of the 46 women who had children

after augmentation, 28 reported breast-feeding and 8 (28.6 percent) reported having implant-related

problems. The patients were asked to provide information regarding a series of conditions for which they

sought medical attention. They reported: atypical rheumatoid syndrome (n = 1), Sjogren syndrome (n = 1),

atypical autoimmune disorder (n = 1), and chronic fatigue syndrome (n = 2). Overall, women who elected

to have saline breast implants were satisfied with their augmentations, had mammograms and performed

breast self-examinations more often than nonaugmented women. A few had problems when breast-feeding

that could be related to their implants. There were no reports of breast cancer, but five women reported

autoimmune conditions.

Previous studies from this laboratory have demonstrated a statistically significant dysregulation in several

key components of the 2',5'-oligoadenylate (2-5A) synthetase/RNase L and PKR antiviral pathways in

chronic fatigue syndrome (CFS) (Suhadolnik et al. Clin Infect Dis 18, S96-104, 1994; Suhadolnik et al. In

Vivo 8, 599-604, 1994). Two methodologies have been developed to further examine the upregulated

RNase L activity in CFS. First, photoaffinity labeling of extracts of peripheral blood mononuclear cells

(PBMC) with the azido 2-5A photoaffinity probe, [32P]pApAp(8-azidoA), followed by

immunoprecipitation with a polyclonal antibody against recombinant, human 80-kDa RNase L and analysis

under denaturing conditions. A subset of individuals with CFS was identified with only one 2-5A binding

protein at 37 kDa, whereas in extracts of PBMC from a second subset of CFS PBMC and from healthy

controls, photolabeled/immunoreactive 2-5A binding proteins were detected at 80, 42, and 37 kDa. Second,


ME Research UK — Database of Research Publications 1997

Sykes R. Chronic fatigue syndrome. Br J Psychiatry 1997

Oct;171:393

The chronic fatigue

syndrome and

hyperventilation.

Bazelmans E, Bleijenberg

G, Vercoulen JH, van der

Meer JW, Folgering H.

Department of Medical

Psychology, University

Hospital Nijmegen, The

Netherlands.

Erratum in: J Psychosom Res

1998 Mar-Apr;44(3-4):517

J Psychosom Res 1997

Oct;43(4):371-7

Tiersky LA, Johnson SK,

Lange G, Natelson BH,

DeLuca J.

Twemlow SW, Bradshaw

SL Jr, Coyne L, Lerma BH.

Uslan D

van der Meer JW, Elving

LD.

Department of Physical

Medicine and Rehabilitation,

UMDNJ-New Jersey Medical

School, Kessler Institute for

Rehabilitation, West Orange

07052, USA.

University of Kansas School

of Medicine, Wichita, USA.

Academisch Ziekenhuis, afd.

Algemeen Interne

Geneeskunde, Nijmegen.

Neuropsychology of chronic

fatigue syndrome: a critical

review.

Patterns of utilization of

medical care and perceptions

of the relationship between

doctor and patient with

chronic illness including

chronic fatigue syndrome.

Perspectives on CFS and

Impairment Proposed

Guidelines for Disability

Determination

[Chronic fatigue--'tired with

23 i's'].[article in Dutch]

J Clin Exp Neuropsychol

1997 Aug;19(4):560-86

Psychol Rep 1997

Apr;80(2):643-58

Journal of Chronic Fatigue

Syndrome 1997: 3(4): 75 - 85

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1505-

7Comment in: Ned Tijdschr

Geneeskd. 1997 Nov

29;141(48):2358-9 Ned

Tijdschr Geneeskd. 1997

Nov 29;141(48):2360

analytic gel permeation HPLC was completed under native conditions. Extracts of healthy control PBMC

revealed 2-5A binding and 2-5A-dependent RNase L enzyme activity at 80 and 42 kDa as determined by

hydrolysis of poly(U)-3'-[32P]pCp. A subset of CFS PBMC contained 2-5A binding proteins with 2-5Adependent

RNase L enzyme activity at 80, 42, and 30 kDa. However, a second subset of CFS PBMC

contained 2-5A binding and 2-5A-dependent RNase L enzyme activity only at 30 kDa. Evidence is

provided indicating that the RNase L enzyme dysfunction in CFS is more complex than previously

reported.

Chronic fatigue syndrome (CFS) is characterized by severe fatigue, lasting for at least 6 months, for which

no somatic explanation can be found. Because hyperventilation can produce substantial fatigue, it seems

worthwhile to investigate the relationship between it and CFS. It might be hypothesized that

hyperventilation plays a causal or perpetuating role in CFS. CFS patients, non-CFS patients known to

experience hyperventilation, and healthy controls were compared on complaints of fatigue and

hyperventilation. CFS patients and non-CFS patients known to experience hyperventilation offered

substantial complaints of fatigue and hyperventilation, both to a similar degree. Physiological evidence of

hyperventilation was found significantly more often in CFS patients than in healthy controls. However, no

significant differences between CFS patients with and CFS patients without hyperventilation were found on

severity of fatigue, impairment, number of complaints, activity level, psychopathology, and depression. It is

concluded that hyperventilation in CFS should probably be regarded as an epiphenomenon.

This article provides a comprehensive and critical review of the neuropsychological and related literature on

chronic fatigue syndrome (CFS). Despite the methodological limitations observed in several studies, some

consistent findings are noted. The most consistently documented neuropsychological impairments are in the

areas of complex information processing speed and efficiency. General intellectual abilities and higher

order cognitive skills are intact. Emotional factors influence subjective report of cognitive difficulty,

whereas their effect on objective performance remains uncertain. Although the neuropathological processes

underlying cognitive dysfunction in CFS are not yet known, preliminary evidence suggests the involvement

of cerebral white matter. Directions for future research are outlined. Review, Academic

To what extent do personal constructs affect the relationship between doctor and patient when the ill patient

does not readily recover with treatment Questionnaires were returned anonymously by 609 patients with a

self-reported diagnosis of chronic fatigue syndrome, who were considered chronically ill. Findings were

compared with those of an earlier study of a population of 397 general medical patients. The chronically ill

patients lost an average of 65 days of work per year due to illness compared to general medical patients

who missed six or fewer days per year because they were ill. The chronically ill patients also reported a

66% higher frequency of iatrogenic illness, spent more money on health care, took more medication, saw

more specialists, and were more litigious than the general medical population. Research suggested several

patterns of relationships between doctors and patients, and attitudes to health and illness, which may alert

doctors to patients' perceptions, beliefs, encoded constructs, and patterns of relating that affect responses to

treatment. More attention by doctors to patients who are experiencing the stress of chronic illness is

indicated.

Chronic Fatigue syndrome (CFS) is a difficult condition for which to determine work limitations and

disability. This paper discusses the current problems in the state-of-the-art, and proposes framework

standards for multi-disciplinary rehabilitation efforts to assess, prevent or limit disability, and multidisciplinary

standards for disability determination

Two patients, a woman aged 32 years and a man aged 49, presented with severe chronic fatigue. The

woman had chronic fatigue syndrome; she recovered slowly. The man suffered from a pituitary adenoma

producing follicle stimulating hormone; he recovered after transsphenoidal hypophysectomy. In patients

with chronic fatigue, the history and a thorough physical examination to exclude underlying illness are very

important; secondary symptom criteria must not be overemphasized (as is the case with the Holmes and

Fukuda criteria), chronic fatigue syndrome should not be diagnosed if the condition has a shorter duration

than 6 months, but it should be diagnosed if the clinical picture is compatible. The prognosis is not poor: in

patients with a median disease duration of 4.5 years, 20% show significant improvement over an 18-month


ME Research UK — Database of Research Publications 1997

van der Meer JW, Rijken

PM, Bleijenberg G,

Thomas S, Hinloopen RJ,

Bensing JM.

van der Meer JW.

Afd. Algemeen Interne

Geneeskunde, Academisch

Ziekenhuis, Nijmegen.

Academisch Ziekenhuis, afd.

Algemeen Interne

Geneeskunde, Nijmegen.

[Indications for management

in long-term, physically

unexplained fatigue

symptoms].[article in Dutch]

[Chronic fatigue

syndrome].[article in Dutch]

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1516-

9Comment in: Ned Tijdschr

Geneeskd. 1997 Nov

29;141(48):2361-2 Ned

Tijdschr Geneeskd. 1997

Nov 29;141(48):2362-3

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1507-9

van der Meer JW. Chronic fatigue syndrome. Eur J Clin Invest 1997

Apr;27(4):255-6 Comment

on: Eur J Clin Invest. 1997

Apr;27(4):257-67

Van Dishoeck EA.

Van Houdenhove B,

Fischler B, Neerinckx E.

Vedhara K, Llewelyn MB,

Fox JD, Jones M, Jones R,

Clements GB, Wang EC,

Smith AP, Borysiewicz LK.

Vercoulen JH, Bazelmans

E, Swanink CM, Fennis JF,

Galama JM, Jongen PJ,

Hommes O, Van der Meer

JW, Bleijenberg G.

Department of Medicine,

University of Wales College

of Medicine, Cardiff, UK.

k.vedhara@bristol.ac.uk

Department of Medical

Psychology, University

Hospital Nijmegen, The

Netherlands.

[Chronic fatigue

syndrome].[article in Dutch]

[Chronic fatigue

syndrome].[article in Dutch]

Consequences of live

poliovirus vaccine

administration in chronic

fatigue syndrome.

Physical activity in chronic

fatigue syndrome: assessment

and its role in fatigue.

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2358-9

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1505-7

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2360-1

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1510-2

J Neuroimmunol 1997

May;75(1-2):183-95

J Psychiatr Res 1997 Nov-

Dec;31(6):661-73

period.

In meetings arranged by the minister of Public Health, Welfare and Sports between general practitioners

and specialists concerning chronic fatigue syndrome (CFS), suggestions for the diagnosis, treatment and

assistance and support of patients with protracted physically unexplained fatigue symptoms, were

established in the light of current scientific insight. The term 'CFS' is applicable in cases of fatigue

complaints, of at least 6 months' standing, reported by the patient himself and evaluated medically, for

which no physical explanation has been found and which cause considerable disabilities in professional

social and/or personal functioning. The management depends on the duration of the illness. A distinction is

made between an acute phase (up to one month after the first consultation; the policy is mostly

expectative), a subacute phase (until 6 months after the onset of the complaints and disabilities; the

management is aimed at making the patient accept the condition and persuading him or her to make an

effort to promote health) and a chronic phase (from 6 months after the onset of the complaints and

disabilities; the management is aimed at health-promoting behaviour and cognitions). Further (laboratory)

examinations are useful only if the symptoms have not disappeared after one month (this is the case in

approximately 20% of the patients); such examinations may be useful in older patients earlier. It is

important that the CFS patient learns to realize that it is useless to continue to spend energy on searching

for causes and possible therapies, but that he should try to promote his own health, for instance by means of

a quantified programme of activities linked to a time schedule (instead of to a level of fatigue).

Chronic fatigue syndrome is a controversial disease entity. Opinions range from non-disease via psychiatric

disorder to a somatic disturbance. Somatic pathogenetic hypotheses include persisting infections,

intoxications, metabolic or immunologic disturbances, nervous system diseases and endocrine pathology.

None of these hypotheses has been substantiated as yet. Psychological factors are important in the course of

the disorder and can be used in the therapeutic approach of patients with chronic fatigue syndrome.

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in

a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7)

conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with

clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between

patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell

subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine

group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was

evidence of altered immune reactivity and virus clearance. Randomized Controlled Trial

This paper describes the assessment of physical activity in chronic fatigue syndrome (CFS) and

investigated the following questions: Do patients with CFS have low levels of physical activity; is there a

relationship between actual level of physical activity and fatigue; can self-report measures adequately

assess actual level of physical activity; what is the role of cognitions with respect to physical activity; and

are results with respect to physical activity specific to CFS Three different types of activity measures were

used: self-report questionnaires, a 12-day self-observation list, and a motion-sensing device (Actometer)

which was used as a reference for actual activity level. Fifty-one patients with CFS, 50 fatigued patients


ME Research UK — Database of Research Publications 1997

Versluis RG, de Waal MW,

Opmeer C, Petri H,

Springer MP.

Vojdani A, Ghoneum M,

Choppa PC, Magtoto L,

Lapp CW.

Vollmer-Conna U, Hickie I,

Hadzi-Pavlovic D, Tymms

K, Wakefield D, Dwyer J,

Lloyd A.

Rijksuniversiteit, vakgroep

Huisartsgeneeskunde,

Leiden.

Immunosciences Laboratory

Inc., Beverly Hills,

California, USA.

Inflammation Research Unit,

School of Pathology,

University of New South

Wales, Sydney, Australia.

[Prevalence of chronic

fatigue syndrome in 4 family

practices in Leiden].[article

in Dutch]

Elevated apoptotic cell

population in patients with

chronic fatigue syndrome:

the pivotal role of protein

kinase RNA.

Intravenous immunoglobulin

is ineffective in the treatment

of patients with chronic

fatigue syndrome.

Ned Tijdschr Geneeskd 1997

Aug 2;141(31):1523-6

J Intern Med 1997

Dec;242(6):465-78Comment

in: J Intern Med. 1999

Apr;245(4):409-10

Am J Med 1997

Jul;103(1):38-43

with multiple sclerosis (MS), and 53 healthy subjects participated in this study. Although none of the selfreport

questionnaires showed high correlations with the Actometer, questionnaires that require simple

ratings of specified activities were related to the Actometer and can be used as acceptable substitutes, in

contrast to instruments that require general subjective interpretations of activity that had low or nonsignificant

correlations with the Actometer. Actometer results showed that CFS patients and MS patients

had similar activity levels and both groups were significantly less active than healthy subjects. Compared to

MS patients, CFS patients were more likely to indicate that they had been less active than other persons

they knew. Activities which patients expected to result in higher fatigue levels were less frequently

performed. Patients with CFS had significantly higher scores on this measure than MS patients and healthy

subjects. Low levels of physical activity were related to severe fatigue in CFS but not in MS. In conclusion,

although CFS patients have similar low activity levels than MS patients, there are also important

differences between both groups: in CFS cognitive factors are more prominently involved in producing the

low activity levels than in MS and in CFS patients activity level is related to fatigue but not in MS.

Randomized Controlled Trial

OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) in general practice.

DESIGN: Descriptive. SETTING: General practice and primary health care centres in Leyden region, the

Netherlands. METHOD: RNUH-LEO is a computerized database which contains the anonymous patient

information of one general practice (with two practitioners) and four primary health care centres. The

fourteen participating general practitioners were asked what International Classification of Primary Care

(ICPC) code they used to indicate a patient with chronic fatigue or with CFS. With these codes and with the

code for depression patients were selected from the database. It then was determined whether these patients

met the criteria of CFS by Holmes et al. RESULTS: The general practitioners used 10 codes. Including the

code for depression a total of 601 patients were preselected from a total of 23,000 patients in the database.

Based on the information from the patients' records in the database, 42 of the preselected patients were

selected who might fulfill the Holmes' criteria of CFS. According to the patients' own general practitioner,

25 of the 42 patients would fulfil the Holmes' criteria. The men:women ratio was 1:5. The prevalence of

CFS in the population surveyed was estimated to be at least 1.1 per 1,000 patients.

OBJECTIVES: A prominent feature of chronic fatigue syndrome (CFS) is a disordered immune system.

Recent evidence indicates that induction of apoptosis might be mediated in a dysregulated immune system

by the upregulation of growth inhibitory cytokines. Therefore, the purpose of this study was to evaluate the

apoptotic cell population, interferon-alpha (IFN-alpha) and the IFN-induced protein kinase RNA (PKR)

gene transcripts in peripheral blood lymphocytes (PBL) of CFS individuals, as compared to healthy

controls. SUBJECTS AND METHODS: PBL were isolated from CFS (n = 29) and healthy control

individuals (n = 15) and subjected to quantitative analysis of apoptotic cell population and cell cycle

progression by flow cytometry. Quantitative competitive polymerase chain reaction (Q/C PCR) and

Western blot analysis were used to assess the levels of PKR mRNA and protein in control and CFS

individuals. In addition, circulating IFN-alpha was measured by ELISA assay. RESULTS: Increased

apoptotic cell population was observed in CFS individuals, as compared to healthy controls (26.6 +/- 12.9%

and 9.9 +/- 4.2%, respectively). The increased apoptotic subpopulation in CFS individuals was

accompanied by an abnormal cell arrest in the S phase and the G2/M boundary of the cell cycle as

compared to the control group (8.6 +/- 1.2 to 22.8 +/- 2.4 and 3.6 +/- 0.82 to 24.3 +/- 3.4, respectively). In

addition, CFS individuals exhibited enhanced PKR mRNA and protein levels (mean basal level 3538 +/-

1050 and 2.7 +/- 0.26, respectively) as compared to healthy controls (mean basal level 562 +/- 162 and 0.89

+/- 0.18, respectively). In 50% of the CFS samples (n = 29) treated with 2-aminopurine (2-AP) (a potent

inhibitor of PKR) the apoptotic population was reduced by more then 50%. CONCLUSIONS: PKRmediated

apoptosis in CFS individuals may contribute to the pathogenesis and the fatigue symptomatology

associated with CFS.

PURPOSE: To determine whether the reported therapeutic benefit of intravenous immunoglobulin in

patients with chronic fatigue syndrome (CFS) is dose dependent. PATIENTS AND METHODS: Ninetynine

adult patients, who fulfilled diagnostic criteria for CFS, participated in this double-blind, randomized,

and placebo-controlled trial. Patients received intravenous infusions with either a placebo solution (1%

albumin) or one of three doses of immunoglobulin (0.5, 1, or 2 g/kg) on a monthly basis for 3 months,


ME Research UK — Database of Research Publications 1997

Vollmer-Conna U,

Wakefield D, Lloyd A,

Hickie I, Lemon J, Bird

KD, Westbrook RF.

von Mikecz A,

Konstantinov K, Buchwald

DS, Gerace L, Tan EM.

Vooren PH.

Wagner LI, Jason LA.

Inflammation Research Unit,

School of Pathology,

University of New South

Wales, Sydney, Australia.

u.vollmerconna@unsw.edu.au

Institut fur Umwelthygiene,

Heinrich Heine Universitat

Dusseldorf, Germany.

Medical College of

Wisconsin, Milwaukee, USA.

Cognitive deficits in patients

suffering from chronic

fatigue syndrome, acute

infective illness or

depression.

High frequency of

autoantibodies to insoluble

cellular antigens in patients

with chronic fatigue

syndrome.

[Chronic fatigue

syndrome].[article in Dutch]

Outcomes of occupational

stressors on nurses: chronic

fatigue syndrome--related

symptoms.

Br J Psychiatry 1997

Oct;171:377-81

Arthritis Rheum 1997

Feb;40(2):295-305 comment

in: Arthritis Rheum. 1997

Nov;40(11):2095-7

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2359

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1526-30

Nursingconnections 1997

Fall;10(3):41-9

followed by a treatment-free follow-up period of 3 months. Outcome was assessed by changes in a series of

self-reported measures (quality-of-life visual analog scales, standardized diaries of daily activities, the

profile of mood states questionnaire) and the Karnofsky performance scale. Cell-mediated immunity was

evaluated by T-cell subset analysis and delayed-type hypersensitivity (DTH) skin testing. RESULTS: No

dose of intravenous immunoglobulin was associated with a specific therapeutic benefit. Adverse reactions,

typically constitutional symptoms, were reported by 70% to 80% of patients, with no relationship to

immunoglobulin treatment. CONCLUSIONS: Intravenous immunoglobulin cannot be recommended as a

therapy for the treatment of CFS. A better understanding of the pathophysiology of this disorder is needed

before effective treatment can be developed. Randomized Controlled Trial

BACKGROUND: Patients with chronic fatigue syndrome (CFS) report neuro-psychological symptoms as a

characteristic feature. We sought to assess cognitive performance in patients with CFS, and compare

cognitive performance and subjective workload experience of these patients with that of two disease

comparison groups (non-melancholic depression and acute infection) and healthy controls. METHOD: A

computerized performance battery employed to assess cognitive functioning included tests of continuous

attention, response speed, performance accuracy and memory. Severity of mood disturbance and subjective

fatigue were assessed by questionnaire. RESULTS: All patient groups demonstrated increased errors and

slower reaction times, and gave higher workload ratings than healthy controls. Patients with CFS and nonmelancholic

depression had more severe deficits than patients with acute infection. All patient groups

reported more severe mood disturbance and fatigue than healthy controls, but patients with CFS and those

with acute infection reported less severe mood disturbance than patients with depression. CONCLUSIONS:

As all patients demonstrated similar deficits in attention and response speed, it is possible that common

pathophysiological processes are involved. The differences in severity of mood disturbance, however,

suggest that the pathophysiological processes in patients with CFS and acute infection are not simply

secondary to depressed mood.

OBJECTIVE: To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS),

by identification and characterization of autoantibodies. METHODS: Initial immunofluorescence

histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping

and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble

cellular components was determined by in situ extraction of soluble components and subsequent

immunofluorescence histochemistry studies on the extracted cell substrate. RESULTS: Of 60 CFS patients,

41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear

envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twentyeight

CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern

was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized

with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle

pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament

pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in

immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens

was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another

of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients

without chronic fatigue had a significantly lower frequency of such antibodies (17%). CONCLUSION: The

high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which

might help to distinguish CFS from other rheumatic autoimmune diseases.

Considering the types and number of occupational stressors involved in caring for patients, nurses may

represent a population at high risk for physical illnesses. A sample of 3400 nurses who belong to a

statewide or a national nurses organization were randomly chosen for participation. Of this group, 202

reported 6 months or more of debilitating fatigue and completed a three-page questionnaire assessing


ME Research UK — Database of Research Publications 1997

Watson WS, GT

McCreathm A. Chaudhuri,

Peter O. Behan

Wearden A, Appleby L.

Wessely S, Chalder T,

Hirsch S, Wallace P,

Wright D.

Wessely S.

Department of Psychiatry,

University Hospital of South

Manchester.

Department of Psychological

Medicine, King's College

School of Medicine and

Dentistry, London, England.

Institute of Psychiatry,

Department of Psychological

Medicine, King's College

Hospital, London, United

Kingdom.

Possible Cell Membrane

Transport Defect in Chronic

Fatigue Syndrome

Cognitive performance and

complaints of cognitive

impairment in chronic

fatigue syndrome (CFS).

The prevalence and

morbidity of chronic fatigue

and chronic fatigue

syndrome: a prospective

primary care study.

Chronic fatigue syndrome: a

20th century illness

Journal of Chronic Fatigue

Syndrome 1997: 3(3): 1 - 13

Psychol Med 1997

Jan;27(1):81-90

Am J Public Health 1997

Sep;87(9):1449-55

Scand J Work Environ

Health 1997;23 Suppl 3:17-

34

symptoms related to chronic fatigue syndrome (CFS) and comorbid medical conditions. This group (N =

202) was mailed a follow-up questionnaire 1 year later that reassessed symptoms of CFS and occupational

stressors. Many sampled nurses reported a high degree of occupationally related stress but did not report

CFS symptoms; however, perceived exposure to the threat of an accident as a nurse and poor physical

working conditions were significantly related to symptoms reported. These findings are consistent with

previous research.

Cardiac thallium-201 single photon emission computerised tomography has been carried out on 10 adult

patients with chronic fatigue syndrome. Seven of the patients had defects in the thallium tracer distribution

within the left ventricle; this was significantly greater than would be expected in a normal adult population.

Similar abnormal scans have been observed in patients with syndrome X, a condition which has a symptom

overlap with chronic fatigue syndrome. It has been suggested that an abnormally high efflux of cellular

potassium may be the cause of the abnormal scans in syndrome X, and it is proposed that this mechanism

may also have a role to play in chronic fatigue syndrome.

Patients with chronic fatigue syndrome (CFS) complain that they have difficulties with concentration and

memory but studies to date have not found consistent objective evidence of performance deficits. Two

groups of CFS patients, depressed and non-depressed, and healthy controls, were asked about concentration

problems in general and specifically when reading. CFS subjects were more likely than controls to report

that they had concentration problems when reading, that they needed to re-read text and that they failed to

take in what they were reading. Subjects then performed a task in which their reading behaviour and text

recall was measured. While all CFS subjects complained of general cognitive failures and of difficulties

with reading, only depressed CFS subjects recalled significantly less of the text than controls. Severity of

complaints about reading problems was not related to amount of text recalled, but was related to severity of

depressed mood. However, subjects were able to evaluate accurately their ability to remember the text

immediately after reading it and before being tested for recall. Additionally, subjects performed a pairedassociate

learning task on which no significant differences between the subject groups was found. It is

concluded that deficits in cognitive functioning in CFS patients are more likely to be found on naturalistic

than on laboratory tasks. Controlled Clinical Trial

OBJECTIVES: This study examined the prevalence and public health impact of chronic fatigue and

chronic fatigue syndrome in primary care patients in England. METHODS: There were 2376 subjects, aged

18 through 45 years. Of 214 subjects who fulfilled criteria for chronic fatigue, 185 (86%) were interviewed

in the case-control study. Measures included chronic fatigue, psychological morbidity, depression, anxiety,

somatic symptoms, symptoms of chronic fatigue syndrome, functional impairment, and psychiatric

disorder. RESULTS: The point prevalence of chronic fatigue was 11.3%, falling to 4.1% if comorbid

psychological disorders were excluded. The point prevalence of chronic fatigue syndrome was 2.6%, falling

to 0.5% if comorbid psychological disorders were excluded. Rates did not vary by social class. After

adjustment for psychological disorder, being female was modestly associated with chronic fatigue.

Functional impairment was profound and was associated with psychological disorder. CONCLUSIONS:

Both chronic fatigue and chronic fatigue syndrome are common in primary care patients and represent a

considerable public health burden. Selection bias may account for previous suggestions of a link with

higher socioeconomic status.

The chronic fatigue syndrome has become the fin de siecle illness, now getting similar attention to that of

neurasthenia, which dominated medical thinking at the turn of the century. Myalgic encephalomyelitis was

an early term introduced in the United Kingdom in 1957 for this state, but it had little or no public or

professional prominence. Until then "chronic fatigue had become invisible", with "no name, no known

etiology, no case illustrations or clinical accounts in the medical textbook, no ongoing research activity--

nothing to relate it to current medical knowledge". The reconstruction of chronic fatigue began in the mid-

1980s, with the emergence of "chronic Epstein-Barr virus syndrome", which was later converted to chronic

fatigue syndrome. The former term, which first emerged in the mid-1980s, is now regarded as a misnomer

and should be abandoned. In the popular American literature the term "chronic fatigue and immune

deficiency syndrome" is preferred by the most active of the patient lobbies, while myalgic

encephalomyelitis continues to be the usual label in the United Kingdom. The relevant research linking

chronic fatigue syndrome with somatization is reviewed in this article. Understanding the nature of


ME Research UK — Database of Research Publications 1997

White PD, Cleary KJ.

Wijlhuizen T, Hamerslag

M.

Yataco A, Talo H, Rowe P,

Kass DA, Berger RD,

Calkins H.

Ziem G, McTamney J.

Department of Psychological

Medicine, St Bartholomew's

and the Royal London

Medical School, UK.

Department of Medicine,

Johns Hopkins University

School of Medicine,

Baltimore, MD 21287, USA.

Occupational and

Environmental Medicine,

Baltimore, Maryland, USA.

An open study of the efficacy

and adverse effects of

moclobemide in patients with

the chronic fatigue syndrome.

Chronic fatigue

syndrome].[article in Dutch]

Comparison of heart rate

variability in patients with

chronic fatigue syndrome and

controls.

Profile of patients with

chemical injury and

sensitivity.

Int Clin Psychopharmacol

1997 Jan;12(1):47-52

Ned Tijdschr Geneeskd 1997

Nov 29;141(48):2361-2

Comment on: Ned Tijdschr

Geneeskd. 1997 Aug

2;141(31):1516-9

615: Clin Auton Res 1997

Dec;7(6):293-7

Environ Health Perspect

1997 Mar;105 Suppl 2:417-

36

somatization can still shed some light on the meaning of chronic fatigue at the end of the 20th century.

Review, Academic

There is a strong association between the chronic fatigue syndrome and both depressive illness and sleep

disturbance, but the efficacy of antidepressants is uncertain. We studied the efficacy and adverse effects of

moclobemide in patients with chronic fatigue syndrome, stratifying the sample both by co-morbid major

depressive illness and by sleep disturbance. Forty-nine patients with chronic fatigue syndrome were

recruited. Patients were given moclobemide up to 600 mg a day for 6 weeks. Four (8%) patients dropped

out, three because of adverse effects. Adverse effects wee otherwise mild and transient. On analysing the

whole sample, there were significant but small reductions in fatigue, depression, anxiety and somatic

amplification, as well as a modest overall improvement. The greatest improvement occurred in those

individuals who had a co-morbid major depressive illness, with seven out of 14 (50%) of such individuals

rating themselves as "much better" by 6 weeks, compared to six out of 31 (19%) of those who were not

depressed (31% difference, 95% CI 1-60%, P = 0.04). Sleep disturbance had no effect on outcome.

Moclobemide may be indicated in patients with chronic fatigue syndrome and a co-morbid major

depressive disorder. A randomized, placebo-controlled trial is needed to confirm this. These results do not

support moclobemide as an effective treatment of chronic fatigue syndrome in the absence of a major

depressive disorder.

Recent studies have reported a close association between chronic fatigue syndrome and neurally mediated

hypotension. We hypothesized that this association may result from an abnormality in autonomic function

among patients with chronic fatigue syndrome, which may be detectable using an analysis of heart rate

variability. We prospectively studied 19 patients who fulfilled the Centers for Disease Control criteria for

chronic fatigue syndrome and 11 controls. Each subject underwent a two-stage tilt-table test while wearing

a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt

using frequency domain parameters. In the baseline supine position, high frequency (HF) power, low

frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were

similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power,

and increase in the LH/HF ratio. In conclusion, autonomic function, as assessed using an analysis of heart

rate variability, does not differ in the baseline supine state, nor in response to upright tilt among patients

with chronic fatigue syndrome and healthy controls.

Patients reporting sensitivity to multiple chemicals at levels usually tolerated by the healthy population

were administered standardized questionnaires to evaluate their symptoms and the exposures that

aggravated these symptoms. Many patients were referred for medical tests. It is thought that patients with

chemical sensitivity have organ abnormalities involving the liver, nervous system (brain, including limbic,

peripheral, autonomic), immune system, and porphyrin metabolism, probably reflecting chemical injury to

these systems. Laboratory results are not consistent with a psychologic origin of chemical sensitivity.

Substantial overlap between chemical sensitivity, fibromyalgia, and chronic fatigue syndrome exists: the

latter two conditions often involve chemical sensitivity and may even be the same disorder. Other disorders

commonly seen in chemical sensitivity patients include headache (often migraine), chronic fatigue,

musculoskeletal aching, chronic respiratory inflammation (rhinitis, sinusitis, laryngitis, asthma), attention

deficit, and hyperactivity (affected younger children). Less common disorders include tremor, seizures, and

mitral valve prolapse. Patients with these overlapping disorders should be evaluated for chemical sensitivity

and excluded from control groups in future research. Agents whose exposures are associated with

symptoms and suspected of causing onset of chemical sensitivity with chronic illness include gasoline,

kerosene, natural gas, pesticides (especially chlordane and chlorpyrifos), solvents, new carpet and other

renovation materials, adhesives/glues, fiberglass, carbonless copy paper, fabric softener, formaldehyde and

glutaraldehyde, carpet shampoos (lauryl sulfate) and other cleaning agents, isocyanates, combustion

products (poorly vented gas heaters, overheated batteries), and medications (dinitrochlorobenzene for warts,


ME Research UK — Database of Research Publications 1997

intranasally packed neosynephrine, prolonged antibiotics, and general anesthesia with petrochemicals).

Multiple mechanisms of chemical injury that magnify response to exposures in chemically sensitive

patients can include neurogenic inflammation (respiratory, gastrointestinal, genitourinary), kindling and

time-dependent sensitization (neurologic), impaired porphyrin metabolism (multiple organs), and immune

activation.

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