Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

Abstract:

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase.

Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion.

For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls.

In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively).

These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

 

Source: Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. http://www.ncbi.nlm.nih.gov/pubmed/9710746

 

Chronic fatigue syndrome: a literature review from a physiatric perspective

Abstract:

To examine the literature on chronic fatigue syndrome (CFS), especially as it relates to cognitive deficits and exercise, more than 200 articles related to CFS were selected from computer-based research as well as pertinent articles noted in the references of individual articles. All were relevant articles on CFS, although articles in a foreign language were excluded. CFS is a controversial diagnosis of exclusion, but certain subgroups do appear to exist. It may represent multiple diseases or multiple stages of the same disease. Although cognitive deficits are commonly reported, the measured impairments are relatively subtle and are in the area of complex information processing speed, or efficiency.

Magnetic resonance imaging, single-photon emission computer tomography, and neuroendocrine studies present preliminary evidence suggestive of the cerebral involvement primarily in the white matter. The weakness and fatigue may be the result of alterations in the central nervous system, not in the peripheral muscles. However, it is hard to separate the documented weakness and endurance deficits from deconditioning.

Autonomic symptoms such as orthostatic intolerance and a predisposition to neurally mediated syncope may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both. The review points out the need for more carefully designed studies of CFS that focus on the relationship between neuropathology, psychopathology and neuropsychologic functioning. The role of exercise as a stimulus for exacerbation or in treatment needs to be further studied using clear diagnostic criteria as well as control groups that carefully match the activity level.

 

Source: Jain SS, DeLisa JA. Chronic fatigue syndrome: a literature review from a physiatric perspective. Am J Phys Med Rehabil. 1998 Mar-Apr;77(2):160-7. http://www.ncbi.nlm.nih.gov/pubmed/9558019

 

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

 

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768

 

Chronic fatigue syndrome–a review of the literature

Abstract:

Chronic fatigue syndrome is a clinical condition characterized by abnormal fatigue, subfebrile body temperature, sore throat, lymphadenopathy, arthralgia, myalgia and neuropsychiatric symptoms. Typically, the syndrome develops after a flu-like illness and is markedly exacerbated by exercise. The etiology is unknown and there is no single diagnostic test. The patients may have cognitive dysfunction, immunological and endocrinological abnormalities and abnormal mitochondria. Magnetic resonance imaging scans may show increased uptake of signals in the brain, and single photon emission computerized tomography reveals regional hypoperfusion of the brain. The author discusses similarities and distinctions between the syndrome and depression.

 

Source: Hamre HJ. Chronic fatigue syndrome–a review of the literature. Tidsskr Nor Laegeforen. 1995 Oct 10;115(24):3042-5. [Article in Norwegian] http://www.ncbi.nlm.nih.gov/pubmed/7570537

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is defined by symptoms and diagnosed without any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise, counseling, and medications may provide symptomatic relief.

 

Source: Klonoff DC. Chronic fatigue syndrome. Clin Infect Dis. 1992 Nov;15(5):812-23. http://www.ncbi.nlm.nih.gov/pubmed/1445980

 

Chronic fatigue syndrome: a joint paediatric-psychiatric approach

Comment on: Chronic fatigue syndrome: a joint paediatric-psychiatric approach. [Arch Dis Child. 1992]

 

SIR,-While agreeing that physical, psychological, and social factors must all be taken into account in the management of this complex and controversial syndrome I would disagree with Dr Margaret Vereker’s statement that no organic pathology can be detected to account for any of the symptoms. This conclusion has been made without reference to a number of research papers describing persisting viral infection, neuromuscular abnormalities in both structure and function, and immune system dysfunction.

Gow et al using polymerase chain reaction techniques, have been able to demonstrate the presence of enteroviral genome in muscle biopsies from a significant number of patients (53%) compared with controls (15%). None of the healthy control group in this study had evidence of viral particles in their muscle, this was only found in those with colonic or breast malignancies. Precisely what cytopathological effect this intracellular virus is having within muscle remains open to debate. However, Behan et al have published electron microscopic evidence of structural damage to the muscle mitochondria along with type II fibre atrophy; this is a finding which is not normally considered to be consistent with simple disuse.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/pdf/archdisch00632-0102a.pdf

 

Source: Shepherd C. Chronic fatigue syndrome: a joint paediatric-psychiatric approach. Arch Dis Child. 1992 Nov;67(11):1410. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/

 

Self help organization’s advice on myalgic encephalomyelitis

Comment on: Outcome in the chronic fatigue syndrome. [BMJ. 1992]

 

EDITOR,-I should like to assure Simon Wessely that neither the ME Association nor ME Action regards Michael Sharpe and colleagues’ findings in patients with chronic fatigue’ as another attack on its credibility. Nor do we see why the paper should “further sour relations between the organisations and the profession.”

As Wessely points out, the apparent relation between functional impairment and membership of a self help organisation at follow up does not mean that membership of such an organisation is responsible for the impairment. Aside from the fact that the study did not focus on myalgic encephalomyelitis, or on the work the ME Association does, Sharpe reassured us that there was no evidence of a causal relation between membership of a patient group and level of disability.

As regards the potential damage resulting from inaccurate information about myalgic encephalomyelitis, it is worth emphasising that the quote that illustrates this came from Nursing Standard and not from a magazine for patients. The British organisations have long been unhappy with the way the media have portrayed the illness and reviewed existing research, and it is often extremely difficult to get erroneous or biased information corrected. Sometimes we get a right of reply, but usually we don’t.

Finally, I wish to make clear that our current advice on exercise and stress is based on sound scientific research, the recommendations of our medical advisers, and 50 years’ experience. Since our aim is to help patients it would be ridiculous for us to ignore good research and to stick instead to outdated explanations, speculation, or even prejudice. No one gains from such a narrow minded approach, least of all us.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883373/pdf/bmj00091-0063a.pdf

 

Source: Hume MC. Self help organization’s advice on myalgic encephalomyelitis. BMJ. 1992 Sep 12;305(6854):649. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883373/

 

Follow up of patients presenting with fatigue to an infectious diseases clinic

Abstract:

OBJECTIVES: To determine the symptomatic and functional status during follow up of patients referred to hospital with unexplained fatigue and to identify patient variables associated with persistent functional impairment.

DESIGN: Follow up by postal questionnaire six weeks to four years (median 1 year) after initial clinical assessment of patients referred to hospital during 1984-8.

SETTING: Infectious diseases outpatient clinic in a teaching hospital.

PATIENTS: 200 consecutive patients with fatigue of uncertain cause for at least six weeks; 177 fulfilled the inclusion criteria.

MAIN OUTCOME MEASURES: Findings at initial assessment; current symptoms, beliefs about the cause of illness, coping behaviours emotional disorder, social variables including membership of self help organizations, and degrees of recovery and functional impairment from questionnaire responses.

RESULTS: 144 (81%) patients returned completed questionnaires. Initial assessment did not indicate the cause of fatigue, other than preceding infection. The proportion of patients with functional impairment was significantly smaller with longer follow up (33% (11/33) at two to four years, 73% (29/40) at six weeks to six months; chi 2 for trend = 12.5, df = 1; p less than 0.05). Functional impairment was significantly associated with belief in a viral cause of the illness (odds ratio = 3.9; 95% confidence interval 1.5 to 9.9), limiting exercise (3.2; 1.5 to 6.6), avoiding alcohol (4.5; 1.8 to 11.3), changing or leaving employment (3.1; 1.4 to 6.9), belonging to a self help organization (7.8; 2.5 to 23.9), and current emotional disorder (4.4; 2.0 to 9.3).

CONCLUSIONS: Short term prognosis for recovery of function was poor but improved with time. Most patients had made a functional recovery by two years after initial clinic attendance. Impaired functioning was more likely with certain patient characteristics. Prospective studies are required to clarify whether these associations are the consequences of a more disabling illness or indicate factors contributing to impaired function.

Comment in

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

 

Source: Sharpe M, Hawton K, Seagroatt V, Pasvol G. Follow up of patients presenting with fatigue to an infectious diseases clinic. BMJ. 1992 Jul 18;305(6846):147-52. http://www.ncbi.nlm.nih.gov/pubmed/1515828

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883193/

 

Chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is a poorly understood condition with nonspecific signs and symptoms, especially debilitating fatigue. Most patients can pinpoint the onset of their illness and usually describe a flu-like state. The search for an etiologic agent has focused on a number of viruses such as Epstein-Barr, enteroviruses, retroviruses, and human herpesvirus-6.

Evidence supports persistent viral infection in a small percentage of CFS patients. Immunologic abnormalities do exist in CFS, which indicate the presence of immune activation in CFS patients.

Although abnormal muscle biopsies have been found in some patients with CFS, strength and endurance appear normal, but perception of exertion may be abnormal. Patients with chronic fatigue have a high incidence of premorbid and concurrent psychiatric disorders, and on physical examination many often have reproducible tender points similar to fibromyalgic patients. Clinical evaluation should rule out other potential causes of fatigue, but elaborate diagnostic tests are seldom required.

Presently, no specific treatment exists for CFS. A cognitive behavioral approach with or without the use of tricyclics has been advocated. Patients should be encouraged to maintain functional status and should not be discouraged from exercise. Several medications have been tried but with no definite clinical benefit.

 

Source: Winters EG, Quinet RJ. Chronic fatigue syndrome. J La State Med Soc. 1992 Jun;144(6):260-70. http://www.ncbi.nlm.nih.gov/pubmed/1619343

 

Chronic fatigue syndrome: a joint paediatric-psychiatric approach

Comment in: Chronic fatigue syndrome: a joint paediatric-psychiatric approach. [Arch Dis Child. 1992]

 

Prolonged fatigue after an apparent viral infection, occurring sporadically or as an epidemic, has been described over the past 50 years. It has been given various names including Royal Free disease (1) and myalgic encephalomyelitis, but the preferred terms in the medical literature have been postviral fatigue syndrome (2) or chronic fatigue syndrome (CFS). (3)

However, the validity of this syndrome as a nosological entity has created a good deal of controversy and remains in doubt. (4) A constellation of symptoms make up the syndrome. There is fatigue of defined onset that is generally reported to follow a viral illness, often an influenza-like illness or an infection of the upper respiratory tract. The patient experiences profound fatigue with the initial illness and then fails to make the expected recovery, with fatigue that can persist over months or years. Fatigue is defined as a subjective sensation, which the patient often describes as tiredness or weariness and that occurs at rest. These patients also report a clear relationship of fatigue to activity. The term fatiguability has been used to describe the greater than normal fatigue that occurs after physical and sometimes after mental exertion in these patients. A great variety of associated symptoms have been described that include increased sleepiness, dizziness, vertigo, headache, difficulty in concentrating, sore throat, muscle weakness, and myalgia. The majority of patients have some emotional symptoms. There can be irritability and anxiety, tearfulness and depression. The fatigue and associated symptoms are of such severity as to impair significantly normal daily activities. There is a remarkable absence of physical signs and physical investigations fail to detect any organic pathology or current infection to account for the symptoms.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793327/pdf/archdisch00639-0088.pdf

 

Source: Vereker MI. Chronic fatigue syndrome: a joint paediatric-psychiatric approach. Arch Dis Child. 1992 Apr;67(4):550-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793327/