Category: Treatment

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome

Abstract:

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls.

Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6).

Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. http://www.ncbi.nlm.nih.gov/pubmed/8148461

 

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition.

In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined.

Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance.

After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

 

Source: Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, Thompson C, Loveless M, Shapiro DE, Elsasser W, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95. http://www.ncbi.nlm.nih.gov/pubmed/8148460

 

Clinical studies with the NOVA ISE for IMg2+

Abstract:

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE’s for IMg2+ in the diagnosis and treatment of disease states.

 

Source: Altura BT, Burack JL, Cracco RQ, Galland L, Handwerker SM, Markell MS, Mauskop A, Memon ZS, Resnick LM, Zisbrod Z, et al. Clinical studies with the NOVA ISE for Img2+. Scand J Clin Lab Invest Suppl. 1994;217:53-67. http://www.ncbi.nlm.nih.gov/pubmed/7939386

 

The chronic fatigue syndrome

Abstract:

CFIDS (chronic fatigue and immune disfunction syndrome) is also known as CFS (chronic fatigue syndrome), CEBV (chronic Epstein-Barr virus), M.E. (myalgic encephalomyelitis), yuppie flu and by other names.

It is a complex illness characterized by incapacitating fatigue (experienced as exhaustion and extremely poor stamina), neurological problems and a constellation of symptoms that can resemble many disorders, including; mononucleosis, multiple sclerosis, fibromyalgia, AIDS-related complex (ARC) and autoimmune diseases such as lupus. These symptoms tend to wax and wane, but any often severely debilitating and may last for many months or years. All sections of the population (including children) are at risk, but women under 45 seem to be most susceptible.

The investigators suggest that CFIDS results from dysfunction of the immune system. The exact nature of this dysfunction is not yet well defined, but it can generally be viewed as an unregulated or overactive state which is responsible for most of the symptoms. There is also evidence of some immune suppression in CFIDS. None of the treatments is consistently satisfactory, but some may be helpful: psychotherapy, physiotherapy, exercise programs, acupunctures, small doses of antidepressants, etc.

 

Source: Artsimovich NG, Chugunov VS, Kornev AV, Ivanova TM, Chugunov AV, Oprishchenko MA. The chronic fatigue syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 1994;94(5):47-50. [Article in Russian] http://www.ncbi.nlm.nih.gov/pubmed/7900453

 

Chronic fatigue syndrome

Abstract:

The authors followed up for a period of 1-14 years 52 patients with CFS who met the criteria outlined by Holmes. The group comprised 10 men and 42 women. In 15% of these patients after a mean period of 5.5 years thyroiditis was diagnosed. Complete recovery was recorded in 20%, improvement in 32% of the patients, on average after 7 years. In the course of treatment mainly immunomodulating preparations were used. Indication of these drugs was individual based on immunological examinations. The success was only partial. The clinical condition of the patients did not correlate with serological findings of IgM, IgA and IgG antibodies against VCA nor with antibodies against EA of the EBV virus.

 

Source: Fucíková T, Petanová J. Chronic fatigue syndrome. Vnitr Lek. 1993 Oct;39(10):995-1002. [Article in Czech] http://www.ncbi.nlm.nih.gov/pubmed/8236872

 

Treatment of the chronic fatigue syndrome. A review and practical guide

Abstract:

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe a syndrome of severe and disabling fatigue of uncertain aetiology associated with a variable number of somatic and/or psychological symptoms. CFS has been reported in most industrialised countries and is most prevalent in women aged between 20 and 50 years.

Despite occasional claims to the contrary, the aetiology of CFS remains elusive. Although abnormalities in tests of immune function and cerebral imaging have been described in variable numbers of CFS patients, such findings have been inconsistent and cannot be relied upon, either to establish or exclude the diagnosis. Thus, diagnosis rests on fulfillment of the Centers for Disease Control case definition which was revised in 1992. This case definition remains somewhat controversial, largely due to its subjectiveness.

The mainstay of treatment is establishing the diagnosis and educating the patient about the illness. An empathetic clinician can stop further consultations elsewhere (‘doctor shopping’) and subsequent excessive investigations, which frequently occur in such patients.

Most patients should undertake a trial of antidepressant therapy, even if major depression is not present. The choice of antidepressant drug should tailor the tolerability profile to relief of particular CFS symptoms, such as insomnia or hypersomnia. Failure to improve within 12 weeks warrants an alternative antidepressant agent of another class. Many other drugs have been reported anecdotally to be beneficial, but no therapy has been demonstrated to be reproducibly useful in double-blind, placebo-controlled clinical trials with an adequate duration of follow-up.

 

Source: Blondel-Hill E, Shafran SD. Treatment of the chronic fatigue syndrome. A review and practical guide. Drugs. 1993 Oct;46(4):639-51. http://www.ncbi.nlm.nih.gov/pubmed/7506650

 

Disagreeing on how to treat CFS patients

Comment on: Chronic fatigue syndrome. A fresh look at an old problem. [Can Fam Physician. 1993]

 

There are some unfortunate inaccuracies in the article “Chronic Fatigue Syndrome.”‘ While the general information is useful in a very basic sense, two of the so-called “fresh look” items are inaccurate and misleading.

First, Dr McSherry suggests that “Oral magnesium supplements are indicated for CFS patients with subnormal red blood cell magnesium levels….” Presumably this recommendation comes from Dr McSherry’s reference to the study done by Cox et al. In this paper, red blood cell magnesium levels were found to be lower in patients diagnosed with chronic fatigue syndrome (CFS) than in a matched normal group, and patients were found to improve with intramuscular injections of 50% magnesium sulphate (1 g in 2 mL) every week for 6 weeks. However, oral magnesium has not been tested for its effectiveness in patients with CFS. Dr McSherry’s recommendation to use oral magnesium is, therefore, inaccurate and misleading.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379656/pdf/canfamphys00111-0026b.pdf

 

Source: Leyton E. Disagreeing on how to treat CFS patients. Can Fam Physician. 1993 May;39:1022-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379656/

 

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial

Abstract:

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing.

RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens.

CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Comment in:

Treatment for chronic fatigue syndrome. [Am J Med. 1994]

Cognitive behavior therapy for chronic fatigue syndrome. [Am J Med. 1995]

Cognitive behavior therapy for chronic fatigue syndrome. [Am J Med. 1995]

 

Source: Lloyd AR, Hickie I, Brockman A, Hickie C, Wilson A, Dwyer J, Wakefield D. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med. 1993 Feb;94(2):197-203. http://www.ncbi.nlm.nih.gov/pubmed/8430715

 

Chronic fatigue syndrome and the treatment process

Abstract:

Fatigue is a common complaint in general practice and is often associated with psychiatric and psychosocial problems and demoralization. Although the Centers for Disease Control definition of chronic fatigue syndrome (CFS) excludes pre-existing psychiatric illness, common psychosocial problems short of a clinical disorder (such as irritability, difficulty in thinking, inability to concentrate, depression and sleep disturbance) overlap with the criteria for CFS.

Psychological states can affect the course of CFS or become confused in the patient’s and doctor’s mind with the course of infection. The core dilemma in practice is how aggressively to pursue a possible basis for CFS when it persists in the absence of an identifiable external cause. Possibilities for exploration are numerous and potentially expensive. In practice, the persistence of doctors depends on the patient’s illness behaviour, on financial and organizational factors, and on the culture of medical care and practice styles.

It is essential to differentiate the appropriate management of CFS from scientific study where intensive investigation may be warranted. In practice doctors should proceed in a manner that conveys concern, supports function, and avoids dysfunctional illness behaviour and inadvertent legitimization and reinforcement of disability.

 

Source: Mechanic D. Chronic fatigue syndrome and the treatment process. Ciba Found Symp. 1993;173:318-27; discussion 327-41. http://www.ncbi.nlm.nih.gov/pubmed/8491105

 

Pharmacological approaches to the therapy of chronic fatigue syndrome

Abstract:

Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms.

Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression.

Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials.

 

Source: McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Found Symp. 1993;173:280-7; discussion 287-97. http://www.ncbi.nlm.nih.gov/pubmed/8491103