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, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome

Abstract:

BACKGROUND: The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness.

METHODS: Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-lymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-lymphotropic viruses I and II.

RESULTS: Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or myalgias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of follow-up, almost all study subjects were able to return to pre-illness activity. None of the viruses evaluated–human T-lymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6–could be etiologically linked to these outbreaks.

CONCLUSION: Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis ofchronic fatigue syndrome is usually favorable.

Comment in: Human herpesvirus type 6 and chronic fatigue syndrome. [Arch Intern Med. 1993]

 

Source: Levine PH, Jacobson S, Pocinki AG, Cheney P, Peterson D, Connelly RR, Weil R, Robinson SM, Ablashi DV, Salahuddin SZ, et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Arch Intern Med. 1992 Aug;152(8):1611-6. http://www.ncbi.nlm.nih.gov/pubmed/1323246

 

Chronic fatigue syndrome in northern Nevada

Abstract:

The clinical and laboratory findings from studies of patients with chronic fatigue syndrome (CFS) from northern Nevada are summarized. Physicians caring for these patients have estimated that greater than 400 patients with CFS from northern Nevada and nearby communities in California were identified between 1984 and 1988.

As a result of these studies, a cluster of clinical and laboratory features associated with the illness in moderately to severely affected patients has been identified: profound fatigue of prolonged duration; cervical lymphadenopathy; recurrent sore throat and/or symptoms of influenza; loss of cognitive function manifested by loss of memory and loss of ability to concentrate; myalgia; impairment of fine motor skills; abnormal findings on magnetic resonance imaging brain scan; depressed level of antibody to Epstein-Barr virus (EBV) nuclear antigen; elevated level of antibody to EBV early antigen restricted component; elevated ratio of CD4 helper to CD8 suppressor cells; and strong evidence of association of this syndrome with infection with human herpesvirus 6.

More-serious and longer-lasting neurologic impairments, including seizures, psychosis, and dementia, have also been observed in some of these patients.

 

Source: Daugherty SA, Henry BE, Peterson DL, Swarts RL, Bastien S, Thomas RS. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S39-44. http://www.ncbi.nlm.nih.gov/pubmed/1850542

 

Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome

Abstract:

Natural killer (NK)3 cells are large granular lymphocytes that appear to play a significant role in the host’s defense against viral infection. We performed an extensive phenotypic and functional characterization of NK cells on 41 patients with the chronic fatigue syndrome (CFS), or “chronic active Epstein-Barr virus infection” syndrome, and on 23 age- and sex-matched asymptomatic control subjects in an attempt to further characterize this illness.

These studies demonstrated that a majority of patients with CFS have low numbers of NKH1+T3- lymphocytes, a population that represents the great majority of NK cells in normal individuals. CFS patients had normal numbers of NKH1+T3+ lymphocytes, a population that represents a relatively small fraction of NK cells in normal individuals.

When tested for cytotoxicity against a variety of different target cells, patients with CFS consistently demonstrated low levels of killing. After activation of cytolytic activity with recombinant interleukin 2, patients were able to display increased killing against K562 but most patients remained unable to lyse Epstein-Barr virus-infected B cell targets. Additional cytotoxicity experiments were carried out utilizing anti-T3 monoclonal antibody to block killing by NKH1+T3+ cells.

These experiments indicated that the NK cell that appears to be responsible for much of the functional activity remaining in patients with CFS belongs to the NKH1+T3+ subset, which under normal circumstances represents only approximately 20% of the NK cell population.

 

Source: Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, Komaroff AL, Ritz J. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol. 1987 Nov 15;139(10):3306-13. http://www.ncbi.nlm.nih.gov/pubmed/2824604