Mismatched double-stranded RNA: polyI:polyC12U

Abstract:

Ampligen [polyI:polyC12U] is a mismatched double-stranded RNA that acts by inducing interferon production (immunomodulator) and by activating an intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral). Ampligen, currently under development by Hemispherx Biopharma in the US, acts on the immunological system through T-lymphocyte stimulation and is indicated for the treatment of chronic fatigue syndrome and acquired immunodeficiency deficiency syndrome (AIDS), as part of the combined therapy. Ampligen is available for licensing worldwide.

In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for Ampligen for the potential treatment of chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee of 400,000 euros was paid pursuant to the terms of the option agreement and upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars.

In September 2003, Hemispherx Biopharma Inc. entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, Ampligen and Alferon N in the People’s Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with Ampligen for the treatment of HIV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes.

In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that will see Ampligen implemented in a protocol used in patients with relapsed EBV-positive Hodgkin’s Lymphoma.

In March 2002, Esteve and Hemispherx Biopharma entered into a collaborative agreement under which Esteve will be the sole distributor of Ampligen in Spain, Portugal and Andorra for the treatment of chronic fatigue syndrome. Under this agreement, in addition to other terms, Esteve will also collaborate in the drug product development by conducting clinical studies in Spain in patients coinfected with HIV/HCV.

In July 2001 Hemispherx Biopharma announced that it had formed a strategic alliance with Empire Health Resources for clinical trials of Ampligen in the treatment of HIV and hepatitis C virus infections. Empire Health Resources, a healthcare management firm, will be responsible for accrual and retention of patients for HIV trials, and protocols for trials in patients with hepatitis C or both HIV and hepatitis C infections.

Hemispherx has entered into a collaboration with RED Laboratories, and RED Laboratories NV expects that this will facilitate the continued development of Ampligen. Hemispherx has also entered into an agreement with Schering Plough to use a Schering facility as its principal manufacturing platform in the US. This agreement may be expanded to include other territories. Hemispherx and AOP Orphan Pharmaceuticals have signed a marketing agreement for Ampligen for the treatment of chronic fatigue syndrome for Austria, the Czech Republic, Poland and Hungary. In an arrangement between Hemispherx and Bioclones, Bioclones has certain marketing rights for Ampligen in the Southern Hemisphere, UK and Ireland.

In the US, Ampligen has been granted orphan drug status for the treatment of AIDS, renal cell carcinoma (phase II, completed), chronic fatigue syndrome (phase III) and invasive/metastatic malignant melanoma (phase II).

In August 2004, Hemispherx announced that it intends to use the proceeds from the private placement of company stock to complete the clinical work for its immunotherapeutics/ antivirals Ampligen and Oragens. Previously, Hemispherx submitted an application to the EMEA for the approval of Ampligen for the treatment of chronic fatigue syndrome; the first stage of th;) for the treatment of chronic fatigue syndrome; the first stage of the regulatory review has been cleared.

In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for Ampligen for the treatment of chronic fatigue syndrome in the EU, providing Hemispherx with 10 years of marketing exclusivity following the launch of the drug, as well as potential financial research benefits for the agent.

In February 2000, Crystaal Corporation (now Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to Ampligen in Canada, where it submitted an NDA for the agent for the treatment of chronic fatigue syndrome. In the meantime, Ampligen has been available since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of chronic fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix BioPharma).

Bioclones has initiated clinical studies with Ampligen for the treatment of chronic fatigue syndrome in Australia. The active substance for Ampligen is manufactured by F.H. Faulding Ltd.

Clinical treatment programmes for chronic fatigue syndrome in other Pacific Rim countries are planned. Ampligen is available for severe chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa. Hemispherx has developed a ‘ready-to-use’ liquid formulation of the drug and has begun treating patients with chronic fatigue syndrome in ongoing clinical trials. Hemispherx has also developed an oral version of the drug (Oragen), which is undergoing preclinical evaluation.

In February 2001, Hemispherx Biopharma announced that it was initiating phase II/III trials of Ampligen in the treatment of late-stage, multidrug-resistant strains of HIV in the European Union. Patients treated in these studies will have exhausted all other treatment options.

In July 2001, Hemispherx stated that Ampligen was being evaluated in a phase IIb trial in patients with HIV in the US. The trial, comprising two studies, REARMI and REARMII (Research/Evaluation of Ampligen for Retroviral Mutations I and II), will evaluate the ability of Ampligen to prevent the emergence of mutated, drug-resistant strains of the virus. ‘Several hundred’ patients currently on antiretroviral therapy and at risk of viral relapse will be enrolled at centres in Connecticut, New York, Florida and California.

A second phase IIb study evaluating the effect of Ampligen on structured treatment interruptions (STI) is also underway. Final results from this study were reported in December 2002. NIH sponsored studies of potential therapies for SARS have identified Ampligen as having unusually high and consistent antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease. Ampligen demonstrated very high potency at very low concentrations (0.4 microg/mL) and had a favourable safety profile.

In October 2003, Hemispherx announced that, based on these promising new results, the company will stockpile injectible and/or oral formats of Ampligen and Alferon N. Independent researchers have demonstrated the antiviral activity of Ampligen against flaviviruses (West Nile virus, Equine Encephalitis virus, Dengue fever virus and Japanese Encephalitis virus) as well as virus classes associated with bioterrorism. In an animal study, Ampligen was shown to prevent destruction of nerve cells, reduce virus concentrations in the brain and blood stream and increase survival rates. Researchers at the Rega Institute in Belgium have published results from an animal study demonstrating that Ampligen was superior at protecting mice against coxsackie B3 virus-induced myocarditis compared with pegylated interferon.

In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of Ampligen for the potential treatment and prevention of severe acute respiratory syndrome (SARS) and dreaded emerging viruses.

Copyright 2004 Adis Data Information BV

Source: [No authors listed] Mismatched double-stranded RNA: polyI:polyC12U. Drugs R D. 2004;5(5):297-304. http://www.ncbi.nlm.nih.gov/pubmed/15357629

 

 

Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial

Abstract:

CONTEXT: There is no established pharmacological treatment for the core symptoms of chronic fatigue syndrome (CFS). Galantamine hydrobromide, an acetyl cholesterone inhibitor, has pharmacological properties that might benefit patients with CFS.

OBJECTIVE: To compare the efficacy and tolerability of galantamine hydrobromide in patients with CFS.

DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial conducted June 1997 through July 1999 at 35 outpatient centers in the United Kingdom (n = 17), United States (n = 14), the Netherlands (n = 2), Sweden (n = 1), and Belgium (n = 1) involving 434 patients with a clinical diagnosis of CFS (modified US Centers for Disease Control and Prevention criteria).

INTERVENTIONS: A total of 89 patients were randomly assigned to receive 2.5 mg of galantamine hydrobromide; 86 patients, 5.0 mg; 91 patients, 7.5 mg; and 86 patients, 10 mg (these patients received medicine in the tablet form 3 times per day); a total of 82 patients received matching placebo tablets 3 times per day.

MAIN OUTCOME MEASURES: The primary efficacy variable was the global change on the Clinician Global Impression Scale after 4, 8, 12, and 16 weeks of treatment. Secondary outcomes were changes in core symptoms of CFS on the Chalder Fatigue Rating Scale, the Fibromyalgia Impact Questionnaire, and the Pittsburgh Sleep Quality Index; changes in quality of life on the Nottingham Health Profile; and assessment of plasma-free cortisol levels and cognitive performance on a computer-based battery of tests.

RESULTS: After 16 weeks, there were no statistically significant differences between any of the galantamine or placebo groups in clinical condition on the Clinician Global Impression Scale, or for any of the secondary end points. Exploratory regression analysis failed to detect any consistent prognostic factor that might have influenced the primary or any secondary outcome measures.

CONCLUSION: This trial did not demonstrate any benefit of galantamine over placebo in the treatment of patients with CFS.

Comment in:

Pharmacotherapy of chronic fatigue syndrome: another gallant attempt. [JAMA. 2004]

Chronic fatigue syndrome and the cholinergic hypothesis. [JAMA. 2004]

 

Source: Blacker CV, Greenwood DT, Wesnes KA, Wilson R, Woodward C, Howe I, Ali T. Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial. JAMA. 2004 Sep 8;292(10):1195-204. http://www.ncbi.nlm.nih.gov/pubmed/15353532

 

Altered central nervous system signal during motor performance in chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of this study was to determine whether brain activity of chronic fatigue syndrome (CFS) patients during voluntary motor actions differs from that of healthy individuals.

METHODS: Eight CFS patients and 8 age- and gender-matched healthy volunteers performed isometric handgrip contractions at 50% maximal voluntary contraction level. They first performed 50 contractions with a 10 s rest between adjacent trials–‘Non-Fatigue’ (NFT) task. Subsequently, the same number of contractions was performed with only a 5 s rest between trials–‘Fatigue’ (FT) task. Fifty-eight channels of surface EEG were recorded simultaneously from the scalp. Spectrum analysis was performed to estimate power of EEG frequency in different tasks. Motor activity-related cortical potential (MRCP) was derived by triggered averaging of EEG signals associated with the muscle contractions.

RESULTS: Major findings include: (i) Motor performance of the CFS patients was poorer than the controls. (ii) Relative power of EEG theta frequency band (4-8 Hz) during performing the NFT and FT tasks was significantly greater in the CFS than control group (P < 0.05). (iii) The amplitude of MRCP negative potential (NP) for the combined NFT and FT tasks was higher in the CFS than control group (P < 0.05) (iv) Within the CFS group, the NP was greater for the FT than NFT task (P<0.01), whereas no such difference between the two tasks was found in the control group.

CONCLUSIONS: These results clearly show that CFS involves altered central nervous system signals in controlling voluntary muscle activities, especially when the activities induce fatigue.

SIGNIFICANCE: Physical activity-induced EEG signal changes may serve as physiological markers for more objective diagnosis of CFS.

 

Source: Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH. Altered central nervous system signal during motor performance in chronic fatigue syndrome. Clin Neurophysiol. 2004 Oct;115(10):2372-81. http://www.ncbi.nlm.nih.gov/pubmed/15351380

 

Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan

Abstract:

For the last 15 years, we have tried to understand the pathophysiology of childhood chronic fatigue syndrome (CCFS) in Japan. In this condition, two major symptoms are important: easy fatigability and disturbed learning and memorization. In CCFS patients we clinically evaluated autonomic nervous system function, circadian rhythm of hormonal secretion (melatonin, cortisol and 3-endorphin), core body temperature, and sleep-wake pattern.

Most patients showed autonomic nervous system dysfunction and circadian rhythm disturbances, similar to those observed in jet lag. Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe. We analyzed the relationship between the laboratory data and clinical symptoms in CCFS.

 

Source: Miike T, Tomoda A, Jhodoi T, Iwatani N, Mabe H. Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan. Brain Dev. 2004 Oct;26(7):442-7. http://www.ncbi.nlm.nih.gov/pubmed/15351079

 

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies

Abstract:

The Chronic Fatigue Syndrome (CFS) is characterized by symptoms lasting for at least six months and accompanied by disabling fatigue. The etiology of CFS is still unclear.

At the National Center for Study of the Infectious Diseases Department of the Chieti University some immune investigations were performed with the purpose of detecting markers of the disease. CD4+, CD8+, NK CD56+ and B CD19+ lymphocytes were studied in 92 male and 47 female patients and in 36 control subjects. CFS patients were divided in three groups with a post-infectious onset (PI-CFS), an non post-infectious onset (NPI-CFS) and a non post-infectious onset with associated infections (NPI-CFS + AI).

Both CD4+ and CD8+ lymphocytes were reduced in the CFS patients. However, the CD4+/CD8+ ratio was increased in the CFS patients without difference between males and females. CD56+ cells of CFS patients were also reduced. In particular, blood CD56+ cells counts were significantly higher in PI-CFS patients than in the NPI-CFS subjects. These data confirm our preliminary results suggesting a key-role of a dysfunction of the immune system as a precipitating and-or perpetuating factor of the syndrome.

 

Source: Racciatti D, Dalessandro M, Delle Donne L, Falasca K, Zingariello P, Paganelli R, Pizzigallo E, Vecchiet J. Study of immune alterations in patients with chronic fatigue syndrome with different etiologies. Int J Immunopathol Pharmacol. 2004 May-Aug;17(2 Suppl):57-62. http://www.ncbi.nlm.nih.gov/pubmed/15345193

 

Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis

Abstract:

OBJECTIVE: To evaluate the prevalence of infection with Borna disease virus (BDV) in Chinese patients with chronic fatigue syndrome (CFS) and control subjects, and to discuss the etiological association between CFS and infection with BDV.

METHODS: The CDC (1994) diagnostic criteria for CFS were used for case definition. Sixty-one patients suffered from CFS were from 11 Provinces in China. To detect the antibody against BDV-p24 on the plasma samples from all cases and 73 healthy control subjects by Western-blotting analysis.

RESULTS: 7 of the sixty-one cases and 0 of the controls were sero-positive for BDV-p24 antibody, there was a statistical significant difference between the two groups (11.48% vs 0%; P less than 0.010).

CONCLUSION: Chinese patients with CFS showed sero-positive identifying BDV infection, by comparison, anti.BDV-p24 antibody prevalence in patients was significantly higher than in controls. An etiological association may exist between CFS and BDV infection.

 

Source: Li YJ, Wang DX, Zhang FM, Liu ZD, Yang AY, Ykuta K. Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2003 Dec;17(4):330-3. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/15340544

 

Chronic fatigue syndrome: a clinical and laboratory study with a well-matched control group

Comment on: Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group. [J Intern Med. 1995]

 

Dear Sir,

It is an ongoing debate whether concurrent occurrence of particular additional symptoms should be part of the definition of chronic fatigue syndrome (CFS) [1–5] or not. Studies on the similarities and differences between patients satisfying the various definitions are indispensable to solve this dispute.

Swanink et al. [6] studied CFS patients satisfying the criteria described by Sharpe et al. [3], i.e. additional symptoms may be present but are not required. Part of the group also satisfied the more stringent CFS criteria by the Centers for Disease Control (CDC) [1], which require the additional presence of at least eight specific symptoms. When the number of complaints was included as the covariate, no significant differences on fatigue severity, depression and functional impairment were found between CFS patients who fulfilled the CDC criteria and who did not. Furthermore, the authors remarked that the sole effect of applying the CDC symptom criteria to their study group is separating patients with few symptoms from patients with many symptoms.

These results are very misleading and have often been misinterpreted. The authors’ analysis of variance (anova) yielded a lot of significant differences between CDC–CFS and non-CDC–CFS patients. That these were lost in their subsequent analysis of covariance (ancova) is because the level of the covariate and the treatment (fulfilment of the CDC criteria) are highly dependent, as fulfilment of the CDC criteria requires the presence of at least nine symptoms (fatigue included). Because the ancova assumption that the covariate is statistically independent of the treatment is not met, the ancova results are artificial and have little practical meaning [7, 8].

What happened* is illustrated in Fig. 1. anova checks whether CDC–CFS and non-CDC–CFS patients have equal test score means  and inline image and inline image. ancova, however, checks the equality of adjusted test score means  and inline image and inline image. These are obtained by transporting inline image and inline image from the treatment covariate means  inline image and inline image and  along parallel regression lines to the grand covariate mean inline image. Thus ancova predicts if test score means of CDC–CFS and non-CDC–CFS patients would have been equal if both groups had exactly the same mean number of complaints. It provides an answer to a question that has no relevance – the mean number of complaints is inherently different for these two groups. In particular, Table 1 of the article learns that the grand covariate mean as reported with the standardized questionnaire equals  = 674/88 = 7.66: the adjusted mean  corresponds to a group of CDC–CFS patients that does not even exist in reality!

Figure 1.

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Difference between analysis of variance (anova) and analysis of covariance (ancova).anova compares the treatment means  and , whereas ancova compares the adjusted treatment means  and  corresponding to the same level of the covariate for both groups. Note that the grand covariate mean corresponds to a group of CDC–CFS patients that does not exist in reality.

Although their ancova was inappropriate, the authors’anova did result in valuable information.anova of CDC–CFS versus non-CDC–CFS yielded significant differences (at least P < 0.05) in concentration, activity, sleep and rest, ambulation, alertness behaviour, and recreation and pastimes, which according to the authors means that CDC–CFS patients are significantly more impaired in daily functioning. As the subjective fatigue subscale of the checklist individual strength (CIS-fatigue) easily reaches the extreme end of its scale in CFS samples (see e.g. [9, 10]), it is obvious that no significant differences in fatigue severity as measured by CIS-fatigue could be found. Generally speaking, assessing fatigue severity using a scale without this flaw may well result in different outcomes (see e.g. [10]).

Because the inadequate ancova made it appear that there are no clinical differences between CDC–CFS and non-CDC–CFS patients, this study has often been cited to permit leaving out additional symptom criteria when considering CDC–CFS. This has had major consequences for scientific research as well as for clinical practice. In scientific literature, non-CDC–CFS patients are labelled as having ‘a diagnosis of CFS according to the CDC criteria’ [10] or fulfilling ‘the CDC criteria for CFS’ [11], although other sources by the same authors explicitly state that they do not [12, 13]. In a large randomized study on cognitive behaviour therapy for CFS [14], one of the two reasons that patients without the required number of additional symptoms were included is that ‘patients who fulfilled the CDC-criteria did not differ concerning the severity of the complaints from patients who did not satisfy the CDC criteria’ [13]. The CFS definition used for clinical practice in large parts of the Netherlands [15] is based on CDC criteria, but patients without the required additional symptoms are also diagnosed CFS because ‘clinically this distinction has no meaning, as it has turned out from Dutch research’ [16]. This means that if the mistakes above would have been noted at an earlier stage, literally thousands of chronically fatigued patients might have had a different diagnosis in the Netherlands.

Apparently [13] the incorrect results of the article have also been presented during a recent meeting held for revising the latest CDC–CFS definition (presentation Bleijenberg, CDC consensus meeting, Atlanta 2000). To prevent more scientific research on CDC–CFS that disregards additional symptoms and more CFS definitions that are based on statistical errors rather than on data, it is important that the mistakes in the article are corrected as soon as possible.

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2004.01378.x/full

 

Source: Stouten B. Chronic fatigue syndrome: a clinical and laboratory study with a well-matched control group. J Intern Med. 2004 Sep;256(3):265-7; author reply 268-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2004.01378.x/full (Full article)

 

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome

Abstract:

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs.

To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT.

While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

 

Source: Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome. Auton Neurosci. 2004 Jun 30;113(1-2):55-62. http://www.ncbi.nlm.nih.gov/pubmed/15296795

 

Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability

Abstract:

BACKGROUND AND PURPOSE: Patients who experience pain, a symptom of chronic fatigue syndrome (CFS), often exhibit kinesiophobia (irrational fear of movement). The purpose of this study was to examine whether pain-related fear of movement is associated with exercise capacity, activity limitations, or participation restrictions in patients with CFS who experience widespread pain.

SUBJECTS AND METHODS: Sixty-four subjects met the inclusion criteria. All subjects fulfilled the 1994 Centers for Disease Control and Prevention case definition for CFS and experienced widespread myalgias or arthralgias. The subjects completed the Tampa Scale for Kinesiophobia-Dutch Version (TSK-DV) and the Dutch Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ). They then performed a maximal exercise test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Ventilatory factors were measured through spirometry. Correlations between the TSK-DV scores and both the exercise capacity data and the CFS-APQ scores were assessed using the Spearman rank correlation coefficient. Using the Mann-Whitney U test, the TSK-DV scores were compared between subjects who performed a maximal exercise stress test and those who did not perform the test.

RESULTS: Forty-seven subjects (73.4%) attained a total score of greater than 37 on the TSK-DV, indicating high fear of movement. Neither the exercise capacity data nor the CFS-APQ scores indicated a correlation with the TSK-DV scores (n=64). Subjects who did not perform a maximal exercise capacity test had more fear of movement (median TSK-DV score=43.0, interquartile range=10.3) compared with those who did perform a maximal exercise capacity test (median TSK-DV score=38.0, interquartile range=13.2; Mann-Whitney U-test score=322.5, z=-1.974, P=.048), but the correlation analysis was unable to reveal an association between exercise capacity and kinesiophobia in either subgroup.

DISCUSSION AND CONCLUSION: These results indicate a lack of correlation between kinesiophobia and exercise capacity, activity limitations, or participation restrictions, at least in patients with CFS who are experiencing widespread muscle or joint pain.

 

Source: Nijs J, Vanherberghen K, Duquet W, De Meirleir K. Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability. Phys Ther. 2004 Aug;84(8):696-705. http://ptjournal.apta.org/content/84/8/696.long (Full article)

 

Increased neutrophil apoptosis in chronic fatigue syndrome

Abstract:

BACKGROUND/AIMS: Many patients with chronic fatigue syndrome (CFS) have symptoms that are consistent with an underlying viral or toxic illness. Because increased neutrophil apoptosis occurs in patients with infection, this study examined whether this phenomenon also occurs in patients with CFS.

METHODS: Apoptosis was assessed in patients with CFS in conjunction with concentrations of the anti-inflammatory cytokine, transforming growth factor beta1 (TGFbeta1).

RESULTS: The 47 patients with CFS had higher numbers of apoptotic neutrophils, lower numbers of viable neutrophils, increased annexin V binding, and increased expression of the death receptor, tumour necrosis factor receptor-I, on their neutrophils than did the 34 healthy controls. Patients with CFS also had raised concentrations of active TGFbeta1 (p < 0.005).

CONCLUSIONS: These findings provide new evidence that patients with CFS have an underlying detectable abnormality in their immune cells.

 

Source: Kennedy G, Spence V, Underwood C, Belch JJ. Increased neutrophil apoptosis in chronic fatigue syndrome. J Clin Pathol. 2004 Aug;57(8):891-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770396/ (Full article)