: J Transl Med. 2006 Aug 15;4:34. Links
Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data.
a.. Vermeulen RC,
b.. Scholte HR.
CFS and Pain Research Center Amsterdam, Waalstraat 25-31, 1078 BR Amsterdam, The Netherlands. rv@cvscentrum.nl.

ABSTRACT: BACKGROUND: CFS is a clinical state with defined symptoms, but undefined cause. The patients may show a chronic state of immune activation and treatment with an antibiotic in this subgroup has been suggested. METHODS: In a retrospective study, the response of CFS patients to azithromycin, an antibiotic and immunomodulating drug, has been scored from the patients records and compared with clinical and laboratory data. Azithromycin was not the first choice therapy, but offered when the effect of counseling and L-carnitine was considered insufficient by the patient and the clinician. RESULTS: Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine. CONCLUSION: The efficacy of azithromycin in the responsive patients could be explained by the modulating effect on a chronic primed state of the immune cells of the brain, or the activated peripheral immune system. Their lower acetylcarnitine levels may reflect a decreased antioxidant defense and/or an increased consumption of acetylcarnitine caused by oxidative stress.

PMID: 16911783 [PubMed - in process]

1: J Autoimmun. 2006 Oct 27; [Epub ahead of print] Links
Fibromyalgia, infection and vaccination: Two more parts in the etiological puzzle.
a.. Ablin JN,
b.. Shoenfeld Y,
c.. Buskila D.
Department of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizman St., 64239 Tel-Aviv, Israel.

As the pathogenesis of fibromyalgia continues to raise debate, multiple putative triggers have been implicated. The current review summarizes the available data linking fibromyalgia to either infection or vaccination. Multiple infectious agents have been associated with the development of either full-blown fibromyalgia (e.g. hepatits C), or with symptom complexes extensively overlapping with that syndrome (e.g. chronic Lyme disease). The cases of Lyme disease, mycoplasma, hepatits C and HIV are detailed. Despite the described associations, no evidence is available demonstrating the utility of antibiotic or anti-viral treatment in the management of fibromyalgia. Possible mechanistic links between fibromyalgia and HIV are reviewed. Associations have been described between various vaccinations and symptom complexes including fibromyalgia and chronic fatigue syndrome. The case of Gulf War syndrome, a functional multisystem entity sharing many clinical characteristics with fibromyalgia is discussed, with emphasis on the possibility of association with administration of multiple vaccinations during deployment in the Persian Gulf and the interaction with stress and trauma. Based on this example a model is proposed, wherein vaccinations function as co-triggers for the development of functional disorders including fibromyalgia, in conjunction with additional contributing factors.

PMID: 17071055 [PubMed - as supplied by publisher]

1: J Affect Disord. 2006 Sep 26; [Epub ahead of print] Links
Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability.
a.. Maes M,
b.. Mihaylova I,
c.. Leunis JC.
MCare4U Outpatient Clinics, Belgium; Department of Psychiatry, Vanderbilt University Nashville, TN, USA.

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls. We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.

PMID: 17007934 [PubMed - as supplied by publisher]

1: J Clin Virol. 2006 Nov;37(3):139-50. Epub 2006 Sep 15. Links
Chronic fatigue syndrome.
a.. Devanur LD,
b.. Kerr JR.
Chronic Fatigue Syndrome (CFS) Group, Department of Cellular & Molecular Medicine, St. George's University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.

Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host aspects) and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising environmental aspects). Emotional stress appears to be very important as it reduces the ability of the immune system to clear infections, it's presence has been shown to determine whether or not an individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But, emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS. There is no specific treatment for CFS other than the much underutilised approach of specific treatment of virus infections. Current priorities are to understand the molecular pathogenesis of disease in terms of human and virus gene expression, to develop a diagnostic test based on protein biomarkers, and to develop specific curative treatments.

PMID: 16978917 [PubMed - in process]

1: Soc Work Health Care. 2006;43(4):85-98. Links
Iraqi Gulf War Veteran Refugees in the U.S.:PTSD and Physical Symptoms.
a.. Jamil H,
b.. Nassar-McMillan SC,
c.. Salman WA,
d.. Tahar M,
e.. Jamil LH.
, 15400 W McNichols, 2nd Floor, Detroit, MI, hjamil@med.wayne.edu.

Veterans of the Gulf War present various symptoms and maladies. Reports by governmental and private entities have yielded mixed results and have been fraught with criticisms of biased research design. The vast majority of these studies have focused on U.S. veterans, with a much smaller number focusing upon British veterans. Very few have examined Iraqi Gulf War veterans. Our study involves administering a health issues questionnaire to a sample of Iraqi Gulf War veteran refugees in the U.S. Results indicate relationships between Post-Traumatic Stress Disorder (PTSD) scores and health outcome measures of chronic fatigue, fibromyalgia, functional status, quality of life, and health care utilization in terms of frequency and level of intensity. Implications for further inquiry are presented.

PMID: 16966311 [PubMed - in process]

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.
a.. Hickie I,
b.. Davenport T,
c.. Wakefield D,
d.. Vollmer-Conna U,
e.. Cameron B,
f.. Vernon SD,
g.. Reeves WC,
h.. Lloyd A;
i.. Dubbo Infection Outcomes Study Group.
Brain and Mind Research Institute, Sydney University, Sydney, NSW 2050, Australia.

OBJECTIVE: To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections. DESIGN: Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis). SETTING: The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104,400 residents. PARTICIPANTS: 253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. OUTCOME MEASURES: Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups. RESULTS: Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors. CONCLUSIONS: A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.

PMID: 16950834 [PubMed - indexed for MEDLINE]

1: J Clin Pathol. 2006 Aug 25; [Epub ahead of print] Links

Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome).
a.. Puri BK.
Hammersmith Hospital, United Kingdom.

Evidence is put forward to suggest that myalgic encephalomyelitis, also known as chronic fatigue syndrome, may be associated with persistent viral infection. In turn, such infections are likely to impair the ability of the body to biosynthesize n-3 and n-6 long-chain polyunsaturated fatty acids by inhibiting the delta-6 desaturation of the precursor essential fatty acids alpha-linolenic acid and linoleic acid. In turn, this would impair the proper functioning of cell membranes, including cell signalling, and have an adverse effect of the biosynthesis of eicosanoids from the long-chain polyunsaturated fatty acids dihomo-a-linolenic acid, arachidonic acid and eicosapentaenoic acid. These actions might offer an explanation for some of the symptoms and signs of myalgic encephalomyelitis. A potential therapeutic avenue may be offered by bypassing the inhibition of the enzyme delta-6-desaturase by administering both virgin cold-pressed non-raffinated evening primrose oil and eicosapentaenoic acid. The former would supply gamma-linolenic acid and lipophilic pentacyclic triterpenes. The gamma-linolenic acid can readily be converted into dihomo-a-linolenic acid and thence arachidonic acid, while triterpenes have important free radical scavenging, cyclooxygenase and neutrophil elastase inhibitory activities. Furthermore, both arachidonic acid and eicosapentaenoic acid are, at relatively low concentrations, directly virucidal.

PMID: 16935966 [PubMed - as supplied by publisher]

1: Clin Chim Acta. 2006 Jul 14; [Epub ahead of print] Links
beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome.
a.. Hannestad U,
b.. Theodorsson E,
c.. Evengard B.
Faculty of Health Science, Division of Clinical Chemistry, Linkoping University, SE-581 85 Linkoping, Sweden.

BACKGROUND: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of gamma-aminobutyric acid (GABA) and/or its structural analogue beta-alanine in the urine from CFS patients. Both GABA and beta-alanine are inhibitory neurotransmitters in the mammalian central nervous system. METHODS: The 24 h urine excretion of GABA and beta-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale. RESULTS: Men had a significantly higher excretion of both beta-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither beta-alanine nor GABA. No correlation was found between the excretion of beta-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of beta-alanine in their 24 h urine samples than control subjects. CONCLUSIONS: Increased excretion of beta-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and beta-alanine in some CFS patients.

PMID: 16934791 [PubMed - as supplied by publisher]

1: Environ Health Perspect. 2006 Oct;114(10):1553-7. Links
Persistence of symptoms in veterans of the First Gulf War: 5-year follow-up.
a.. Ozakinci G,
b.. Hallman WK,
c.. Kipen HM.
Bute Medical School, University of St. Andrews, St. Andrews, Fife, Scotland, United Kingdom.

BACKGROUND: During the 1990-1991 Gulf War, approximately 700,000 U.S. troops were deployed to the Persian Gulf theater of operations. Of that number, approximately 100,000 have presented medical complaints through various registry and examination programs. OBJECTIVES: Widespread symptomatic illness without defining physical features has been reported among veterans of the 1991 Gulf War. We ascertained changes in symptom status between an initial 1995 symptom evaluation and a follow-up in 2000. METHODS: We assessed mailed symptom survey questionnaires for 390 previously surveyed members of the U.S. Department of Veterans Affairs Gulf War Registry for changes over the 5-year interval in terms of number and severity of symptoms. RESULTS: For the cohort as a whole, we found no significant changes in symptom number or severity. Those initially more symptomatic in 1995 showed some improvement over time, but remained much more highly symptomatic than those who had lesser initial symptomatology. CONCLUSIONS: The symptom outbreak following the 1991 Gulf War has not abated over time in registry veterans, suggesting substantial need for better understanding and care for these veterans.

PMID: 17035142 [PubMed - in process]


1: Psychoneuroendocrinology. 2006 Oct 14; [Epub ahead of print] Links
Enhanced cortisol suppression to dexamethasone associated with Gulf War deployment.
a.. Golier JA,
b.. Schmeidler J,
c.. Legge J,
d.. Yehuda R.
Department of Psychiatry, James J Peters VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA; Mount Sinai School of Medicine, New York, USA.

OBJECTIVE: To examine whether PTSD or post-deployment health symptoms in veterans of the first Gulf War (Operation Desert Shield/Storm) are associated with enhanced suppression of the pituitary-adrenal axis to low-dose dexamethasone (DEX). METHOD: Plasma cortisol and lymphocyte glucocorticoid receptor (GR) number were measured at 08:00h on two consecutive days, before and after administration of 0.5mg of DEX at 23:00h in 42 male Gulf War veterans (14 without psychiatric illness, 16 with PTSD only, and 12 with both PTSD and MDD) and 12 healthy male veterans not deployed to the Gulf War or another war zone. RESULTS: In the absence of group differences in basal cortisol levels or GR number, Gulf War veterans without psychiatric illness and Gulf War veterans with PTSD only had significantly greater cortisol suppression to DEX than non-deployed veterans and Gulf War veterans with both PTSD and MDD. Gulf War deployment was associated with significantly greater cortisol suppression to DEX controlling for weight, smoking status, PTSD, and MDD; PTSD was not associated with response to DEX. Among Gulf War veterans musculoskeletal symptoms were significantly associated with cortisol suppression and those who reported taking anti-nerve gas pills (i.e., pyridostigmine bromide) during the war had significantly greater DEX-induced cortisol suppression than those who did not. CONCLUSIONS: The data demonstrate that alterations in neuroendocrine function are associated with deployment to the Gulf War and post-deployment musculoskeletal symptoms, but not PTSD. Additional studies are needed to examine the relationship of enhanced glucocorticoid responsivity to deployment exposures and chronic unexplained medical symptoms in Gulf War veterans.

PMID: 17049422 [PubMed - as supplied by publisher]


1: Philos Trans R Soc Lond B Biol Sci. 2006 Apr 29;361(1468):681-7. Links
Immunological dysfunction, vaccination and Gulf War illness.
a.. Peakman M,
b.. Skowera A,
c.. Hotopf M.
Department of Immunobiology, King's College London, School of Medicine at Guy's, UK.

One candidate cause of Gulf War illness is vaccination against infectious diseases including medical counter-measures against biological weapons. One influential theory has suggested that such mass-vaccination caused a shift in immune response to a Type 2 cytokine pattern (Th2), which it was suggested was accompanied by a chronic fatigue syndrome-like illness. This article critically appraises this theory. We start by examining epidemiological evidence, which indicates that single vaccines are unlikely to be a substantial cause of Gulf War illness, but that there was a modest relationship with multiple vaccines, which was strongest in those vaccinated while deployed to the Gulf. These relationships may be affected by recall bias. We conclude by examining the results of immunological studies carried out in veterans or in a relevant setting in vitro. The balance of evidence from immunological studies on veterans returning from the War, including those developing multi-symptom illness, is that the immune response has not become polarized towards Th2. In summary, the epidemiological evidence for a multiple vaccine effect on Gulf War-related illness remains a potentially important aetiological lead, but mechanistic studies available at this stage do not identify any immunological basis for it.

PMID: 16687270 [PubMed - indexed for MEDLINE]

4: Hunt SC, Jakupcak M, McFall M, Orsborn M, Felker B, Larson S, Klevens M. Related Articles, Links
[Unable to display image] Re: "Chronic multisymptom illness complex in Gulf War I veterans 10 years later".
Am J Epidemiol. 2006 Oct 1;164(7):708-9; author reply 709-10. Epub 2006 Aug 30. No abstract available.
PMID: 16943267 [PubMed - indexed for MEDLINE]

1: Med Mycol. 2006 Nov;44(7):585-90. Links
Fatigue in coccidioidomycosis. Quantification and correlation with clinical, immunological, and nutritional factors.
a.. Muir Bowers J,
b.. Mourani JP,
c.. Ampel NM.
Valley Fever Center for Excellence and the Department of Medicine of the University of Arizona, and the Southern Arizona Veterans Affairs Health Center System, Tucson, Arizona, USA.

While described in the past, the frequency and degree of fatigue associated with symptomatic coccidioidomycosis has never been quantified. Using the Fatigue Severity Scale (FSS), severe fatigue (FSS score = 41) was found in 65% of cases of active coccidioidomycosis compared to 42% in cohort of control subjects with chronic medical diseases (P=0.024). Fatigue in patients with symptomatic coccidioidomycosis declined significantly over four months (P=0.023). Severe fatigue in patients with symptomatic coccidioidomycosis was significantly associated with low body mass index (BMI; P=0.024) but was not significantly associated with either serum leptin (r2=0.078, P=0.261) or serum TNF-alpha (r2=0.028, P=0.504) concentrations. Severe fatigue is a common condition among patients with active coccidioidomycosis and is associated with declining BMI.

PMID: 17071551 [PubMed - in process]