Tag: 2003

Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Alterations of the immune-neuroendocrine interplay have been described in chronic fatigue syndrome (CFS). Employing a recently developed method, the study set out to investigate whether patients with CFS have an altered sensitivity to glucocorticoids (GCs) when under stress.

METHODS: A total of 21 CFS patients and 20 healthy age- and gender-matched controls underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). Salivary and plasma cortisol levels were measured repeatedly following exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNC-α).

RESULTS: Cortisol responses following the TSST did not differ significantly between CFS patients and healthy controls. GC sensitivity differed significantly between CFS patients and healthy controls, with CFS patients showing a greater sensitivity towards GCs (TNF-α: F 1/39 = 7.32, P = 0.01; IL-6: F 1/39 = 9.73, P = 0.004).

CONCLUSION: Consistent with recent evidence, CFS patients are characterized by an enhanced sensitivity to glucocorticoids. The implications for secondary processes, such as the regulatory influence of glucocorticoids on immune processes, are discussed.

 

Source: Gaab J, Rohleder N, Heitz V, Schad T, Engert V, Schürmeyer TH, Ehlert U. Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome. Acta Neuropsychiatr. 2003 Aug;15(4):184-91. doi: 10.1034/j.1601-5215.2003.00033.x. http://www.ncbi.nlm.nih.gov/pubmed/26983566

 

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms

Abstract:

Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans.

Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive).

Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant.

Severity and incidence of patients’ signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

 

Source: Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May;111(5):557-66. http://www.ncbi.nlm.nih.gov/pubmed/12887507

 

Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review

Abstract:

OBJECTIVE: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior.

METHODS: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study.

RESULTS: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

CONCLUSIONS: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as “common mental disorders” does not seem fully appropriate.

 

Source: Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003 Jul-Aug;65(4):528-33. http://www.ncbi.nlm.nih.gov/pubmed/12883101

 

Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities. Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both.

In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals, significantly less than in patients.

Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS.

It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

 

Source: Endresen GK. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatol Int. 2003 Sep;23(5):211-5. Epub 2003 Jul 16. http://www.ncbi.nlm.nih.gov/pubmed/12879275

 

One-year outcome of unexplained fatigue syndromes in primary care: results from an international study

Abstract:

BACKGROUND: Outcome studies of chronic fatigue, neurasthenia and other unexplained fatigue syndromes are few and have been carried out in developed Western countries. This paper aimed to study the outcome of unexplained fatigue syndromes in an international primary care sample and to identify risk factors for persistence.

METHOD: We used data from the WHO collaborative study of psychological problems in general health care, in which 3201 primary care attenders from 14 countries were followed-up for 12 months. The assessment included a modified version of the Composite International Diagnostic Interview.

RESULTS: Unexplained fatigue persisted in one-fifth to one-third of the subjects depending on the definition of fatigue. From the factors studied only severity of fatigue and psychiatric morbidity at baseline were associated with persistence 12 months later. Outcome did not differ between countries of different stages of economic development.

CONCLUSIONS: The prognosis of fatigue syndromes in international primary care is relatively good. The study underlines the importance of psychological factors in influencing short-term prognosis.

 

Source: Skapinakis P, Lewis G, Mavreas V. One-year outcome of unexplained fatigue syndromes in primary care: results from an international study. Psychol Med. 2003 Jul;33(5):857-66. http://www.ncbi.nlm.nih.gov/pubmed/12877400

 

Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients

Abstract:

Protein carbonyl levels, a measure of protein oxidation, were found to be significantly elevated (p < 0.0005) in the sera of chronic fatigue syndrome (CFS) patients vs. controls. In contrast, the total protein levels in sera CFS patients were unchanged from those of controls. The elevated protein carbonyl levels confirm earlier reports suggesting that oxidative stress is associated with chronic fatigue syndrome and are consistent with a prediction of the elevated nitric oxide/peroxynitrite theory of chronic fatigue syndrome and related conditions.

 

Source: Smirnova IV, Pall ML. Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Mol Cell Biochem. 2003 Jun;248(1-2):93-5. http://www.ncbi.nlm.nih.gov/pubmed/12870659

 

Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence and incidence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources and for practicing physicians when examining and caring for patients.

METHODS: We conducted a random digit-dialing survey and clinical examination to estimate the prevalence of CFS in the general population of Wichita, Kan, and a 1-year follow-up telephone interview and clinical examination to estimate the incidence of CFS. The survey included 33 997 households representing 90 316 residents. This report focuses on 7162 respondents aged 18 to 69 years. Fatigued (n = 3528) and randomly selected nonfatigued (n = 3634) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. The clinical examination included the Diagnostic Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, laboratory testing, and a physical examination.

RESULTS: The overall weighted point prevalence of CFS, adjusted for nonresponse, was 235 per 100,000 persons (95% confidence interval, 142-327 per 100,000 persons). The prevalence of CFS was higher among women, 373 per 100,000 persons (95% confidence interval, 210-536 per 100,000 persons), than among men, 83 per 100,000 persons (95% confidence interval, 15-150 per 100,000 persons). Among subjects nonfatigued and fatigued for less than 6 months, the 1-year incidence of CFS was 180 per 100,000 persons (95% confidence interval, 0-466 per 100,000 persons).

CONCLUSIONS: Chronic fatigue syndrome constitutes a major public health problem. Longitudinal follow-up of this cohort will be used to further evaluate the natural history of this illness.

 

Source: Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003 Jul 14;163(13):1530-6. http://www.ncbi.nlm.nih.gov/pubmed/12860574

 

Diagnosing chronic fatigue syndrome: comparison of a protocol and computerised questionnaires

Abstract:

BACKGROUND: In the context of outpatient care and within the framework of scientific research, guidelines and measuring instruments have been developed to help improve CFS diagnostics. The purpose of this study was to measure the agreement between the evaluations of chronically fatigued patients by physicians using a CFS protocol and by researchers using computerised questionnaires.

METHODS: The sample consisted of 516 patients referred to an internal medicine outpatient clinic with complaints of chronic fatigue. Retrospectively the medical records and the computerised questionnaires were checked separately and compared to see whether the criteria for diagnosis of CFS had been met. In addition, the reasons for not diagnosing CFS were evaluated.

RESULTS: Agreement between the physicians’ and the researchers’ evaluations was 84%. Disagreement mostly concerned severity of fatigue and functional impairment, or premorbid exclusion criteria. A physical cause for the chronic fatigue was only found in 3% of the cases.

CONCLUSIONS: For physicians, questionnaire assessment may be complementary to the CFS protocol in optimising the process of diagnosing CFS.

 

Source: Prins JB, Elving LD, Koning H, Bleijenberg G, van der Meer JW. Diagnosing chronic fatigue syndrome: comparison of a protocol and computerised questionnaires. Neth J Med. 2003 Apr;61(4):120-6. http://www.ncbi.nlm.nih.gov/pubmed/12852720

 

Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome

Abstract:

The disturbance of the central nervous system and immunological abnormalities have been suggested in patients with chronic fatigue syndrome(CFS). We focused on immunological abnormalities against neurotransmitter receptors in CFS.

Using a sensitive radioligand assay, we examined serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1), mu-opioid receptor (OPRM1), 5-hydroxytryptamine receptor 1A (HTR1A), and dopamine receptor D2 (DRD2) in patients with CFS (n=60) and results were compared with those in patients with autoimmune disease (n=33) and in healthy controls (n=30).

The mean anti-CHRM1 antibody index was significantly higher in patients with CFS (p<0.0001) and autoimmune disease (p<0.05) than that in healthy controls, and positive reaction was found in 53.3% of patients with CFS. Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. Anti-nuclear antibodies were found in 56.7% (34/60) of patients with CFS, but anti-nuclear antibody titers did not correlate with the activities of the above four autoantibodies.

The patients with positive autoantibodies to CHRM1 had a significantly higher mean score (1.81) of ‘feeling of muscle weakness’ than negative patients (1.18) among CFS patients (p<0.01). Higher scores on ‘painful node’, ‘forgetfulness’, and ‘difficulty thinking’ were also found in CFS patients with anti-CHRM1 antibodies but did not reach statistical significance.

In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms. Our findings suggested that subgroups of CFS are associated with autoimmune abnormalities of CHRM1.

 

Source: Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N. Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med. 2003 Aug;12(2):225-30. http://www.ncbi.nlm.nih.gov/pubmed/12851722

 

Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions

Abstract:

This chapter reviews our current knowledge on the presence of overlapping syndromes in one form of chronic diffuse pain, fibromyalgia. Patients with fibromyalgia often present with signs and symptoms of other unexplained clinical conditions, including chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, and multiple chemical sensitivities. The high prevalence, impact on function and opportunities for treatment underscore the need for clinicians and researchers to screen routinely for co-morbid unexplained clinical conditions among persons with fibromyalgia. We, therefore, describe a simple approach to screening for such conditions in accordance with published criteria. Interventions should directly address both fibromyalgia symptoms and co-morbid unexplained clinical conditions, as well as the multiple factors that propagate pain, fatigue and limitations in function.

 

Source: Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol. 2003 Aug;17(4):563-74. http://www.ncbi.nlm.nih.gov/pubmed/12849712