Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome

Abstract:

PURPOSE: To establish an inexpensive, simple method of predicting peak oxygen uptake (VO2peak) in patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CFS).

DESIGN: A retrospective observational study.

SETTING: An outpatient tertiary care chronic fatigue clinic.

SUBJECTS: Two hundred and forty consecutive patients fulfilling the 1994 CDC criteria for CFS.

INTERVENTIONS: Heart rate, metabolic and ventilatory parameters were measured continuously during a maximal exercise stress test on a bicycle ergometer. Using the equation peak oxygen uptake = 13.1 x peak workload +284 (used by Mullis et al., Br J Sports Med 1999; 33: 352-56), VO2peak was predicted from the peak workload of a maximal exercise capacity test. Pearson correlation coefficient and linear regression analysis were used to establish the most accurate way to predict VO2peak.

RESULTS: Percentage error encountered when comparing actual measured VO2peak with predicted value was 17.3% (+/-10.0). A strong correlation between VO2peak and peak workload was observed (r= 0.89, p < 0.001). A regression analysis established the relation as VO2peak = 10.47 x peak workload +284.1, where VO2peak is given in ml/min and peak workload in W (error in prediction = 11.0+/-9.5%).

CONCLUSIONS: Monitoring of the peak workload during a maximal, graded bicycle ergometric test suffices to predict the VO2peak. When predicting VO2peak the used operational definition for the diagnosis of CFS could be taken into account. Compared with the equation used by Mullis et al., peak workload is multiplied by 10.47 in order to predict peak oxygen uptake in CDC-defined CFS patients.

 

Source: Nijs J, De Meirleir K. Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome. Clin Rehabil. 2004 Nov;18(7):785-92. http://www.ncbi.nlm.nih.gov/pubmed/15573835

 

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism

Abstract:

Chronic fatigue syndrome (CFS) is characterized by idiopathic fatigue of greater than 6 months’ duration with postexertional exacerbation and many other symptoms. A trend toward relative hypocortisolism is described in CFS. Twin and family studies indicate a substantial genetic etiologic component to CFS. Recently, severe corticosteroid-binding globulin (CBG) gene mutations have been associated with CFS in isolated kindreds. Human leukocyte elastase, an enzyme important in CBG catabolism at inflammatory sites, is reported to be elevated in CFS. We hypothesized that CBG gene polymorphisms may act as a genetic risk factor for CFS.

A total of 248 patients with CFS defined by Centers for Disease Control criteria, and 248 controls were recruited. Sequencing and restriction enzyme testing of the CBG gene coding region allowed detection of severe CBG gene mutations and a common exon 3 polymorphism (c.825G–>T, Ala-Ser224).

Plasma CBG levels were measured in 125 CFS patients and 198 controls by radioimmunoassay. Total and free (calculated and measured) cortisol levels were ascertained in single samples between 8-10 a.m. The age of onset (mid 30s) and gender ratio (2.2:1, female:male) of the patients were similar to those reported in U.S. epidemiologic studies.

A trend toward a preponderance of serine224 homozygosity among the CFS patients was noted, compared with controls (chi2 = 5.31, P = 0.07). Immunoreactive-CBG (IR-CBG) levels were higher in Serine/Alanine (Ser/Ala) than Ala/Ala subjects and higher again in Ser/Ser subjects, this effect was strongest in controls; Ser/Ser: 46.1+/-1.8 (n = 31, P = 0.03) vs. Ser/Ala: 42.4+/-1.0 (n = 56, P = 0.05) vs. Ala/Ala: 40.8+/-1.7 microg/mL (n = 21). Despite higher CBG levels, there was a nonsignificant trend toward lower total and free plasma cortisol in serine allele positive patients, total cortisol: Ser/Ser: 13.3+/-1.4 (n = 34) vs. Ser/Ala: 14.0+/-0.7 (n = 66) vs. Ala/Ala: 15.4+/-1.0 (n = 23).

Homozygosity for the serine allele of the CBG gene may predispose to CFS, perhaps due to an effect on hypothalamic-pituitary-adrenal axis function related to altered CBG-cortisol transport function or immune-cortisol interactions.

 

Source: Torpy DJ, Bachmann AW, Gartside M, Grice JE, Harris JM, Clifton P, Easteal S, Jackson RV, Whitworth JA. Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism. Endocr Res. 2004 Aug;30(3):417-29. http://www.ncbi.nlm.nih.gov/pubmed/15554358

 

Exhaustion–not fatigue

Erlend Hem & Jon Håvard Loge refutes the language gap in this Journal no. 18/2004 our argument that “chronic  exhaustion syndrome” should be the Norwegian term for “chronic fatigue syndrome” ( 1 , 2 ). In his speech, they write that “many patients with somatic diseases and fatigue would probably feel somewhat alien to mention symptom as fatigue, because fatigue usually linked to a prior activity” ( 2 ).

You can read the rest of this comment here: http://tidsskriftet.no/article/1095666

 

Source: Wyller VB, Wyller TB. Exhaustion–not fatigue. Tidsskr Nor Laegeforen. 2004 Nov 4;124(21):2802; author reply 2802. [Article in Norwegian] http://tidsskriftet.no/article/1095666 (Full article)

 

Factors influencing the diagnosis of chronic fatigue syndrome

Abstract:

BACKGROUND: Most of what is believed about chronic fatigue syndrome (CFS) is based on clinic-based studies. These studies may not reflect CFS cases in the population.

METHODS: We used data from a population-based study of CFS to identify factors associated with receiving a CFS diagnosis. Wichita, Kan, residents were screened by random-digit dialing. Eligible individuals completed a telephone interview. Respondents meeting CFS criteria were invited for a clinical evaluation to confirm CFS. We analyzed all persons with confirmed CFS. The main outcomes of this study, prevalence and incidence of CFS, are published elsewhere. Herein, we present an exploratory analysis with previous CFS diagnosis as the outcome, predicted by demographic and symptom characteristics.

RESULTS: We confirmed CFS in 90 subjects; 14 (16%) had been previously diagnosed as having CFS. Persons in the middle- vs the higher-income group were more likely to have been diagnosed as having CFS (9 [29%] of 31 subjects vs 3 [8%] of 39 subjects; P = .03), as were those with sudden vs gradual fatigue onset (7 [41%] of 17 subjects vs 4 [6%] of 64 subjects; P < .01), those reporting tender lymph nodes (7 [33%] of 21 subjects vs 7 [10%] of 69 subjects; P = .02), and those reporting a sore throat (6 [35%] of 17 subjects vs 8 [11%] of 73 subjects; P = .02). Only 17 (21%) of 81 subjects had sudden fatigue onset, and tender lymph nodes (reported in 21 [23%] of 90 subjects) and a sore throat (reported in 17 [19%] of 90 subjects) were the least common symptoms.

CONCLUSION: Most cases of CFS in the population are unrecognized by the medical community; persons diagnosed as having CFS may be different from persons with CFS in the general population.

 

Source: Solomon L, Reeves WC. Factors influencing the diagnosis of chronic fatigue syndrome. Arch Intern Med. 2004 Nov 8;164(20):2241-5. http://www.ncbi.nlm.nih.gov/pubmed/15534161

 

Perceived stigma in functional somatic syndromes and comparable medical conditions

Abstract:

OBJECTIVE: To determine if patients with functional somatic syndromes (FSS) perceive greater levels of stigma than patients with comparable medical conditions that have a clear medical pathology.

METHODS: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), or irritable bowel syndrome (IBS) were compared to multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBS), respectively.

RESULTS: There were greater levels of perceived stigma in the combined group of FSS compared to the medical control group. When each FSS was compared to its matched control group, only CFS had a higher level of perceived stigma. These results remained when controlling for other variables relevant to stigma.

CONCLUSIONS: The higher level of perceived stigma in CFS may be due to the ambiguity of its status as a medical condition. The absence of this effect in FM and IBS is consistent with a greater level of acceptance of these disorders as medical illnesses.

 

Source: Looper K, Kirmayer LJ. Perceived stigma in functional somatic syndromes and comparable medical conditions. J Psychosom Res. 2004 Oct;57(4):373-8. http://www.ncbi.nlm.nih.gov/pubmed/15518673

 

What causes chronic fatigue syndrome?

Comment in: Patients with chronic fatigue syndrome are being ignored. [BMJ. 2004]

Comment on: Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. [BMJ. 2004]

 

Chronic fatigue syndrome, also known as myalgic encephalomyelitis, is an illness of unknown nature and cause, but most medical authorities now accept its existence.1-3 Research about its cause has been hampered by the absence of a biological marker, the heterogeneous nature of the illness, and difficulties in differentiating cause from effect.2,3 Yet, some progress has been made, particularly when causes are divided into predisposing, triggering, and maintaining factors.

Women get chronic fatigue syndrome more commonly than men for unknown reasons, although increasing evidence suggests a genetic influence on the illness.1,3 Premorbid mood disorders are replicated risk markers for chronic fatigue syndrome;1,3 the risks may be inflated by shared symptoms or they may be markers for those patients with comorbid mood disorders.1,3-5 Another replicated premorbid risk marker is increased consulting of a doctor for minor illnesses up to 15 years before diagnosis,w1 w2 suggesting a general vulnerability for either ill health or seeking health care, the latter possibly being mediated by comorbid anxiety.4

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524091/

 

Source: White PD. What causes chronic fatigue syndrome? BMJ. 2004 Oct 23;329(7472):928-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524091/ (Full article)

 

Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome

Abstract:

We used differential-display PCR of peripheral blood mononuclear cells (PBMCs) to search for candidate biomarkers for chronic fatigue syndrome(CFS). PBMCs were collected from a subject with CFS and an age- and sex-matched control before and 24 h after exercise. RNA expression profiles were generated using 46 primer combinations, and the similarity between the individuals was striking.

Differentially expressed bands were excised, reamplified, and sequenced, yielding 95 nonredundant sequences, of which 50 matched to known gene transcripts, 38 matched to genes with unknown functions, and 7 had no similarity to any database entry. Most (86%) of the differences between the two subjects were present at baseline.

Differential expression of ten genes was verified by real-time reverse-transcription PCR: five (cystatin F, MHC class II, platelet factor 4, fetal brain expressed sequence tag, and perforin) were downregulated, and the remaining five genes (cathepsin B, DNA polymerase epsilon4, novel EST PBMC191MSt, heparanase precursor, and ORF2/L1 element) were upregulated in the subject with CFS. Many of these genes have known functions in defense and immunity, thus supporting prior suggestions of immune dysregulation in the pathogenesis of CFS.

Differential-display PCR is a powerful tool for identification of candidate biomarkers. Investigation of these markers in samples from well-designed epidemiological studies of CFS will be required to determine the validity of these candidate biomarkers. The real-time reverse-transcription PCR assays that we developed for assay of these biomarkers will facilitate high-throughput testing of these additional samples.

 

Source: Steinau M, Unger ER, Vernon SD, Jones JF, Rajeevan MS. Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome. J Mol Med (Berl). 2004 Nov;82(11):750-5. Epub 2004 Oct 14. http://www.ncbi.nlm.nih.gov/pubmed/15490094

 

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

Abstract:

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS).

CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice.

The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

 

Source: Wang XQ, Takahashi T, Zhu SJ, Moriya J, Saegusa S, Yamakawa J, Kusaka K, Itoh T, Kanda T. Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome. Evid Based Complement Alternat Med. 2004 Sep 1;1(2):203-206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC516453/ (Full article)

 

Neuropathology in rhinosinusitis

Abstract:

Pathophysiologic differences in neural responses to hypertonic saline (HTS) were investigated in subjects with acute sinusitis (n = 25), subjects with chronic fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing strengths of HTS were sprayed into their nostrils at 5-minute intervals. Sensations of nasal pain, blockage, and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons.

Urea and lysozyme secretion were dose dependent in all groups, suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only AR and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis, suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal provocations identified significant, unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome.

 

Source: Baraniuk JN, Petrie KN, Le U, Tai CF, Park YJ, Yuta A, Ali M, Vandenbussche CJ, Nelson B. Neuropathology in rhinosinusitis. Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11. Epub 2004 Oct 11. http://www.ncbi.nlm.nih.gov/pubmed/15477496