Tag: 2003

Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects

Abstract:

A reduced secretion of cortisol has been proposed as a possible explanation of the symptoms in chronic fatigue syndrome. However, the evidence of hypocortisolism in chronic fatigue syndrome is conflicting.

In order to simultaneously assess possible alterations in adrenocortical sensitivity and secretory adrenal reserve, the authors administered both low-dose and high-dose ACTH to a group of 18 chronic fatigue syndrome patients and 18 age- and gender-matched healthy comparison subjects.

No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.

 

Source: Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer T, Ehlert U. Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects. Psychosomatics. 2003 Mar-Apr;44(2):113-9. http://www.ncbi.nlm.nih.gov/pubmed/12618533

 

AIDS and CFS/ME: a tale of two syndromes

Abstract:

Both HIV/AIDS and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) presented major challenges for medicine, science and society. This article explores what could have impeded investigation of–and specifically pharmaceutical engagement with–CFS/ME, in contrast to the impressive achievements seen in HIV/AIDS. It explores the obstruction of mind-body dualism in a historical context, and examines some of the possible obstacles to pharmaceutical enquiry. Nothing of real substance is identified that would justify the lack of investment and interest in solutions for patients with CFS/ME.

Comment in: AIDS and CFS/ME. [Clin Med (Lond). 2003]

 

Source: Pinching AJ. AIDS and CFS/ME: a tale of two syndromes. Clin Med (Lond). 2003 Jan-Feb;3(1):78-82. http://www.ncbi.nlm.nih.gov/pubmed/12617422

 

Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue

Abstract:

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-alpha/beta) pathway in CFS resulting in a sustained upregulation of 2(‘),5(‘)-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-alpha/beta usually complain of severe fatigue as a limiting side effect.

Beside the 2-5OAS, IFN-alpha/beta induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains.

From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function.

 

Source: Englebienne P, Verhas M, Herst CV, De Meirleir K. Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: possible etiology for unexplained chronic fatigue. Med Hypotheses. 2003 Feb;60(2):175-80. http://www.ncbi.nlm.nih.gov/pubmed/12606231

 

Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome

Abstract:

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.

 

Source: Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM. Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Neuroreport. 2003 Feb 10;14(2):225-8. http://www.ncbi.nlm.nih.gov/pubmed/12598734

 

Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome

Abstract:

Acute primary Q fever is followed by various chronic sequelae. These include subacute Q fever endocarditis, granulomatous reactions in various organs or a prolonged debilitating post-infection fatigue syndrome (QFS). The causative organism, Coxiella burnetii, persists after an initial infection. The differing chronic outcomes may reflect variations within cytokine and accessory immune control genes which affect regulation of the level of persistence. As a preliminary test of the concept we have genotyped QFS patients and controls for gene variants spanning 15 genes and also examined HLA-B and DR frequencies. QFS patients exhibited a significantly increased frequency of HLA-DR-11 compared with controls and also significant differences in allelic variant frequencies within the NRAMP, and IFN gamma genes. These results indicate a possible genetic role in the expression of overt chronic Q fever. Further studies will be undertaken to increase sample sizes, to survey other forms of chronic Q fever and to examine Q fever patients who have recovered without sequelae.

 

Source: Helbig KJ, Heatley SL, Harris RJ, Mullighan CG, Bardy PG, Marmion BP. Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome. Genes Immun. 2003 Jan;4(1):82-5. http://www.ncbi.nlm.nih.gov/pubmed/12595908

 

Diverse etiologies for chronic fatigue syndrome

Comment on: Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. [Clin Infect Dis. 2002]

 

SIR—Koelle et al.  recently studied 22 pairs of identical twins discordant for chronic fatigue syndrome and concluded that there was no major contribution for viral infections in the perpetuation of chronic fatigue syndrome (CFS). The authors should be commended for their methodology and the use of well-matched control subjects. However, the study raised several issues.

First, similar to previous studies, the approach of Koelle et al.  was to look for statistical differences among the well-matched pairs with respect to the presence of viral antibodies and, more specifically, the presence of DNA of the viruses studied. Although these viruses were no more prevalent among the patients with CFS than among their healthy twins, one cannot conclude that these viruses are not the cause of CFS in a small subset of patients. CFS has been described in a small number of patients who had had well-documented acute Epstein-Barr virus (EBV), cytomegalovirus (CMV), and parvovirus B19 infections, and many of the patients responded to specific antiviral therapy. Of the first 200 patients with CFS who we evaluated for viral etiologies , only ∼10% had etiologies that were attributed to the viruses studied by Koelle et al. Chlamydia pneumoniae infection, an uncommon, although treatable, cause of CFS, was also dismissed in a previous, smaller study .

You can read the rest of this comment here: http://cid.oxfordjournals.org/content/36/5/671.long

 

Source: Chia JK, Chia A. Diverse etiologies for chronic fatigue syndrome. Clin Infect Dis. 2003 Mar 1;36(5):671-2; author reply 672-3. http://cid.oxfordjournals.org/content/36/5/671.long (Full article)

 

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome

Abstract:

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress.

METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD.

RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002).

CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

 

Source: Razumovsky AY, DeBusk K, Calkins H, Snader S, Lucas KE, Vyas P, Hanley DF, Rowe PC. Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome. J Neuroimaging. 2003 Jan;13(1):57-67. http://www.ncbi.nlm.nih.gov/pubmed/12593133

 

Blood flow and muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and oxidative delivery to skeletal muscle. Patients with CFS according to CDC (Center for Disease Control) criteria ( n =19) were compared with normal sedentary subjects ( n =11). Muscle blood flow was measured with Doppler ultrasound after cuff ischaemia and exercise. Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemic oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous wavelength near-IR spectroscopy. Muscle metabolism was measured using (31)P magnetic resonance spectroscopy. CFS patients and controls were not different in the peak blood flow after cuff ischaemia, the rate of recovery of phosphocreatine after submaximal exercise, and the rate of recovery of oxygen saturation after cuff ischaemia. In conclusion, CFS patients showed no deficit in blood flow or oxidative metabolism. This suggests that CFS symptoms do not require abnormal peripheral function.

 

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Blood flow and muscle metabolism in chronic fatigue syndrome.  Clin Sci (Lond). 2003 Jun;104(6):641-7. http://www.ncbi.nlm.nih.gov/pubmed/12589704

 

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome

Abstract:

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a ‘haemodynamic instability score’ (HIS).

AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS.

DESIGN:  Prospective controlled study.

METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT.

RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%.

DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician’s diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Comment in:

The head-up tilt test for diagnosing chronic fatigue syndrome. [QJM. 2003]

Assessing chronic fatigue. [QJM. 2003]

 

Source: Naschitz JE, Rosner I, Rozenbaum M, Naschitz S, Musafia-Priselac R, Shaviv N, Fields M, Isseroff H, Zuckerman E, Yeshurun D, Sabo E. The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.  QJM. 2003 Feb;96(2):133-42. http://qjmed.oxfordjournals.org/content/96/2/133.long (Full article)

 

Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time

Abstract:

Methods used for the assessment of cardiovascular reactivity are flawed by nonlinear dynamics of the cardiovascular responses to stimuli. In an attempt to address this issue, we utilized a short postural challenge, recorded beat-to-beat heart rate (HR) and pulse transit time (PTT), assessed the data by fractal and recurrence quantification analysis, and processed the obtained variables by multivariate statistics. A 10-min supine phase of the head-up tilt test was followed by recording 600 cardiac cycles on tilt, that is, 5-10 min.

Three groups of patients were studied, each including 20 subjects matched for age and gender–healthy subjects, patients with essential hypertension (HT), and patients with chronic fatigue syndrome (CFS). The latter group was studied on account of the well-known dysautonomia of CFS patients, which served as contrast against the cardiovascular reactivity of the healthy population. A total of 52 variables of the HR and PTT were determined in each subject.

The multivariate model identified the best predictors for the assessment of reactivity of healthy subjects vs CFS. Based on these predictors, the “Fractal & Recurrence Analysis-based Score” (FRAS) was calculated: FRAS=76.2+0.04*HR-supine-DET -12.9*HR-tilt-R/L -0.31*HR-tilt-s.d. -19.27*PTT-tilt-R/L -9.42*PTT-tilt-WAVE. The median values and IQR of FRAS in the groups were: healthy=-1.85 (IQR 1.89), hypertensives=+0.52 (IQR 5.78), and CFS=-24.2 (5.34) (HT vs healthy subjects: P=0.0036; HT vs CFS: P<0.0001). Since the FRAS differed significantly between the three groups, it appears likely that the FRAS may recognize phenotypes of cardiovascular reactivity.

 

Source: Naschitz JE, Rosner I, Shaviv N, Khorshidi I, Sundick S, Isseroff H, Fields M, Priselac RM, Yeshurun D, Sabo E.Erratum in: J Hum Hypertens. 2003 Aug;17(8):585. Itzhak, R [corrected to Rosner, I]. Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time. J Hum Hypertens. 2003 Feb;17(2):111-8. http://www.ncbi.nlm.nih.gov/pubmed/12574789