Tag: Enlander

Response to Derek Enlander

Sir,

Derek Enlander’s comments refer to Table 4 in our paper1 which describes the association of baseline characteristics with change in physical function at follow-up. It does not describe the outcome which can be found in Table 2. This shows an improvement in fatigue (−6.8; 95% CI −7.4 to −6.2; P < 0.001), physical function (4.4, 95% CI 3.0 to 5.8; P < 0.001), anxiety, depression and pain at follow-up.

In addition, as we state in the methods, the scores from the different inventories were re-scaled, so that a regression coefficient of 1 represents a 10% change in the score. Hence, the coefficient of −0.47 (95% CI −0.58 to −0.36) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) Chalder Fatigue score at baseline, indicates that each 10% increment in baseline Chalder Fatigue (i.e. 3.3 points on the original 0 to 33 scale) is associated with a mean change of −4.7 points (95% CI −5.8 to −3.6 points) on the original 0 to 100 SF-36 scale at follow-up. Similarly, the coefficient of 0.81 (95% CI 0.75 to 0.87) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) SF-36 score at baseline, indicates that each 10% increment in baseline physical function (i.e. 10 points on the original 0 to 100 SF-36 scale) is associated with a mean change of 8.1 points (95% CI 7.5 to 8.7 points) on the original 0 to 100 SF-36 scale at follow-up.

In summary, our paper shows that patients showed improvements in fatigue, physical disability, anxiety, depression and pain. Table 4 referred to by Derek Enlander show that worse fatigue and disability at assessment predict a worse outcome for disability at follow-up.

You can read the rest of this comment here: https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander

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Source: Crawley E. Response to Derek Enlander. QJM. 2014 Mar;107(3):247. doi: 10.1093/qjmed/hct171. Epub 2013 Aug 22. https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander (Full article)

 

 

RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study

Sir,

In a very impressive paper1 embracing a large cohort (834) of ME CFS (myalgic encephalomyelitis, Chronic fatigue syndrome) patients selected by the Fukuda criteria, we can see in Table 4 the associations and changes of baseline characteristics with physical function at follow-up in the Chalder Fatigue scale −0.47 (−0.58 to −0.36) and in the SF-36 (physical function phase) 0.81 (0.75 to 0.87). This perhaps represents approximately an 8% change after the PACE recommended GET/CBT therapy after a variable number of months of therapy. This shows a relatively insignificant improvement. Do we presume that the authors therefore are not emphatically encouraging the PACE recommendation of GET/CBT as a means of primary treatment of ME CFS?

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Source: Enlander D. RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study. QJM. 2014 Jan;107(1):87. doi: 10.1093/qjmed/hct169. Epub 2013 Aug 22. https://academic.oup.com/qjmed/article/107/1/87/1513843/RE-Treatment-outcome-in-adults-with-chronic

 

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a neuro-immune disease of uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not show any significant differences between CFS/ME and controls.

In this study, we analysed parvovirus B19 markers in CFS/ME patients (n=200), diagnosed according to Fukuda CDC criteria, and normal blood donors (n=200). Serum from each subject was tested for anti-B19 VP2 IgM and IgG (by Biotrin ELISA), anti-B19 NS1 IgM and IgG (by immunofluorescence), and B19 DNA (by real-time PCR).

CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (chi(2)=64.8; P<0.0001; odds ratio=9.42, CI 5.11-17.38). Of these 83 patients, 61 complained of chronic joint pain, while 22 did not.

Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (chi(2)=9.35, P<0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient.

 

Source: Kerr JR, Gough J, Richards SC, Main J, Enlander D, McCreary M, Komaroff AL, Chia JK. Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Gen Virol. 2010 Apr;91(Pt 4):893-7. doi: 10.1099/vir.0.017590-0. Epub 2009 Dec 9. https://www.ncbi.nlm.nih.gov/pubmed/20007355

 

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes.

AIM: To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection.

METHODS: Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q-fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors.

RESULTS: In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors’ previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein-Barr virus and enterovirus, the two most common infectious triggers of CFS/ME.

CONCLUSIONS: This study confirms the involvement of these genes in CFS/ME.

 

Source: Zhang L, Gough J, Christmas D, Mattey DL, Richards SC, Main J, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010 Feb;63(2):156-64. doi: 10.1136/jcp.2009.072561. Epub 2009 Dec 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921262/ (Full article)

 

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction.

Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

 

Source: Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J,Enlander D, Nutt DJ, Holgate ST. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis. 2008 Apr 15;197(8):1171-84. doi: 10.1086/533453.  http://jid.oxfordjournals.org/content/197/8/1171.long (Full article)

 

Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX

Abstract:

Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology. These similarities in the literature suggested the exploration of lipids in sera of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which is typically used for screening ciguateric ocean fish. Sera from patients with other diseases, including hepatitis B, cancer, and diabetes, were included to assess the degree of specificity involved.

Sera were treated with acetone in a ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted acetone fraction of the 37 normal showed +/- activity to +activity with 16 no titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40 titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer, 50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or =1:40 titer.

Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These data are summarized in Fig. 1. As shown in Table 1, a significant increase (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal group. A preliminary chemical study in C18 octadecylsilyl columns showed all fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol, and 100% methanol) to contain lipids reactive to MAb-CTX with different intensities. Prostaglandins were shown in 100% methanol fraction.

Competitive MIA with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope suggested similarities in structure with ciguatoxin. This was compatible with the neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1, chloroform : methanol solvents.

Copyright 2003 John Wiley & Sons, Ltd.

 

Source: Hokama Y, Uto GA, Palafox NA, Enlander D, Jordan E, Cocchetto A. Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX. J Clin Lab Anal. 2003;17(4):132-9. http://www.ncbi.nlm.nih.gov/pubmed/12784262