De claim van het Nijmeegs Kenniscentrum Chronische Vermoeidheid (NKCV)
op basis van een recent uitgevoerde studie [1]
dat XMRV (niet/nauwelijks) voorkomt onder ME/CVS-patiënten,
mist elke feitelijke onderbouwing.
Sterker, de kleine groep proefpersonen (n=32) in deze studie werden geselekteerd uit
een grotere groep "chronisch vermoeide, deels depressieve mensen"
die zichzelf rond 1994! diagnosticeerden en
aanmeldden bij het Nijmeegs Kenniscentrum Chronische Vermoeidheid [2, 3].
De populaties van de Nijmeegse studie,
"chronisch vermoeide, deels depressieve mensen",
en die van de oorspronkelijke Amerikaanse XMRV-studie uit Science [4, 5],
ME/CVS-patiënten die aan de Fukuda- en Canadese kriteria voldeden,
verschillen als dag en nacht.
Derhalve is de claim van het NKCV dat de oorspronkelijke XMRV-studie gerepliceerd werd
en dat XMRV niet/nauwelijks voorkomt onder ME/CVS-patiënten [1], volkomen onterecht.
Nog belangrijker is dat de onderzoekers die de 1994-groep hebben samengesteld
mensen die (vertraagd) herstelden van een virusinfekties hebben proberen uit te sluiten [2].
Dat betekent dat de Nijmeegse onderzoekers XMRV-infekties zochten
bij een groep mensen die bij voorkeur geen infekties onder de leden hadden (gehad)!
De Nijmeegse onderzoekers geven in hun studie zelf aan dat
de Erlwein/Wessely XMRV-studie [7] (ook) geen replicatiestudie was.
Kortom, de konklusie kan niet anders luiden dan dat de claims van de van Kuppeveld/NKCV-studie en de Engelse Erlwein/Wessely-studie op geen enkele wijze onderbouwd worden.
Deze rubriek bouwt voort op
Scandal in BMJ's XMRV/CFS Research/BMJ and XMRV Unplugged.
1. Patientenselektie van Kuppeveld
Een zeer kleine groep (n=32) [A]
- chronisch vermoeide [B],
- deels depressieve [C] mensen,
die geselekteerd werden uit een oorspronkelijke groep van 298 mensen [D],
- die zichzelf aangemeld hadden [E] en
- die zonder medische tussenkomst zichzelf diagnosticeerden [F],
waarbij
- mensen die (vertraagd) herstelden van een virale infektie [G] en
- mensen met symptomen die medisch verklaard zouden kunnen worden
(bijv. mensen die hartmedicatie gebruikten) [H]
zoveel mogelijk uitgesloten werden.
[A]
Citaat uit [1]:
In this study, we examined peripheral blood mononuclear cells of
all patients (n=32) and controls (n=43)
from whom original cryopreserved vials were still available.
This group included 25 patients and their matched controls,
as well as seven patients and 18 controls that were not matched to each other
[B]
Citaat uit [1]:
All patients of this cohort fulfilled the Oxford criteria and
reported severe, unexplained, debilitating fatigue of at least one year in duration. [6]
Citaat uit [2]:
... patients had to experience severe disabling fatigue, of definite onset,
lasting for more than 1 year; other symptoms may be present.
[C]
Citaat uit [2]:
Using a score of 16 or more, 36% of patients
[of the original cohort of 298 patients, FT]
could be considered as having a clinical depression.
[D]
Citaat uit [1]:
All patients and controls examined in this study were part of a Dutch cohort of 298 patients,
which has been described in detail. [2, 3]
All patients of this cohort fulfilled the Oxford criteria [6]
and reported severe, unexplained, debilitating fatigue of at least one year in duration.
[E]
Citaat uit [2]:
Three-hundred and ninety-five sell-referred patients were sent a postal questionnaire.
[F]
Citaat uit [2]:
Information on physical abnormalities and treatment relied on self-report.
This made the exclusion of patients with a medical condition known to produce fatigue difficult.
[G]
Citaat uit [2]:
To overcome this problem as far as possible, complaints had to have been present for more than 1 year.
This minimalized the risk of including patients with delayed convalescence of a viral infection.
[H]
Citaat uit [2]:
Respondents with definite or suspected illnesses that could provide an explanation for the complaints were excluded
(e.g. patients taking medication for heart problems).
2. Onterechte kritiek op Mikovits-studie
Citaat uit [1], studie NKCV:
Comparison with findings of previous studies
Unfortunately, the paper of Lombardi and colleagues lacked a clear description of their patient cohort.
Recently, at the Tri-Society Annual Conference 2009 in Lisbon,
a presentation reported that
the peripheral blood mononuclear cells were derived from
patients from the outbreak of chronic fatigue syndrome at Incline village
at the northern border of Lake Tahoe, United States (1984-5).
It seems unlikely that their study demonstrates
a viral association for sporadic chronic fatigue syndrome cases,
such as those we tested, or represents the majority of patients.
Citaat uit [5], Science-studie Mikovits e.a.:
Banked samples were selected for this study from patients
fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and
the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME)
and presenting with severe disability.
Samples were selected from several regions of the United States where outbreaks of CFS had been documented (S2).
These are patients that have been seen in private medical practices, and
their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities.
These included but were not limited to
perturbations of the 2-5A synthetase/RNase L antiviral pathway,
low natural killer cell cytotoxicity (as measured by standard diagnostic assays), and
elevated cytokines particularly interleukin-6 and interleukin-8.
In addition to these immunological abnormalities,
the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing.
The patients had been seen over a prolonged period of time and multiple longitudinal observations of the clinical and laboratory abnormalities had been documented.
Citaat uit informele toelichting Annette Whittemore (Facebook: klik hier)
All of the samples used in the Science study were donated to the WPI between 2006 and 2009
by physician diagnosed CFS patients based on the Fukuda and... Canadian Consensus definitions.
Patient samples were coded and randomly chosen from the WPI repository freezer.
Samples from this study are from CFS patients who come from all over the United States and many from around the world to be treated by CFS doctors.
3. Relevante opmerking t.a.v. Wessely XMRV-studie (klik hier)
Citaat uit [1]:
Comparison with findings of previous studies
Recently, a team from the United Kingdom reported the failure to detect XMRV
in all 186 tested peripheral blood mononuclear cell samples
from a well characterised cohort of British patients with chronic fatigue syndrome. [7]
This team,
however, did not use the same primer sets as used by Lombardi et al,
leaving open a possible explanation for the difference in results.
Referenties
- van Kuppeveld FJ,
Jong AS, Lanke KH, Verhaegh GW, Melchers WJ, Swanink CM, Bleijenberg G, Netea MG, Galama JM, van der Meer JW.
Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort.
BMJ. 2010 Feb 25;340:c1018v.
http://www.bmj.com/cgi/reprint/340/feb25_1/c1018.pdf
- Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G.
Dimensional assessment of chronic fatigue syndrome.
J Psychosom Res 1994;38:383-92.
http://dare.ubn.kun.nl/bitstream/2066/14900/1/4783.pdf
- Swanink CM, Vercoulen JH, Galama JM, Roos MT, Meyaard L, van der Ven-Jongekrijg J, et al.
Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.
J Infect Dis 1996;173:460-3.
http://www.ncbi.nlm.nih.gov/pubmed/8568312
- Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, et al.
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.
Science 23 October 2009;326:585-9. doi: 10.1126/science.1179052.
- Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, et al.
Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome.
Science 23 October 2009;326:585-9. doi: 10.1126/science.1179052.
Supporting Online Material: Materials and Methods, Figs. S1 to S6, Tables S1 and S2, and References).
http://www.sciencemag.org/cgi/data/1179052/DC1/1.
- Sharpe MC, Archard LC, Banatvala JE, Borysiewicz, LK, Clare AW, David A, Edwards RH, et al.
A report - chronic fatigue syndrome: guidelines for research.
J R Soc Med 1991;84:118-21.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/pdf/jrsocmed00127-0072.pdf
- Erlwein O, Kaye S,McClure M, Weber J, Wills G, Collier D, Wessely S, Cleare A.
Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome.
PLoS ONE 2010;5:e8519.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795199/pdf/pone.0008519.pdf.
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