20 February 2010

Topography of Scientific Inquiry, Part 2

It may be beneficial for some to have a look at the blog entry dated 7th January, 2010, which was a short analysis of the study published in PLoS, and the requirement, within scientific endeavor, to replicate studies.

This blog entry, once again, is an update and discussion around the latest research paper regarding the presence of XMRV in individuals with ME/CFS to come our of the UK. The aim is to provide factual information about the study and the response from the WPI, who first iderntified XMRV in relation to ME/CFS. The purpose is to generate discussions around this disease process, to further educate others and to continue to promote awareness of this disease process.

Please feel free to use any of the referenced information provided here to engage in these discussions in visible forums, as we work together towards ensuring our families, friends, communities, and medical professionals of this disease process and the desperate need for further research.

The study:

The UK study, conducted by Groom, H., et al (Retrovirology, 2010) aimed at looking for evidence of XMRV in two UK cohorts, and comparing them to controls. There were 170 samples collected from individuals with chronic fatigue syndrome, and 395 control samples from individuals without the disease. The research looked for evidence of XMRV in these samples by either identifying the presence of viral nucleic acids of XMRV, using PCR techniques, or by identifying serological responses in the samples, using a virus neutralisation assay (Groom, H., et al 2010).

First of all, the research looked for evidence of the viruses genetic code in the samples using PCR (Polymerase Chain Reaction). PCR is a method of amplifying a sequence of DNA and then looking for the specific genetic code of XMRV. (There's an simplified example of PCR at http://learn.genetics.utah.edu/content/labs/pcr/ which demonstrates this process in terms that even I can understand!) The research then looked for serological responses in the samples, evidence of XMRV antibodies, which would indicate that the immune system had been activated by XMRV, and had rallied up specific antibodies to fight the virus.

The results:

The results of the study undertaken by Groom, H., et al (2010) failed to identify XMRV by PCR methods in any of the samples.

26/565 samples tested positive for serological activity in response to XMRV, however, according to Groom, H., et al (2010), 25 of these samples were from individuals in the control group. This means only one individual who had a diagnosis of CFS demonstrated neutralising activity towards the virus XMRV. In other words, that sample had antibodies which could target XMRV.

I say 'could' because most of the 26 samples which tested positive for these antibodies, also demonstrated the ability to nutralise the virus particle if it was wrapped in an alternative viral protien coat. So, remembering that a virus is a length of viral DNA wrapped in a protien coat, when the researchers changed that usual protien coat on the virus to a protien coat from a different virus, the samples continued to show a neutralising serelogical response. This may indicate that another virus could have elicited these responses, and thus the antibodies residing in these samples were not necessarily responding to the XMRV.

There was detection of a serological response in 4 samples that was not elicited by a psuedotyped virus, meaning there were 4 samples which elicited a serological response to XMRV only


The conclusions drawn by this research was that there may be a danger in getting accrate results from serological surveys, because the antiviral response to XMRV may also be elicited by other viruses.

One reason why this was deflating for many individuals hoping to see positive results, is because of the involvement of Dr Jonathan Kerr. One of the researchers involved in this research paper, is Dr Jonathan R Kerr BSc, MBBCh, MD, PhD, FRCPath. Dr Jonothan Kerr received his medical qualification from Queens University of Balfast in 1987, and in 1995, he completed his qualifications at a microbiologist, has worked as a microbiologist in Balfast, Mnachester, and London, where, in 2001, he became the consultant senior lecturer in Microbiology at the Imperial College, and in 2005 became the Clinical Senior Lecturer in Inflammation at St Gorges University (IACFS/ME, 2010). Dr Jonathan Kerr worked on a study of parvovirus B19 infection, demonstrating a percentage of cases had developed 'CFS' which lasted for several years, and subsequently became interested in 'Chronic Fatigue Syndrome' (IACFS/ME 2020). IACFS/ME (2010) reports that "he is now the principal investigator in a programme of research on CFS", and is is interested in the genetics of "CFS", and potential relationship with microbial infections.

A discussion of the study:

Of the study, Kate Bishop, one of the researchers, stated "We are confident that, although we were unable to replicate the detection, our PCR assay is more sensitive than the earlier method and possessed the necessary sensitivity to detect XMRV had it been present" (Redorbit, 2010). However, this study fails to provide detail to allow interpretation of how many white blood cells were analyzed, and as a result, this may have impacted the results. The Whittemore Peterson Institue, (2010), have stated that "Insufficient number of cells analyzed may result in failure to detect a low copy virus like XMRV, regardless of the sensitivity of the assay'

The Whittemore Peterson Institute (2010) also stated a difference in collection, preparation and storage of DNA. Neither this UK study, or that published in PLoS, had any data on blood harvesting, storage, or quantity of isolated cells, and technologies used. The research paper published in Science had used "PCR on nucleic acids from both un-stimulated and stimulated white blood cells; XMRV protein expression from stimulated white blood cells; they completed virus isolation on the LNCaP cell line; and a specific antibody response to XMRV" (Whittemore Peterson Institute, 2010). Furthermore, the Whittemore Peterson Institue, (2010), 'When using PCR alone, the Science authors found that four samples needed to be taken at different times from the same patient in order for XMRV to be detected by PCR in freshly isolated white blood cells. More importantly, detection methods other than PCR showed that patients whose blood lacks sufficient amount of XMRV detectable by PCR are actually infected'.

In conclusion, this study is not a replication study. Realistically, a replication study requires the same environmental conditions and technologies are used. The Whittemore Peterson Institue, (2010) have stated that they have provided information and reagents to research groups in different areas to assist accurate replication studies to occur, however, neither this study, or the one published bu PLoS, 'requested positive control blood, plasma or nucleic acids'. This demonstrates that there is still a need for direct replication studies to take place before any concrete statements about the corrolation between ME/CFS and XMRV (causative or coexistant) can be made.


The Whittemore Peterson Institue (2010)., WPI is aware of the recent UK study that was unable to detect the presence of XMRV in any CFS patient samples. Retrieved Febuary 2010 from http://www.wpinstitute.org/news/news_current.html

IACFS/ME (2010)., IACFS/ME Board of Directors 2009. Retrieved Febuary 2010 from http://www.iacfsme.org/LeadershipoftheIACFSME/JonathanKerr/tabid/370/Default.aspx

Redorbit (2010)., Further Doubt Cast On Virus Link To Chronic Fatigue. Retrieved Febuary 2010 from http://www.redorbit.com/news/health/1823927/further_doubt_cast_on_virus_link_to_chronic_fatigue/

Groom, H., Boucherit, v., Makinson, K., Randal, E., Baptista, S., Hagan, S., Gow, H., Mattes, F., Breuer, J., Kerr, J., Stoye, J., Bishop, K. (2010) Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology 7:10. Retrieved Febuary 2010 from http://www.retrovirology.com/content/pdf/1742-4690-7-10.pdf

13 February 2010

Post exertional malaise

This is a revised blog entry.  There was some ambiguity identified in the previous post, which I have aimed to address.  Thank-you to each of those people who assisted with this, who have chosen not to identify themselves.  I am most grateful for your support and assistance.

Post exertional malaise is a familiar to many individuals with ME/CFS, and for those who have had this disease for several years or longer, it is likely to be a facet of the disease which is very disabling.  Some of us have learned to live within the confines of this symptom of ME/CFS, however it does pose many unseen limitations to how an individual may participate in their activities of daily living (housework, for example) personal activities of daily living (personal care).

Malaise is the term used by the Canadian Consensus Document to describe the onset of exacerbated signs and symptoms of ME/CFS, including cognitive function deterioration, and increased pain and fatigue. The term malaise is described in most literature as a vague feeling of general unwellness.   Encyclopedia.com states that malaise is a 'medical term for a general condition of unease, discomfort, or weakness' (Retrieved 10 February 2010), and the Oxford Nurses Dictionary, (4th ed.), defines malaise as 'the general feeling of being unwell. The feeling may be accompanied by a feeling of physical discomfort, and may indicate the presence of disease' (McFerran, 1998).

Individuals with ME/CFS identify this 'malaise' as the onset of exacerbated signs and symptoms of the disease, following a period of physical or mental exertion. For individuals with ME/CFS, it is common for this feeling to follow active physical exertion, such as going for a walk, hanging out the washing, cooking a meal, etc. Post exertional malaise typically lasts 24 hours or more following an activity or exercise.

For the purposes of this post, I will be using the word activity, and delineating it from the word exercise.  I will use the word 'activity' to describe the engagement of the body or the mind in tasks associated with daily living, as opposed to 'exercise'; the engagement of physical training to develop fitness and improve health.  I will not be addressing exercise or aerobic training.

There are physical signs associated with the symptom of post exertional malaise, which can be demonstrated by comparing an individual with ME/CFS with a healthy individual after participating in physical activity. An individual without ME/CFS will often experience anti depressant effect as a result of physical activity. This is caused by the increase of oxygen-carrying blood to the whereas individuals with ME/CFS show a decrease in oxygen and blood to the brain, which contributes to the feeling of malaise (van de Sande, 2009).  Individuals with ME/CFS demonstrate hypo-profusion of blood through particular areas of the brain, which means a decreased blood flow through the brain tissue, which is further decreased as a result of physical activity (van de Sande, 2009). This is the opposite of the effect of physical activity on the brain tissue of an individual who does not have ME/CFS (van de Sande, 2009). Body temperature normally increases with physical activity, however individuals with ME/CFS demonstrate a decreased body temperature after exercise (van de Sande, 2009).  A table of this can be found on page four of the Canadian Consensus document.

A further effect of the decrease of blood circulation in the brain is the decrease of the effect of endorphins on how an individual feels after exercise.  Endorphins are the body’s natural analgesics, (pain killers), which contribute to a increased sense of wellbeing in individuals without ME/CFS, after participating in physical exertion.

Although on average individuals with ME/CFS have an elevated resting heart rate, they typically demonstrate a significantly reduced heart rate when they are participating in an activity at their maximum workload. Individuals with ME/CFS also demonstrate 'an inability to reach the age-predicted target heart rates (van de Sande, 2009). Van de Sande, (2009), refers to a study completed by De Becker, et al (2000) which demonstrated that the maximum oxygen uptake and maximum workload attained by individuals with ME/CFS was approximately half that of sedentary controls. This could be attributed to autonomic dysfunction and/or heart dysfunction, which means that it is advisable for individuals who have ME/CFS not to try to attain age-predicted heart rates(van de Sande, 2009).  Other dysfunctions which are common for individuals with ME/CFS to experience after physical activity include impaired cognitive function, orthostatic intolerance and gait disturbance (van de Sande, 2009).

A dysfunction found in individuals with ME/CFS is Mitochondrial Myopathy.  The National Institute of Neurological Disease and Stroke define mitochondrial myopathy as a neuromuscular disease ‘caused by damage to the mitochondria—small, energy-producing structures that serve as the cells' "power plants” (May 2007).  Dr Cheney stated that in ME/CFS there is so much injury to the mitochondria that CFS could be called a mitochondrial disease (Seiverling, 2001).  This does not mean that the individual does not have ME/CFS, but that mitochondrial dysfunction plays a role in the disease pathology.  There is a link at the bottom of this blog entry which contains further information on mitochondrial myopathy, as discuss by Dr Cheney.

The following discussion on management techniques, which in some areas are used as part of generalized Cognitive Behaviour Therapeutic approaches.  This blog aims to discuss these techniques in isolation from any CBT intervention, as techniques which need to be carried out with care and support from a well educated medical team.  Again, the management techniques of pacing and grading will be discussed with regard to ADL’s and PADL’s, and not with reference to aerobic exercise programs.  Please use this for information and education purposes only, and do not embark on any physical exertion program without medical advice and support.

For individuals with ME/CFS, the subject of physical exertion can be a very sensitive and difficult one to address.  This is due to the nature of ME/CFS, where the disease is an exertional one (Lapp, 2006). There are small management techniques which individuals with ME/CFS may implement with support from a medical team, that can be used to help achieve activities.  Needless to say, this requires much forethought and planning. 

One of these managing techniques is grading.  Grading is the SLOW building up of tolerance to a realistic activity which has a predefined end point from the outset.  This end point is different for each individual.  The endpoint at which grading an activity stops, is the point at which participating in an activity can occur without ill effect, or post exertional malaise.  For example, an individual with ME/CFS might begin vacuuming for one minute every two days and build up to five or six minutes every two days before having a rest period. 
It is important to note that this is not a treatment technique, and does not lead to remission of ME/CFS signs and symptoms. Over four weeks, Black, et al (2005) found that  individuals with ME/CFS were able to increase their activity level, however, studies fatigue, muscle pain, and overall mood did not improve with increased activity. Black, et al., (2005) established from this that there is a limit to activity/exertion tolerance.  This means that an individual with ME/CFS may build up from a period of one minute to a period of six minutes of vacuuming over four weeks.  At six minutes on a good day, the activity is managed whilst still feeling a sense of wellbeing and absence of complete relapse, however this may remain the threshold, and any subsequent activity without a substantial rest period would tip the balance.

A good measure for a starting point of activity participation, is the amount of activity an individual with ME/CFS is able to tolerate on a bad day.  For some individuals, the extent of this may be getting out of bed and going to the bathroom and returning to bed for a rest.

Pacing of activity is another management strategies, where an activity, say hanging out the washing, is broken up into manageable chunks. An example may be hanging out three towels (the heaviest items) and having a break (for some people five minutes, for some people thirty minutes). The next would be hanging up two or three pairs of jeans, break, sweaters, break, then the socks, break, and underwear (lightest of the washing), so that as the activity proceeds, less and less exertion is required as the fatigue and ‘malaise’ sets in.

In the absence of being able to participate in an activity, i.e., for individuals who are bed bound, some techniques which may be beneficial include active and passive stretching of joints through range of motion.  Active stretching is the participation in a stretching activity independently; passive stretching requires that the individual is relaxed while someone moves each joint through a range of motion.  Even rolling over in bed is a form of stretching. 

In summary, individuals with ME/CFS should not view activity or exercise as a means by which they will recover.  Exercise done without support from properly educated medical professionals can be dangerous.  Instead, physical movement should be seen as an opportunity to avoid muscle atrophy and further weakness.  This means, once again, individuals with ME/CFS are in a position where they may need to take on a role of education within their medical teams.  I have included some resources below to assist with this.


Black, CD., O’Connor, PJ and McCully, KK. Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome. Dynamic Medicine, 2005, 4, 3. Retrieved February 2010 from  http://www.dynamic-med.com/content/pdf/1476-5918-4-3.pdf

Hoh, D, 2002.,  Retrieved February 2010 Treatment at the Cheney Clinic. http://www.prohealth.com/me-cfs/library/showarticle.cfm?id=3278&t=CFIDS_FM

Lapp, C (2006)., The Treatment of Chronic Fatigue Syndrome and Fibromyalgia Retrieved February 2010 from http://www.prohealth.com/library/showarticle.cfm?id=2926&t=CFIDS_FM

03 February 2010

ME/CFS and Pregnancy

ME/CFS and pregnancy

As with many of these blog entries, there is room for this to be added to, and it will be returned to from time to time, especially with advances in knowledge about XMRV, and it's potential contribution/co-morbidity to ME/CFS.

For many people, it is natural to grow up with aspirations of starting a family, and individuals with ME/CFS are no different in this respect.  Taking into consideration that roughly 60% of individuals with ME/CFS are female, and that the average onset of ME/CFS is within the typical childbearing age, it is essential that individuals with ME/CFS (and, of course, those supporting them) are well informed and well prepared before proceeding with a pregnancy.  Yes, pregnancy is a physical feat for the human body at the best of times, so there are added challenges to meet and overcome, but it is certainly possible.However, preparing for pregnancy for an individual with ME/CFS include many considerations which may not be issues for individuals without a ME/CFS diagnosis.

Up until this point, it has been suggested that there is no evidence of inheritance with ME/CFS, or that a diagnosis of ME/CFS in the mother would incur damage to the fetus. The recent findings of XMRV and it's potential contribution/co-morbidity to ME/CFS, however, XMRV is "thought to be transmitted through body fluids such as blood, semen, and mother’s breast milk but is not transmitted through the air". (Whittemore Peterson Institute). The Whittemore Peterson Institute recommends that individuals speak with their physician about XMRV and what safety measures might minimize possible transmission of this retrovirus. (2010).  It is integral to note at this stage that very little is currently known about XMRV, and as more is learned, knowledge and advice will be refined.  It is essential to stress that if you have concerns, talk to your physician.

The decision to raise children is one that needs to be made by both the mother and father, and is not one that can be made overnight.  There will be issues such as if the mother has ME/CFS, does she work, and if so, is it likely she will need to give up work early in the pregnancy? If the father has ME/CFS, how will he be able to support the mother during pregnancy? It is also wise to think in the medium term about whether it is likely one parent will be able to return to work, what needs to be addressed in terms of in-home maintenance (is it realistic to employ a cleaner), are there family and/or friends around who are able to help with some of the day to day tasks of family-hood? On the flip-side of this, not everything can be planned, some things will fall into place as and when they happen, and things will crop up that have not been considered.

In terms of preparing for pregnancy, including limiting alcohol and smoking, and getting a balanced diet, individuals with ME/CFS may also need to address any prescription medicines, herbal supplements or any other pharmacuticals they may be using.  This must be done in consultation with the appropriate medical professional, and individuals should not stop taking any medicines without medical advice. Some discussions may need to take place around risks some medications may pose during pregnancy, and what alternatives may be available, or weighing up the risks and benefits. It is also an idea to begin discussing things such as pain management during the pregnancy and especially during birth.

With regards to conception, some considerations need to be taken into account.  It is advised that some thought and planning goes into preparing to have sex, despite this sounding terribly unromantic!  Because sexual intercourse involves a high degree of physical exertion, it may be necessary to plan for a substantial time to rest afterwards.  Another issue to take into consideration is pain, and ensuring that the environment is set up to make things comfortable, with the use of pillows, cushions, and heating, ensuring the experience as enjoyable and pain free as possible.  It is also worth thinking about what time of day an individual experiences the least pain and fatigue, and also (with forethought to giving birth), what seasons are well/not well tolerated, knowing that it's realistic to experience a  'crash' after pregnancy.

During the first trimester of pregnancy, dramatic hormone changes can cause high levels of fatigue and nausea. For some mothers-to-be, this will pass as they enter into the second trimester, whereas for others, it may last the full term of pregnancy. By the third trimester, and especially in the final weeks of pregnancy, is often the hardest part of pregnancy. There are extra demands on the body from an increasingly growing baby, and extra weight to carry around, which all contributes to higher levels of fatigue.  It is important to rest as much as possible to help manage the physical fatigue, and prepare for giving birth.  It may be beneficial to participate in pre natal classes and get advice on relaxation techniques to help the process of giving birth.

When the time does (finally) arrive for birth, mothers with ME/CFS will tire quickly in labor, and may experience an increased level of pain. It is important that mothers with ME/CFS have access to adequate pain relief, and kept well hydrated.  'According to Dr. Bateman, stress and exhaustion cause the autonomic nervous system in a CFS patient to become more dysregulated and "almost chaotic," precipitating the likelihood of relapse. Bateman advises measures like maintaining vascular volume with intravenous fluid and pain and stress reduction techniques during childbirth to help prevent or moderate this response' (
Again, it is beneficial to know and discuss pain management options well in advance of labour and to have a plan (though realizing that in emergency situations, events may have to deviate from the plan in some cases).

It is common for a relapse of ME/CFS symptoms to occur post partum. 'Dr. Klimas observed that her patients with CFS typically do well postpartum until 3 to 6 months after delivery, at which time a relapse in CFS symptoms typically occurs, and is oftentimes severe. Dr. Klimas hypothesizes that relapse at this time may be related to physiologic reduction in red cell mass and blood volume that increased in pregnancy, and/or to the cumulative stress of interrupted sleep and demands of caring for an infant' (2007, retrieved from http://www.medscape.com/viewarticle/576986_6).  As with all ME/CFS relapses, early planning can help prepare the family for this occurrence. There are many practical steps which can be made to help minimize energy expenditure for individuals with ME/CFS caring for newborns and adjusting to a new addition to the family.  These may include setting up the nursery with as many things in one place as possible, such as warm water in a thermos, and having a nappy bucket just outside the door, to minimize walking distance.  If the house is two storied, have a changing table set up on both floors, and use a stool or chair when doing nappy changes, and have a comfortable chair next to the baby cot/bassinet for feeding times. Please feel free to comment or add to this post.


Lapp C. Childbearing and CFIDS: Making a difficult decision. The CFIDS Chronicle. 2000;Summer.


Retrieved on 03/02/2010 from http://www.medscape.com/viewarticle/576986_6

Retrieved on 03/02/2010 from http://www.mecfsparents.org.uk/Pregnancy.htm

Retrieved on 03/02/2010 from http://www.zimbio.com/Fibromyalgia/articles/13/Sex+Chronic+Fatigue+Syndrome