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Evaluating Blood Volume Studies - Some Thoughts David S. Bell, MD, FAAP Published in Lyndonville News, March 2000
‘I. Blood Volume Data. So far in our office we have measured the circulating blood volume in nearly fifty patients using the Chromium 51 method. It is essential that this method be employed (done in the nuclear medicine department of large University hospitals) as it is the only reliable method of assessing blood volume. There are two components of blood: the red blood cells and the plasma (fluid); everything else doesn't contribute much to the volume. The results are expressed as a function of body weight. Normal red blood cell mass should be between 23 and 28 ml/Kg, and the plasma volume should be between 40 and 52 ml/Kg. The total circulating blood volume is the sum of the two parts, and should lie between 60 and 80 ml/K.
Overall, about eighty percent of our patients with CFS have had either a low red blood cell mass, plasma volume, or both. Some patients have been extremely low, less than 50% of normal blood volume. To put this in perspective, if a healthy person were to bleed 40% of their volume out in a car accident it would likely be fatal. The loss in CFS is presumably gradual. The finding of decreased blood volume in CFS first came from Dr. David Streeten, and I am convinced it is accurate and will serve as a marker for the illness in some regard.’
One Doctor Speaks Out Against the Morbid Fascination with Psychiatric Morbidity with Regard to Chronic Fatigue Syndrome and Fibromyalgia Alan Gurwitt, M.D.
Every so often there is an upsurge of debate about the place of psychological problems in regard to CFS, FM, and ME. As a psychiatrist who has been seeing patients with these illnesses since 1986, as well as following the literature closely, I have often been embarrassed by and angry at many of my colleagues who fall in line with self-declared "experts" who see somatization everywhere.
Ever since the mid-1980's, there have been "researchers" with an uncanny knack for cornering research funds because of their already-formed biases that are in synch with the biases of the funding government organizations, who declare CFS, FM, ME to have a psychological basis or, more recently and insidiously, avoiding specificity about etiology, indicate that CBT and graded exercise will do the therapeutic job, thus in part implying a major psychological causative factor.
I have noticed the following deficits in their work, their thinking, their word choices-or should I say-choice of terms, and their research methods…..
Can hysteria be diagnosed with confidence? by Dr Elizabeth Dowsett [A review of the latest research]
"This comprehensive review, mainly of the work done by Professor Behan’s team in Glasgow begins with EPIDEMIOLOGY which, it is pointed out, has become a numbers game depending upon which ever ‘CFS’ definition is in vogue, and that the disease, in endemic or epidemic form, presents with a ‘flu like respiratory or gastrointestinal illness in 80% of cases’. A very thorough and detailed account is then given of symptoms, laboratory and other investigations. Despite some minor inconsistencies with previous advise, the review is especially valuable for this section and for its 89 references to world literature."
PROOF POSITIVE? Evidence of the deliberate creation via social constructionism of "psychosocial" illness by cult indoctrination of State agencies, and the impact of this on social and welfare policy By Eileen Marshall and Margaret Williams, 30th August 2005
The ME community has for years urged UK Government bodies to fund research into both the epidemiology and the biomedical abnormalities that are known to exist in myalgic encephalomyelitis (ME, also listed as Chronic Fatigue Syndrome by the World Health Organisation in the International Classification of Diseases as Chronic Fatigue Syndrome (CFS) as a disorder of the nervous system), almost always to no avail, to the extent that the ME community realised that there were powerful vested interests at stake which were known to involve a group of psychiatrists known as the "Wessely School". Now, it seems, there is hard evidence of the reason for the Establishment's apparent resistance to acknowledge ME/CFS as an organic disorder and, as previously realised, it does indeed involve psychiatrists of the "Wessely School".
The evidence is contained in a book entitled "Biopsychosocial Medicine: An integrated approach to understanding illness" edited by psychiatrist Peter White, Professor of Psychological Medicine at St Bartholomew's and the London, Queen Mary School of Medicine recently published by Oxford University Press (2005).
This provides a most illuminating exposition of what had long been suspected; the list of contributors is itself equally confirmatory.
…Unless the disease itself is robustly investigated and understood -- and ultimately treated -- no amount of psychosocial 'management' will have worthwhile or lasting effects, either upon the hapless sufferer trying to cope without medical support with serious and destructive organic pathology or upon the cash-strapped and rapidly sinking NHS.
A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Yamamoto Y, LaManca JJ, Natelson BH.
‘The specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.’
The Montague/Hooper Paper by Sally Montague and Professor Malcolm Hooper, 2001
Full title: CONCERNS ABOUT THE FORTHCOMING UK CHIEF MEDICAL OFFICER’S REPORT ON MYALGIC ENCEPHALOMYELITIS (ME) AND CHRONIC FATIGUE SYNDROME (CFS), NOTABLY THE INTENTION TO ADVISE CLINICIANS THAT ONLY LIMITED INVESTIGATIONS ARE NECESSARY
In our opinion, when taken in consideration of all that is already known about the biomarkers of ME/CFS, the evidence of serious pathology presented at Seattle emphasises the unacceptability of advising that such pathology should not be fully investigated. It also underlines the fallaciousness of advising that such substantial pathology can be satisfactorily treated by cognitive behavioural therapy or graded exercise; thus we believe it is imperative for people to be aware that the most influential members of the CMO’s Working Group are apparently still determined to proceed along such avenues despite all the evidence which has been put before them.
[Includes a summary of much of the medical research into ME]
CONCEPTS OF ACCOUNTABILITY? by Professor Malcolm Hooper and The Hooper Team, 2001
This present document should be read in conjunction with the amended original Montague / Hooper paper
The release of the original Montague/Hooper document brought forth poignant worldwide gratitude from researchers and patients alike; it also brought forth an immediate barrage of letters which essentially amounted to a threatening campaign against the authors; these letters were written almost entirely by Dr Charles Shepherd, Medical Director of the UK ME Association and member of the CMO’s Key Group charged with preparing the forthcoming report, whose membership of HealthWatch was mentioned by Montague and Hooper in their paper. On his own written admission Dr Shepherd caused the Chairman of HealthWatch (solicitor Malcolm Brahams of Messrs David Wineman, Craven House, 121 Kingsway, London WC2B 6NX) to send official letters to Professor Hooper.
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Disturbingly, the prime authors of the UK Chief Medical Officer’s report on CFS/ME are apparently determined to equate ME with "CFS" as one single entity, which they refer to as "CFS/ME" (see below). To do so takes no account of the different interpretations of the undifferentiated term "CFS" and it is likely to perpetuate the existing confusion to the detriment of those with non-Oxford defined CFS. It is already known that the CMO’s Report on CFS/ME will recommend psychiatric management approaches: such approaches may be appropriate when considering the Oxford definition of CFS but may be harmful when considering the international interpretation of "CFS" which more closely equates with ME.
Montague and Hooper believe that by seeking to equate one specific syndrome or subgroup with another syndrome or subgroup which does not have the same features, the CMO’s Working Group may be doing a grave disservice to both patients and medical science: they believe it is scientifically unacceptable that one name should refer to two different case definitions, each of which having different symptom profiles. Montague and Hooper are concerned at the repeated refusal by the CMO’s Key Group to acknowledge the clinical difference between ME and other forms of CFS, a difference which many believe has important implications for management and treatment outcomes, as well as for service provision.
[A solid overview of the medical and political facts surrounding M.E. and CFS in the UK.]
Exercise a health risk for chronic fatigue [syndrome] sufferers
Adelaide scientists have found evidence that exercise programs commonly undertaken by patients with chronic fatigue syndrome (CFS), may actually make the condition worse.
On the pathophysiology of ME/CFS by Les Simpson, MD
The significance of the concept of 'mean capillary diameter' is that it explains why individuals with similar values for altered red cell shapes do or do not evince symptoms. While the effects on red cell shape of a change in the environment is the same, only those with small capillaries will develop symptoms. As overexertion changes red cell shape in an additive fashion, there will be an accompanying exacerbation of symptoms. It is worth noting that in a CFS patient with SPECT-demonstrated reduced cerebral blood flow in a pre-exercise sample, the cerebral blood flow was further reduced in a post-exercise SPECT scan.
Medical Neurobiology of CFS & FM: May May 7-9, 1993 by Jay Goldstein
It is widely documented that exercise is an exacerbator of CFIDS symptoms. Drs. Mena and Goldstein presented a series of SPECT scans which showed extreme hypoperfusion (reduced blood flow) in the brain following exercise. There appeared to be "holes" where blood would normally be flowing -- the degree of hypoperfusion was astonishing. Even 24 hours later, cerebral blood flow was severely reduced.
Cerebral hypoperfusion is not the only result of exercise intolerance. Drs. Lapp and Goldstein referenced irregular tidal volume rates common in PWCs. Hyperventilation and shallow breathing are frequent results of exertion. Normal controls breathe irregularly at the start of exercise, but respiration becomes regular over time. Dr. Lapp reported that PWCs breathed more regularly than controls at the outset, but during exercise their breathing was more variable. Dr. Goldstein concurred, "This phenomenon has never been described before in any population and, as of now anyway, we think that it's a diagnostic marker for CFS."
Neuroendocrine responses were often reversed or blunted in the Cheney-Lapp study. Cortisol, epinephrine, norepinephrine, DHEA levels and body temperature normally rise with exercise, but PWCs were found to have lower than expected measures of all of the above. Dr. Goldstein related this phenomenon to limbic dysfunction, as altered levels of interleukins and nitric oxide (NO) can result in altered neuroendocrine responses to exercise.
Dr. Lapp and Dr. Kathy Sietsema reported that PWCs reached anaerobic threshold much sooner than predicted. Anaerobic threshold (AT) is the point at which a healthy person becomes completely fatigued and cannot exercise any longer (commonly called "hitting the wall"). In the Cheney-Lapp study, PWCs continued exercising beyond the point of AT. Dr. Cheney has hypothesized that PWCs normally perform above AT in everyday activity due to a metabolic injury, and therefore are more accustomed to performing at this level than controls.
Dr. Les Simpson – Rethinking the Pathogenesis of CFIDS By Craig Maupin at http:///www.cfidsreport.com
Simpson continues, "I found that ME blood filtered poorly - implying that they had a problem with blood flow, particularly at capillary level. In a paper published by New Jersey Medicine, I suggested that ME people might have the anatomical feature of smaller than usual capillary diameters. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people."
Tricky Heart May Cause ME/CFS Abnormal Heart Pumping After Exercise Linked to Chronic Fatigue Syndrome
Peckerman's research team at the VA Medical Center in East Orange, N.J., used a sophisticated test to measure how well the heart pumps blood. They gave the test to 16 chronic fatigue syndrome patients, both before and after they exercised. They also tested four non-athletic volunteers. All of the patients' and volunteers' hearts' pumped normally during rest. After exercise, however, 13 of the 16 chronic fatigue patients' hearts pumped less blood than they did at rest.
"Basically we are talking about heart failure," Peckerman tells WebMD. "But chronic fatigue syndrome is a progressive disease. If we were able to detect this in its early stages, it is quite possible there might be a way to treat it."
Emory University cardiologist Joseph I. Miller III, MD, says Peckerman's findings on a potential cause of chronic fatigue syndrome are very interesting. He agrees that these patients have serious heart problems. "Typically we see this in people with three-vessel heart disease," Miller tells WebMD. "A drop in [blood pumped by the heart] during exercise is not a typical response. It is actually a marker of significant coronary artery obstruction."
What's happening to the hearts of people with chronic fatigue syndrome? It's too soon to tell, but Peckerman has a theory. "There is some indication that chronic fatigue syndrome is precipitated by a viral infection," he says. "Some of the viruses that have been suspected have an affinity for the heart."
Dr Paul Cheney on heart issues and ME/ICD-CFS
"Now, do CFIDS patients prefer to stand up or lie down? Of course, they prefer to lie down. Do you know why? "Do you know what your cardiac output does when you stand up? It drops 30%. In all humans, without exception. So very critical to this technology is that it's the only one that could be done upright [again, four positions on the tilt table are best; standing up and laying down at a minimum]. And what they found is absolutely astonishing, truly astonishing. When [disabled CFIDS patients] stand up, [they're] on the edge of organ failure due to low cardiac output."
The Peckerman article Dr. Cheney refers to is available free online.
"Peckerman's research team at the VA Medical Center in East Orange, N.J., used a sophisticated test to measure how well the heart pumps blood. They gave the test to 16 chronic fatigue syndrome patients, both before and after they exercised. They also tested four non-athletic volunteers. All of the patients' and volunteers' hearts' pumped normally during rest. After exercise, however, 13 of the 16 chronic fatigue [syndrome] patients' hearts pumped less blood than they did at rest.
"Basically we are talking about heart failure," Peckerman tells WebMD. "But chronic fatigue syndrome is a progressive disease. If we were able to detect this in its early stages, it is quite possible there might be a way to treat it."
Simpson feels impaired blood flow offers a unifying thesis that can explain many of these distinct symptoms. He vividly recalls the unique response to exercise of a patient referred to him. "Two scans were done [SPECT scans] -- pre and post exercise. While the pre-exercise scan showed reduced cerebral blood flow, this was much worse in the post-exercise scan. At that time, the effects of physical activity on red cell shape had not been reported. This shows the extent of ignoring blood rheology factors as determinants of blood flow."
What is it About Psychiatry? By Gurli Bagnall, 12 July 2005.
"[Psychiatry] is a field where fads and fancies flourish. Hardly a year passes without some new claim, [But]The early promises of each of these discoveries are uniformly unfulfilled." (US) Joint Commission on Mental Illness and Mental Health, 1961
What is it was about the medical profession and psychiatry in particular, that attracts the sort of person who will deliberately put a seriously ill child into a swimming pool and stand watching as he drowns. The expert who knew best, who would brook no argument, and who insisted the childs weakness would disappear once he ran out of breath, was wrong. Had the boy fully clothed mother not jumped in to save him, he would have drowned
[Response to Wessely on Co-cure I would like to thank Professor Simon Wessely for his interest in my piece entitled "What is it About Psychiatry?". It is heart warming to note that, as Director of King's Centre for Military Health Research, he is taking such a keen interest in children with ME.
However, I feel I must point out that the title he gave his response ("Libelling Paediatricians"), is misleading. According to the Collins Concise Dictionary, libel means "the publication of defamatory matter" and it can only be defamatory if it is not true.]
09-08-2004 In Dr. Lapp's words:
This Cochrane review study is a sore subject! I obtained a copy of the entire review, and it is just horrible. The author examined 9 studies, accepted only 5, and none were from the USA. Here are some of the problems: 1. Fatigue was the main outcome measured; depression and quality of life were secondary outcome measurements. 2. Fukuda international criteria for Chronic Fatigue Syndrome (CFS) were used in only two studies, and it appears that the subjects were not terribly ill. 3. In two of the studies (Fulcher and Appleby), 80-92% of subjects were working at the time of the study; in Powell's study 35% were working. The others did not report. Obviously this was not a very sick cohort. 4. Of the 5 studies, the Appleby study was the only one with a rigorous exercise plan (70-75% of aerobic capacity for 30 minutes). This study did NOT show any improvement in subjects, and had the highest dropout rate. The 4 other studies used a low level of exercise (40% of aerobic capacity). 5. The so-called "experts' [plural] that were listed were Dr. Peter White [only], whom I believe works closely with Wessley and Sharpe. Read biased. 6. Even though the authors concluded "patients with CFS who are similar to those in the trials should be offered exercise therapy," the press did not make it clear that these CFS patients were rather high functioning, and that most CFS patients could not tolerate such exercise. 7. The authors also concluded from this same cohort that "exercise therapy may not worsen outcomes on average." This is very misleading since it is part of the Fukuda definition that exercise causes post-exertional malaise, and all Persons with Chronic Fatigue Syndrome (PWCs) may trigger prolonged relapses if they overexert. Sadly, this Cochrane review study once again sends the incorrect message to primary physicians -- that they should exercise all PWCs and not worry about post-exertional sequelae.
Charles W. Lapp, M.D. HUNTER-HOPKINS CENTER, P.A.
Exercise responsive genes measured in peripheral blood of women with Chronic Fatigue Syndrome and matched control subjects. Whistler T, Jones JF, Unger ER, Vernon SD.Journal: BMC Physiol. 2005 Mar 24;5(1):5 PMID: 15790422
‘Exercise-responsive genes differed between CFS cases and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport activity/ion channel activity were evident at baseline and were exaggerated after exercise as evidenced by greater numbers of differentially genes in these molecular functions. CONCLUSIONS: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS.
Paradoxical Proliferation of Professorial Psychiatry? by Margaret Williams, 24th October 2004
White’s assertion that "Research about its cause has been hampered by the absence of a biological marker" causes a sharp intake of breath, as the medical, scientific and lay communities all know that whilst several biomarkers already exist, in the UK, the continued absence of a definitive biomarker is due to the absolute refusal of Government and government-funded bodies such as the MRC (who have been overly-influenced by psychiatrists of the "Wessely School") to fund any research that would reveal such biomarkers, yet sums of £11.1m are made available to these same psychiatrists who have vested interests in claiming "CFS/ME" as a psychosocial disorder.
It is noted that having had his vested interests publicly exposed (see "Notes on the involvement of Wessely et al with the Insurance Industry and how they deal with ME/CFS claims", particularly Appendix I that addresses the role of Peter Denton White as Chief Medical Officer for Swiss Re, which can be found at http://www.meactionuk.org.uk/Notes_on_the_Insurance_issue_in_ME.htm), White does now declare his own competing interests as being "consultancy work with the Department for Work and Pensions -- formerly the Department of Social Security -- and with the re-insurance company Swiss Re". People may draw their own conclusions about such competing interests.
Transparency in Government? by Eileen Marshall and Margaret Williams, 17th October 2004
Given the much-publicised emphasis on the need for "transparency" within all Government departments, one again has to ask how it can be acceptable for a "policy-maker" at the head of a Government Department clearly to have had such close involvement with an insurance company like UNUM whilst he was advising Government and formulating policy, given that (1) UNUM has been so publicly discredited for malpractice over legitimate claims made by those with ME/CFS (as well as other incapacitating disorders), and (2) the Court-documented aims of UNUM diametrically conflict with the needs of the sick and disabled whom the same Government department is charged with supporting.
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