My Interview with Dr. Simpson
- updated winter 2005
My Email Interview with Dr. Les Simpson
aletta:
On one of my reading jags on the internet, trying to answer the usual,
"how do I stay alive in the face of this" question, came across an article
on Mycoplasma (organism suspected in Gulf War Syndrome among other things).
I had questions, as it happened it mentioned a researcher in New Zealand
who could test for this blood anomaly. I sent email to both the author
(never answered) and Dr. Simpson.
Dr. Simpson was agreeable to spending time to answer my questions and
others the rest of you had. He continues to be there to answer questions
and do any tests that might be helpful.
Dr. Les Simpson, Ph.D. (pathology), now aged 79, has spent a lifetime
in medical research, except for a little time out for sheep farming he
lives in New Zealand. His Ph.D. is in Experimental Pathology. He has published
about 70 papers, mainly on auto immune disease, kidney function and disease.
I was born in the Netherlands, my father was a research chemist with
Shell Oil and Later the State Mines. In 1964 we emigrated to Canada
and my father took a position at Queen's University running the spectroscopy
laboratory at Queen's University Geological Department. My father
also ran tests as an independent for a variety of government (Canadian
and US programs including US Geological and NASA). I often assisted
my father in the lab preparing/running samples. I taught deaf children
to dance in Bellevile Ontario, lived in and around Kingston until 1974.
I had seizures in my teens, Bell's Palsy and diagnosed as epileptic.
My father died in 1974 from a brain tumour (as near I can tell, that information
is second hand) he had been a fanatic about his health, just to drop dead
at 46.
The current working diagnosis for me is Shy-Drager, my earliest symptoms
started in the mid eighties when I twice tested positively for AIDS (and
the Red Cross would no longer let me donate), in 1987 with a newer test
these were then considered false positives, by then I had hypoglycemia,
thyroid irregularities. I've had several calcified nodes removed
from the base of my skull (1987, 1992), a hear attack in 1992, passed out
often, polycythemia (of and on), tingling numbness, I've now been housebound
and unable to work for four years, I am 48. My daughter has trigeminal
neuralgia, my son has both psychiatric and neurological problems, both
are taking anti-seizure meds. I have half jokingly said I have the
slow release version of mad-cow, I believe in intuition. If this
can be either proved or disproved, I need to have that done, for myself
and especially my children.
Someone on the support group I run for people with a variety of rare
neurological problems asked what I thought caused this SDS, I said prions,
another member immediately sent me this article. Now I need to deal
with it.
Dr. Simpson:
You should understand that red cells are not living cells - they lose
the nucleus when the leave the bone marrow. For that reason they
respond to change in their environment by changing shape. In 1969
it was shown that red cells reversibly changed shape when the ionic nature
of their environment was changed. So this is not an inherited
feature - although there may be genetic factors involved.
Children with Down Syndrome in NZ$, Australia, South Africa and India had
changed red cell shape populations. Australians and an Indian baby
who took oil of evening primrose responded with greatly increased muscular
function. This in turn was associated with a reduction in body weight.
All sorts of things (both physiological and pathological) which change
the red cell environment induce red cell shape changes. In the premenstrual
week; after emotional upsets, after physical activity and during anaesthesia
red cells change shape. In any situation where the immune system
is stimulated - infections, graft rejection, the presence of tumors - changes
the shape populations and thus adversely affects the delivery of oxygen
and nutrients to the tissues. While I have been much more persistent
in this field than other authors - since the first observations in 1967,
many other authors have reported similar findings. So my work is
not entirely new.
My first thoughts on reading your brief medical history is the number
of diagnoses you have had for conditions which do not have a known cause.
Let me float an idea. Is it possible that your multi-system problems
is the outcome of altered blood rheology which is manifested as impaired
blood flow in the capillaries ? Normal tissue function
is ABSOLUTELY dependent upon normal rates of capillary blood flow because
this is the only way in which tissues are supplied with oxygen and nutrient
substrates.
Are you aware that depressive illnesses have been shown to have reduced
blood flow in the frontal regions of the brain ? In manic depression
I have found high values for flat cells - which explains why they benefit
from the fatty acids in fish oil - as they increase red cell flexibility.
I have had a brief look at your website and am intrigued by the range
of disorders you are addressing. BUT I cannot help but wonder if dysautonomias
in general are a reflection of the adverse effects on nerve function of
an inadequate rate of blood flow in the capillaries within the autonomic
nerves. In 1988 I published a long paper with 159 refs in which
I considered peripheral neuropathies in terms of the adverse effects of
altered blood rheology on intra-neural capillary blood flow. While
the main thrust considered diabetic neuropathy, I cannot see why the same
argument would not prevail in the sympathetic nervous system.
However, my experience is that neurologists seem not to recognize that
blood rheology has any patho-physiological significance.
aletta:
Just so I am clear please define what you mean by rheology??
I have suspected for some time (questions always met with raised eyebrow)
that my blood volume goes up and down (that to me would explain the occasional
bout of polycythemia and the edema and erratic heart rate)
Dr. Simpson:
Blood rheology relates to those factors which influence the flow properties
of blood. Red cell number is the main determinant of whole blood
viscosity - which would be high with polycythemia. Plasma and
serum viscosity are influenced by change in their chemistry.
Red cell deformability (or lack of it) is the major determinant (after
capillary diameter) of rate of flow in capillaries.
Edema is a consequence
of raised intra-capillary pressure - which occurs with poorly deformable
red cells.
If you have changed red cell shape populations then you have another
potentially pathogenic factor to consider. If you do not - then unless
there are accompanying vascular changes - blood flow is not contributing
to your problems. In disorders in which patients are told it
is all in their heads, patients tell me that to see altered red cells provides
them with an understanding that it is NOT all in their heads.
In conditions with chronic tiredness - who normally have normal lab
tests - they have altered red cells and the usual expressions of dysfunctionality
such as easy exhaustability and memory problems.
A problem (which I addressed in New Jersey Med in 1992) is why some
people get well in 10 days after a viral infection, while others become
chronically unwell. What I suggested is that the variability
of presenting symptoms probably reflected regions which by chance had a
preponderance of small capillaries. ( In accordance with the Poiseuille
formula flow through narrow tubes is related directly to the 4th power
of the tube radius. This means that even small variations in capillary
size will have quite marked effects on flow potential. Such variations
can be very localized. When I studied pre-menstrual syndrome
I was intrigued by one woman whose breast pain was confined to the left
breast.)
aletta:
Almost all of us have had to deal with the knee jerk reaction of nearly
every physician is to blame it on 'it's in her head' syndrome (even when
the heart attack was proved through testing). It took years to be
taken seriously enough to have orthostatic hypotension tested and proved.
since it is a blood pressure problem it should be obvious that blood flow
plays
a part, do You have any thoughts on the matter?
Dr. Simpson:
Together, blood is a thixotropic system which means that its viscosity
is flow-dependent. In the main vessels where flow rate is high, viscosity
is minimal, but in regions where flow rate is slow, viscosity is commensurately
increased. I have an idea that thixotropic phenomena play a
role in orthostatic states.
A major problem (from my point of view) is that orthostatic intolerance
is simply something that is demonstrated. During one visit to the
USA I raised the matter of midodrine for treatment - but this was
unknown.
aletta
I know several of us have been separately diagnosed with Raynauds,
some with thrombocythemia as well, all related to blood flow, do your have
any thoughts on that?
Dr.Simpson:
You could suggest to those with Raynauds that they could benefit from
taking 2 x 1000 mg capsules of salmon oil with food 3 times daily.
As Raynauds is associated with altered blood rheology it is not surprising
that there are multi-organ problems. The bleeding of thrombocythemia
makes me wonder if the platelet change is accompanied by a change in red
cell shape and blood rheology. As far as I can determine it
is another of those without knowledge of causation.
aletta
During the period of time I was also diagnosed as having "mild polycythemia",
can you relate polycythemia to rheology?
Dr.Simpson:
We have studied the urine of a polycythemic patient as part of a general
study of the effects of blood viscosity on kidney function.
Before, and after his polycythemia was corrected by serial bleeding
we obtained urine samples and assessed the size of the proteins in the
urine. As the polycythemic state was reduced so too was there a reduction
in the total amount of protein and the size of the protein molecules in
the urine. With a normal haematocrit there was normal urine and kidney
function.
An excessive intake of water in a situation where there was stiff red
cells would have two predictable effects. The higher than usual intracapillary
pressure would lead to edema. Because there would be a rise
in intraglomerular capillary pressure, kidney filtration would be increased.
Because of the effects of filtration, blood leaving the glomerulus would
be more viscous and this would have an adverse effect on tubular re-absorption
- so urine volume would increase.
aletta
Purpura and odd bleeding has been experienced by some of us, is there
an explanation for this?
Dr.Simpson:
In conditions with altered red cell shape populations, it is common
for bruising to occur even after a light bump. This indicates
the higher than normal intra-capillary pressure which accompanies the presence
of shape-changed, poorly deformable red cells.
The discoloration which indicates a "bruise" is simply an indication
that during the knock or bump which caused the bruise, red cells have been
forced out of their blood vessels. Eventually the cells are
removed by phagocytic white cells - and the discoloration is gone.
If easy bruising is a common factor then I would expect the presence
of abnormal red cell shape populations.
On diet:
I presume that you are aware of the potential dangers in special diets.
There have been a number of reports recently which have drawn attention
to the fact that vegetarians have a shorter lifespan than omnivores.
On Physicians:
I have done a great deal of lecturing (Bellevile, Brockville and others)
and during these I urge patients not to be too hard on doctors - they are
following their training. The problem is higher up - those
who determine the content of medical school curricula are the real problem.
Tests your doctor can do:
whole blood viscosity;
plasma viscosity;
serum viscosity and
red cell deformability.
aletta:
I have been unable to sleep unaided with medication for four years,
is it possible that a disruption or inadequate blood-flow could cause this
to happen?
Dr.Simpson:
A 1967 textbook on neurobiology reported that sleep problems can arise
in situations where the hypothalamus has an insufficient rate of blood
flow.
aletta
Is there a test to assess capillary dimensions?
Dr.Simpson:
Assessment of capillary dimensions is not a simple matter - and probably
would be best done post-mortem. BUT it is possible that conjunctival capillaries
would provide a good sample. When I set out to explore this through
the eye department, the cost of doing the necessary photography put the
study beyond my reach.
An ophthalmologist would be knowledgeable about conjunctival photography.
If you get your conjunctivas photographed please ask for a scale to be
included so that vessel diameter can be measured. (Please request
a copy to bee sent to Dr. Simpson) As I understand it - the eye would be
"blown up" allowing a larger area of the conjunctiva to be photographed.
Even though the ME and FM papers relate to different disorders
I think that you should be able to discern the message - that tissue function
cannot be normal if oxygen is not available.
I was invited to speak in Berkeley, California by a well known psychologist
-Sheila Bastien. At the end of question time I asked her "
Do you think that normal psychology can occur when there is sub-normal
blood flow in the brain ?" Her reply "No chance."
other q&a
This from Belinda, she's been diagnosed with CGBD and lives in Atlanta,
Georgia, 41 years old, one last wobble away from a wheelchair, the pains
she describes, I also experience, no doubt more of us as well:
When you speak with Dr Simpson again will you ask him if he knows why
I have different places on my head at different times that feels a little
swollen but also bruised. It hurts horribly for a few days and then it
is gone. A few days later I will get another place on my head that feels
the same way. I wonder if that has anything to do with my blood running
through my head. I also have times when it feels like someone is
taking a knife and stabbing me with it. It just is in one area on my head.
After a while it stops. Strange, I know.
Dr.Simpson:
Belinda's problems certainly COULD be related to altered blood
rheology manifesting as easy bruising because of stiff red cells.
The focal stabbing pains might also be blood flow related but need
to be explored by PET scanning to see if a cause can be determined.
the next round:
aletta:
Does it make a difference which kind of fish oil you use? Still
gag at the thought of it, was given so much cod liver oil with a lump of
sugar nightly as a child, at least it is in pills now. The pharmacy
here has cod, salmon or halibut.
Dr.Simpson:
I have never had the option of having 3 species of oil - in this part
of the world I suspect that a number of different species are involved.
Without any other reason - if prices are not different I would go for the
salmon oil - but that is a personal preference. Note that you
are not using LIVER oil. The omega-3s come from the flesh of the
fish.
aletta:
What does it do? plump up flat cells or just make them more slippery?
The oil has the effect of increasing the fluidity of the lipid bilayer
of the red cell membrane - possibly through the action of PGE3. PGE1
which is increased by evening primrose oil has the same effect.
As the action takes place within the red cell membrane I have the impression
that the cells become more deformable without necessarily changing shape.
aletta:
In plain language deformable = pliable/flexible, less likely to plug
things up?
Dr.Simpson:
The key point is that red cells are larger than most capillaries, which
means that they must change shape , i.e. to deform , in order to traverse
the capillary bed. So poorly deformable red cells may cause a variety of
problems by their ability to "plug things up" or more commonly to slow
down the rate of passage through the capillaries. This means that the rate
of delivery of oxygen and nutrients will be reduced and that wastes such
as carbon dioxide are not removed.
This means that "flexibility and pliability" are not QUITE the same.
Would you believe that one of the papers which I quote concerning red
cell shape changes is a Japanese report of the red cells in spinocebellar
degeneration - which could well be spinocerebellar ataxia !!
In early idiopathic Parkinsonism there is Loss of energy, easy fatigability,
muscle pains, joint pains, cramps - all of these are symptoms of ME, CFIDS,
CFS - where there are shape-changed red cells - mainly flat cells. In a
report I sent recently to Gerontology of the red cells in people 60 years
of age and older - high values for flat cells were found.
There is much evidence of hypometabolism ( which I interpret as a consequence
of inadequate blood flow) by PET scans and the few comments re SPECT scans
showed reduced blood flow in the frontal regions of the brain - as has
been reported in 3 studies relating to depression.
All this leaves me with the very strong impression that altered blood
rheology manifested as altered red cell shape populations are a significant
feature of these neurodegenerative disorders.
aletta:
The lack of funding in your research and a general disinterest in RBC
related illness is due to what - in your opinion??
Dr.Simpson:
You asked "Is that due to a general disinterest in RBC related illness
?" I think the primary problem is that blood rheology is not taught at
medical schools - therefore to the medical profession it does not exist.
So there is a significant component of the medical literature which is
unknown to, and therefore unused by the medical profession.
Diabetes is a good example. There is a very large literature which describes
the abnormal blood rheology of the diabetic state - which is totally ignored
by physicians. Although the first scanning electron microscopy of red cells
was published in 1967 and showed different shapes of red cells, the current
teaching is that all red cells are biconcave discocytes. In 1989 I published
in the Br Journal of Haematology a report showing that the red cells of
man and animals can be classified into 6 different shape classes that paper
has never been quoted in a medical journal.
What this implies is that the progressive nature of neurodegenerative
disorders will continue while abnormal blood rheology exists. This raises
the question about the POTENTIAL benefits of improving blood rheology to
slow down a progressive process. A long-term French study (4 years) used
a drug (pentoxifylline) which reduces blood viscosity and increases red
cell deformability in diabetics. At the end of the 4 years none of the
complications of the diabetic state had developed. Would early OPCA respond
similarly ?????
aletta:
It also means to me that we are lumped together and swept nicely under
the rug, the numbers small enough not to need bother. Once Pakinsonian
symptoms appear there are avenues available but not before.
No, the classification does not lump you all together - Shy-Drager
was discussed separately. I think that the replacement of OPCA by MSA-C
was based upon similarity of histological findings.
I agree that when the symptoms of Parkinson's appear it MAY be too late
- BUT it is also possible that by reversing the altered blood rheology,
the rate of progression can be very greatly reduced.
It seems to me that the progressive destruction of neurones could be
the consequence of an inadequate rate of blood flow leading on to cessation
of blood flow with resulting cell death. And neurones cannot be replaced.
aletta
What are the likely triggers for these RBCs gone bad? Could it
be the disease process itself that is to blame (altered programming, faulty
DNA), and exhausted, depleted body trying to cope?
Dr.Simpson:
All sorts of events may alter the red cell environment sufficiently
to stimulate red cell shape change. Infections through to toxins could
have such effects. Maybe the problem could be a faulty biochemical pathway.
You should understand that the changes are not fixed and immutable - red
cell shape is dynamic, so at least in theory -given the correct agent -
it would be able to restore red cell shape to normal.
aletta:
What has been the obstacle?? Is it uniformly so or are there
countries (France perhaps) who are adding it in to the curriculum??
Dr.Simpson:
For the life of me I cannot understand why blood rheology should be
ignored. Blood flow is necessary for life - but n o information provided
by haematology labs is relevant to blood flow. If you are aware of the
writings of Thomas Kuhn, then you would know that what we are seeing is
the strength of support enjoyed by the existing paradigm. To retain their
place in the sun supporters of the current concept of red cell shape simply
ignore anything to the contrary. They KNOW they are correct !!!!! In most
countries there are small pockets of blood rheologists but their critical
mass is not sufficient to push for recognition and a change.
aletta:
Is there a geographic pattern for these different cell shapes??
The Netherlands is notoriously high in Neurodegenerative disorders?
To the best of my knowledge there is no geographic pattern I have had
samples from Australia, Britain, Canada, Denmark, France, Holland, Ireland,
Poland, South Africa and the USA, and they all showed the same cell shapes
albeit in different proportions depending upon their diagnosis.
aletta:
Is pentoxifylline past
testing and on the market, anywhere??
Dr.Simpson:
Yes, pentoxifylline is marketed as TRENTAL and has been around for
many years.
aletta:
I did check my reference book "the Canadian Medical Association Guide
to Prescription and Over the Counter Drugs) - not a terribly up to
date - 1995, which does indeed list Trental or Pentoxifylline, mentions
making red blood cells more flexible, part of the drug group vasodilators,
wondering why no doctors had thought this worth mentioning since my DX
of peripheral vascular disease has been in my file for about 6 years
aletta:
Perhaps we can get a study done here? If we scream loud enough.
Dr.Simpson
You are absolutely correct with regard to tests. Convincing any authority
is a numbers game - and until there is a substantial body of data relating
to the blood of ataxic people it is unlikely anything will happen.
aletta;
Is it possible that untreated CFS, ME etc. progresses to neurodegenerative
illness? Much like an untreated cold can turn to pneumonia?
Most if not all of our group are very driven work-oriented individuals
(the type to put off seeing a doctor) who were diagnosed after many years
of being belittled and trivialized, could that plus a predisposition to
neurological illness be the cause??
Dr.Simpson:
With regard to your query re the disease process - it is possible that
diabetes may provide some information.
In that disorder there is evidence of blockage and subsequent re-canalisation
of capillaries. This type of change is manifested as "onion-skin" type
changes in the walls of capillaries. The "onion-skins" are successive wall
layers (basement membranes) which simply accumulate because they are not
degradeable. My concepts concerning basement membranes challenged existing
concepts - and although others have published observations supporting my
concept I think it remains buried because of an important proffessor at
Harvard. In other words the messenger is of greater significance than the
message.
My interpretation of this type of disorder (based upon my findings from
the aging study) is that a lack of treatment of an inadequate blood flow
will be a continuing loss of more peripheral tissue in the brain - or in
those parts of the brain which by chance have small capillaries. So there
will be a progressive deterioration of function..
part 2-3 continued
30/01/03
aletta:
While poking around the Internet, I also found this article and the
one below it on Shy-Drager (cured by a name change). Perhaps it would
not be too great a jump for him to consider that hypo perfusion due to
RBC anomalies might be at the root of neuronal loss in SDS and the like.
The last completed task on my part was the /dizzydancers.shtml
where I'm collecting some of a growing theory why dancers can deal with
this better, live longer, or become stricken with this paticularly.
*******************
articles referred to:
Mean Red Cell Volume as a Correlate of Blood Pressure
Dan S. Sharp, MD, PhD; J. David Curb, MD, MPH; Irwin J. Schatz, MD;
Herbert J. Meiselman, ScD; Timothy C. Fisher, MD; Cecil M. Burchfiel, PhD;
Beatriz L. Rodriguez, MD, PhD; Katsuhiko Yano, MD
From the Honolulu Epidemiology Research Unit (D.S.S., C.M.B.), Field
Studies and Clinical Epidemiology Scientific Research Group, Epidemiology
and Biometry Program, Division of Epidemiology and Clinical Applications,
National Heart, Lung, and Blood Institute, Honolulu, Hawaii; Honolulu Heart
Program (J.D.C., B.L.R., K.Y.), Kuakini Medical Center, Honolulu, Hawaii;
Department of Medicine (J.D.C., I.J.S., B.L.R.), John A. Burns School of
Medicine, University of Hawaii at Manoa (Honolulu); and Department of Physiology
and Biophysics (H.J.M., T.C.F.), University of Southern California School
of Medicine (Los Angeles).
Correspondence to Dr Dan S. Sharp, Honolulu Heart Program, National
Heart, Lung, and Blood Institute, 347 N Kuakini St, Honolulu, HI 96817.
E-mail dan@hhs.cba.hawaii.edu.
Background Clinical studies suggest that hypertensives have lower mean
corpuscular volume (MCVs) than do normotensives. Epidemiological studies
show no relation or higher MCVs. In the present study of elderly men (71
to 93 years of age) of the Honolulu Heart Program, elements of both findings
are confirmed.
Methods and Results Three groups are identified: (1) those receiving
no hypertension treatment, (2) those receiving treatment with any diuretic,
and (3) those receiving treatment with nondiuretics only. MCV is lower
in group 3 than in group 1 (-0.85 fL, P<.001) but the same in groups
1 and 2. Within groups 1 and 3, inverse relations of -0.22 and -0.09 mm
Hg/fL (P<.05) are noted for systolic (SBP) and diastolic (DBP) blood
pressures. No relations are observed in group 2. MCV and red blood cell
count (RBC) are inversely correlated (r=-.45). In group 2, adjustment for
RBC unmasks a direct relation between MCV and SBP (0.5 mm Hg/fL, P=.02)
and DBP (0.3 mm Hg/fL, P=.02). In groups 1 and 3, relations between SBP
and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding
RBC plus an MCVxRBC interaction is significant (P<.001). DBP is 5 mm
Hg greater in the highest RBC quartile than in the lowest. A +3 mm Hg difference
between extreme MCV quartiles is noted only at high RBC levels.
Conclusions The relation between blood pressure and red cell measures
is probably mediated by whole blood viscosity. Hematocrit is a determinant
of whole blood viscosity. Viscosity affects peripheral resistance to blood
flow, and peripheral resistance affects DBP. At high RBC levels, MCV may
be "downregulated." This may lower whole blood viscosity and partially
reduce DBP without compromising flow.
Key Words: blood pressure • blood viscosity • erythrocytes • vascular
resistance
Copyright © 1996 by the American Heart Association.
Dr. Irwin Schatz, Chair Queen's University Tower, 7th Floor 1356 Lusitana
St. Honolulu, HI 96813 Ph: (808) 586-2910 Fax: (808) 586-7486 [an error occurred while processing this directive]
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