CFS-FMSsupport] University of Miami CFS Study
The CFIDS Chronicle, Fall 2002
www.cfids.org/archives/20...ll-toc.asp
Chronicle Q&A:
Procrit Trial Focuses on Red Blood Cells
By Mark Giuliucci
Researchers at the University of Miami are testing the effects of the
drug Procrit (epoetin alfa) on people with CFIDS. The drug, also
manufactured as Epogen, increases the body's production of
oxygen-carrying red blood cells. The study has received substantial coverage from
national media outlets this year. As part of an ongoing Question and
Answer series with CFIDS researchers, the Chronicle interviewed Barry
Hurwitz, PhD, the principal investigator in the Procrit-CFIDS study.
Q: What is the theory behind Procrit and CFIDS?
A: Procrit was developed to treat anemia. It's highly effective in
inducing bone marrow to produce red blood cells. Procrit has been
used on two groups of patients so far: people who have cancer and have
undergone chemotherapy, and people with kidney disease who are on
dialysis. To date the medication has not been used on CFIDS patients in a
large clinical trial.
Our preliminary data indicated that many of our CFIDS patients who
had difficulty with fainting spells and light-headedness also displayed
decreased red blood cell volume. We hypothesized that the lack of
sufficient oxygen supply could be a cause for these symptoms and
possibly explain the fatigue as well. The study we're conducting is looking
at whether increasing red blood cell volume can improve these
symptoms in people diagnosed with CFIDS.
Q: Do people with CFIDS have low numbers of red blood cells?
A: We have found that 60-70 percent of people with CFIDS have
low-normal, or below-normal, red blood cell volume. This was not known
before we began our work. It's usually missed by standard blood tests.
The test we use is called a dual tag blood volume test. It is the
gold standard, the most accurate way to measure both plasma volume and
red blood cell volume in the blood. It's commonly done in the
radiology departments at most hospitals.
It's important for those who are wondering if they have red blood
cell volume deficit that the right test be performed. Some tests only
measure the plasma volume and estimate the red blood cell volume. Those
are inaccurate. For instance, there's a measure called hematocrit.
The percentage of red blood cells in the blood is derived from a drop
of blood, but it's really an estimate.
Q: How is the Procrit study being run?
A: We have a randomized, placebo-controlled trial funded by the
National Institutes of Health's National Heart, Lung and Blood
Institute. Dr. Nancy Klimas and I are the principal investigators, and we work
with a team of other medical scientists. It's a four-year study, and
we're in year two. We want to enroll 150 people, and we're about
halfway to that goal.
We assess individuals as to whether or not they have diminished red
blood cell volume. We also give them a complete cardiovascular workup,
and take other measures that will help us test what role the immune
system might play in influencing red blood cell volume.
The actual treatment phase lasts four months, with check-ups every
two weeks. People with low red blood cell volume are randomized to
Procrit or placebo treatment. People with low red blood cell volume who
receive placebo will later receive an opportunity to obtain the four
months of Procrit treatment and repeat the testing.
If it's determined up front that you do not have low red blood cell
volume, you're given a placebo. That way we can compare people who
have low red blood cell volume to those with normal blood volume levels.
The drug is administered three times a week by injection. Subjects
are tested before treatment begins and after the four months of
treatment. By using daily diaries, simple reflex tests and a tilt test we
examine changes in CFIDS symptomatology, as well as the individual's
ability to control the circulatory system. These circulatory tests are
performed because in CFIDS patients the light-headedness and fainting
typically occur when the person is in an upright posture, suggesting
a circulatory regulation problem.
Q: Is it too early to comment on study results?
A: Yes, because it's a double-blind study. The experimenters and
the subjects are unaware of the treatment assignments until after the
study is finished. Then we'll be able to analyze the results. Subjects
are provided copies of their test results at the completion of their
testing.
Q: What is the best-case scenario?
A: If individuals are fatigued, one possible cause is a lack of
oxygenation in the blood, or an inability to transport oxygen. If you
have diminished red blood cell volume, then you have less capability to
deliver oxygen to the cells. There's a high probability that if we're
able to increase red blood cell volume it will diminish fatigue,
assuming that fatigue is a function of the capacity to deliver oxygen to
the tissues.
Q: If it turns out that Procrit does help, how long would
treatments have to be taken for a lasting effect?
A: That's an empirical question. First, we'll have to determine if
there is a measurable change in people who take the drug - in fatigue
levels, quality of life, exercise fitness, ability to sustain an
upright posture, and in immune function and profile.
If there is a change, then the next question is whether the treatment
has to be maintained for a long period of time. One possibility is
that restoring red blood cell volume will have a positive effect on
what's causing the problem in the first place. Theoretically, the
treatments could end at that point. That would be a very positive outcome,
because at this time Procrit is an expensive drug.
Alternatively, we'll have to keep searching for the main cause for
the decreased red blood cell volume. We suspect that the immune system
may be involved. That's why we're taking a number of immune system
measures, to find out how the immune system might be related to the
decrease in red blood cell production.
Q: Why is there such a buzz about this study?
A: The fact is that there's no accepted treatment for CFIDS. People
are desperate to find some recognizable cause. There's obviously a
strong demand for an effective treatment.
It is very exciting to have learned from our study so far that 60-70
percent of people with CFIDS have diminished red blood cell volume.
We did not know that before we began the study. To me, that tells
people that there's something really physically wrong with them. For
individuals who have been told before that it's all in your head, that
you're malingering, the knowledge that there are real physical changes
going on is confirming for them.
Even if Procrit does not improve CFIDS symptoms, the information
we're collecting regarding circulatory functioning and immune system
interactions in relation to fatigue will shed a great deal of light on
some of the important disease pathophysiology.
Q. How can people participate in the study?
A: We're including individuals18-55 years of age who have been
diagnosed with CFIDS by their physicians. Participants must have no
diagnosed medical history of abnormal cardiovascular conditions, epilepsy,
chronic respiratory conditions, alcohol or drug abuse, and must not
be taking prescribed medications that would have an impact on their
cardiovascular system. Participants must be willing to be available for
assessments at the study site every two weeks for a seven-month
period. They have to travel to Miami at their own expense. Qualifying
people must fill out and submit a questionnaire on our Web site,
www.bmrc.miami.edu/resear...ocrit.asp. Other questions
or comments may be forwarded via e-mail to CFSresearch@miami.edu.
By Jule Klotter
(Townsend Letter, issue: November 2001)
According to an article by Maryann Spurgin, Ph.D., New Zealand researcher Dr. L.O. Simpson has theorized that myalgic encephalomyelitis (ME), also known as Chronic Fatigue Immune Deficiency Syndrome (CFIDS), results from "insufficient oxygen availability due to impaired capillary blood flow."
Simpson attributes the impaired capillary blood flow to smaller-than-usual capillaries and to the presence of abnormal red blood cells (nondiscocytes).
In healthy people, most red blood cells are smooth-surfaced and concave-shaped with a donut-like appearance. These discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid.
Abnormal red blood cells lack flexibility that allow them to enter tiny capillaries. These nondiscocytes are characterized by a variety of irregularities, including surface bumps or ridges, a cup or basin shape, and altered margins instead of the round shape found in discocytes.
When people become ill or physically stressed, a higher percentage of discocytes transform into the less flexible nondiscocytes. Simpson says that the blood samples of marathon runners show a higher percentage of cup-shaped nondiscocytes (somatocytes) after a race. This higher percentage soon reverts to pre-race, normally-low levels of abnormally-shaped cells. Similarly, researchers found that the percentage of nondiscocytes in people with a viral head cold peaked on the fifth day and declined by the tenth day.
Simpson found that people with ME/CFIDS have higher percentages of nondiscocytes than people with other chronic illnesses, such as Lupus, multiple sclerosis, Huntington's disease, malaria, and diabetes. In addition, the percentages of cup-shaped somatocytes in ME/CFIDS patients can remain high for months, inhibiting blood flow.
Simpson believes that, in ME/CFIDS, either the mechanism whereby red blood cells revert to the discocyte form is hampered for some reason or that whatever triggered the red blood cells to transform into nondiscocytes remains in effect, albeit unidentified. Ms. Spurgin notes that red blood cell morphology is also affected by toxic chemicals, providing a possible link between ME/CFIDS, environmental illness and multiple chemical sensitivity, and Gulf War Syndrome.
Simpson found that vitamin B12 injections reduced nondiscocyte levels in some ME patients. These patients also experienced symptomatic improvement. Patients whose nondiscocyte levels remain unaffected by the B12 injections noticed no improvement. Research with diabetic patients found that omega-3 fatty acids can also reduce nondiscocyte levels and improve capillary flow; and omega-6, in the form of evening primrose oil, has improved blood filterability in cigarette smokers.
"The Role of Red Blood Cell Morphology in the Pathogenesis of ME/CFIDS" by Maryann Spurgin, Ph.D., The CFIDS Chronicle, Summer 1995 discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary, beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid. Abnormal red blood cells lack flexibility that allow them to enter tiny capillaries. These nondiscocytes are characterized by a variety of irregularities, including surface bumps or ridges, a cup or basin shape, and altered margins instead of the round shape found in discocytes.
When people become ill or physically stressed, a higher percentage of discocytes transform into the less flexible nondiscocytes. Simpson says that the blood samples of marathon runners show a higher percentage of cup-shaped nondiscocytes (somatocytes) after a race. This higher percentage soon reverts to pre-race, normally-low levels 'of abnormally-shaped cells. Similarly, researchers found that the percentage of nondiscocytes in people with a viral head cold' peaked on the fifth day and declined by the tenth day.
Simpson found that people with ME/CFIDS have higher percentages of nondiscocytes than people' with other chronic illnesses, such as Lupus, multiple sclerosis, Huntington's disease, malaria, and diabetes. In addition, the percentages of cup-shaped somatocytes in ME/CFIDS patients can remain high for months, inhibiting blood flow.
Simpson believes that, in ME/CFIDS, either the mechanism whereby red blood cells revert to the discocyte form is hampered for some reason or that whatever triggered the red blood cells to transform into nondiscocytes remains in effect, albeit unidentified. Ms. Spurgin notes that red blood cell morphology is also affected by toxic chemicals, providing a possible link between ME/CFIDS, environmental illness and multiple chemical sensitivity, and Gulf War Syndrome.
Simpson found that vitamin B12 injections reduced nondiscocyte levels in some ME patients. These patients also experienced symptomatic improvement. Patients whose nondiscocyte levels remain unaffected by' the B12 injections noticed no improvement. Research with diabetic patients found that omega-3 fatty acids can also reduce nondiscocyte levels and improve capillary flow; and omega-6, in the form of evening primrose oil, has improved blood filterability in cigarette smokers.
Reference: "The Role of Red Blood Cell Morphology in the Pathogenesis of ME/CFIDS" by Maryann Spurgin, PhD, The CFIDS Chronicle, Summer 1995
COPYRIGHT 2001 The Townsend Letter Group; COPYRIGHT 2001 Gale Group.
The CFIDS Chronicle, Fall 2002
www.cfids.org/archives/20...ll-toc.asp
Chronicle Q&A:
Procrit Trial Focuses on Red Blood Cells
By Mark Giuliucci
Researchers at the University of Miami are testing the effects of the
drug Procrit (epoetin alfa) on people with CFIDS. The drug, also
manufactured as Epogen, increases the body's production of
oxygen-carrying red blood cells. The study has received substantial coverage from
national media outlets this year. As part of an ongoing Question and
Answer series with CFIDS researchers, the Chronicle interviewed Barry
Hurwitz, PhD, the principal investigator in the Procrit-CFIDS study.
Q: What is the theory behind Procrit and CFIDS?
A: Procrit was developed to treat anemia. It's highly effective in
inducing bone marrow to produce red blood cells. Procrit has been
used on two groups of patients so far: people who have cancer and have
undergone chemotherapy, and people with kidney disease who are on
dialysis. To date the medication has not been used on CFIDS patients in a
large clinical trial.
Our preliminary data indicated that many of our CFIDS patients who
had difficulty with fainting spells and light-headedness also displayed
decreased red blood cell volume. We hypothesized that the lack of
sufficient oxygen supply could be a cause for these symptoms and
possibly explain the fatigue as well. The study we're conducting is looking
at whether increasing red blood cell volume can improve these
symptoms in people diagnosed with CFIDS.
Q: Do people with CFIDS have low numbers of red blood cells?
A: We have found that 60-70 percent of people with CFIDS have
low-normal, or below-normal, red blood cell volume. This was not known
before we began our work. It's usually missed by standard blood tests.
The test we use is called a dual tag blood volume test. It is the
gold standard, the most accurate way to measure both plasma volume and
red blood cell volume in the blood. It's commonly done in the
radiology departments at most hospitals.
It's important for those who are wondering if they have red blood
cell volume deficit that the right test be performed. Some tests only
measure the plasma volume and estimate the red blood cell volume. Those
are inaccurate. For instance, there's a measure called hematocrit.
The percentage of red blood cells in the blood is derived from a drop
of blood, but it's really an estimate.
Q: How is the Procrit study being run?
A: We have a randomized, placebo-controlled trial funded by the
National Institutes of Health's National Heart, Lung and Blood
Institute. Dr. Nancy Klimas and I are the principal investigators, and we work
with a team of other medical scientists. It's a four-year study, and
we're in year two. We want to enroll 150 people, and we're about
halfway to that goal.
We assess individuals as to whether or not they have diminished red
blood cell volume. We also give them a complete cardiovascular workup,
and take other measures that will help us test what role the immune
system might play in influencing red blood cell volume.
The actual treatment phase lasts four months, with check-ups every
two weeks. People with low red blood cell volume are randomized to
Procrit or placebo treatment. People with low red blood cell volume who
receive placebo will later receive an opportunity to obtain the four
months of Procrit treatment and repeat the testing.
If it's determined up front that you do not have low red blood cell
volume, you're given a placebo. That way we can compare people who
have low red blood cell volume to those with normal blood volume levels.
The drug is administered three times a week by injection. Subjects
are tested before treatment begins and after the four months of
treatment. By using daily diaries, simple reflex tests and a tilt test we
examine changes in CFIDS symptomatology, as well as the individual's
ability to control the circulatory system. These circulatory tests are
performed because in CFIDS patients the light-headedness and fainting
typically occur when the person is in an upright posture, suggesting
a circulatory regulation problem.
Q: Is it too early to comment on study results?
A: Yes, because it's a double-blind study. The experimenters and
the subjects are unaware of the treatment assignments until after the
study is finished. Then we'll be able to analyze the results. Subjects
are provided copies of their test results at the completion of their
testing.
Q: What is the best-case scenario?
A: If individuals are fatigued, one possible cause is a lack of
oxygenation in the blood, or an inability to transport oxygen. If you
have diminished red blood cell volume, then you have less capability to
deliver oxygen to the cells. There's a high probability that if we're
able to increase red blood cell volume it will diminish fatigue,
assuming that fatigue is a function of the capacity to deliver oxygen to
the tissues.
Q: If it turns out that Procrit does help, how long would
treatments have to be taken for a lasting effect?
A: That's an empirical question. First, we'll have to determine if
there is a measurable change in people who take the drug - in fatigue
levels, quality of life, exercise fitness, ability to sustain an
upright posture, and in immune function and profile.
If there is a change, then the next question is whether the treatment
has to be maintained for a long period of time. One possibility is
that restoring red blood cell volume will have a positive effect on
what's causing the problem in the first place. Theoretically, the
treatments could end at that point. That would be a very positive outcome,
because at this time Procrit is an expensive drug.
Alternatively, we'll have to keep searching for the main cause for
the decreased red blood cell volume. We suspect that the immune system
may be involved. That's why we're taking a number of immune system
measures, to find out how the immune system might be related to the
decrease in red blood cell production.
Q: Why is there such a buzz about this study?
A: The fact is that there's no accepted treatment for CFIDS. People
are desperate to find some recognizable cause. There's obviously a
strong demand for an effective treatment.
It is very exciting to have learned from our study so far that 60-70
percent of people with CFIDS have diminished red blood cell volume.
We did not know that before we began the study. To me, that tells
people that there's something really physically wrong with them. For
individuals who have been told before that it's all in your head, that
you're malingering, the knowledge that there are real physical changes
going on is confirming for them.
Even if Procrit does not improve CFIDS symptoms, the information
we're collecting regarding circulatory functioning and immune system
interactions in relation to fatigue will shed a great deal of light on
some of the important disease pathophysiology.
Q. How can people participate in the study?
A: We're including individuals18-55 years of age who have been
diagnosed with CFIDS by their physicians. Participants must have no
diagnosed medical history of abnormal cardiovascular conditions, epilepsy,
chronic respiratory conditions, alcohol or drug abuse, and must not
be taking prescribed medications that would have an impact on their
cardiovascular system. Participants must be willing to be available for
assessments at the study site every two weeks for a seven-month
period. They have to travel to Miami at their own expense. Qualifying
people must fill out and submit a questionnaire on our Web site,
www.bmrc.miami.edu/resear...ocrit.asp. Other questions
or comments may be forwarded via e-mail to CFSresearch@miami.edu.
By Jule Klotter
(Townsend Letter, issue: November 2001)
According to an article by Maryann Spurgin, Ph.D., New Zealand researcher Dr. L.O. Simpson has theorized that myalgic encephalomyelitis (ME), also known as Chronic Fatigue Immune Deficiency Syndrome (CFIDS), results from "insufficient oxygen availability due to impaired capillary blood flow."
Simpson attributes the impaired capillary blood flow to smaller-than-usual capillaries and to the presence of abnormal red blood cells (nondiscocytes).
In healthy people, most red blood cells are smooth-surfaced and concave-shaped with a donut-like appearance. These discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid.
Abnormal red blood cells lack flexibility that allow them to enter tiny capillaries. These nondiscocytes are characterized by a variety of irregularities, including surface bumps or ridges, a cup or basin shape, and altered margins instead of the round shape found in discocytes.
When people become ill or physically stressed, a higher percentage of discocytes transform into the less flexible nondiscocytes. Simpson says that the blood samples of marathon runners show a higher percentage of cup-shaped nondiscocytes (somatocytes) after a race. This higher percentage soon reverts to pre-race, normally-low levels of abnormally-shaped cells. Similarly, researchers found that the percentage of nondiscocytes in people with a viral head cold peaked on the fifth day and declined by the tenth day.
Simpson found that people with ME/CFIDS have higher percentages of nondiscocytes than people with other chronic illnesses, such as Lupus, multiple sclerosis, Huntington's disease, malaria, and diabetes. In addition, the percentages of cup-shaped somatocytes in ME/CFIDS patients can remain high for months, inhibiting blood flow.
Simpson believes that, in ME/CFIDS, either the mechanism whereby red blood cells revert to the discocyte form is hampered for some reason or that whatever triggered the red blood cells to transform into nondiscocytes remains in effect, albeit unidentified. Ms. Spurgin notes that red blood cell morphology is also affected by toxic chemicals, providing a possible link between ME/CFIDS, environmental illness and multiple chemical sensitivity, and Gulf War Syndrome.
Simpson found that vitamin B12 injections reduced nondiscocyte levels in some ME patients. These patients also experienced symptomatic improvement. Patients whose nondiscocyte levels remain unaffected by the B12 injections noticed no improvement. Research with diabetic patients found that omega-3 fatty acids can also reduce nondiscocyte levels and improve capillary flow; and omega-6, in the form of evening primrose oil, has improved blood filterability in cigarette smokers.
"The Role of Red Blood Cell Morphology in the Pathogenesis of ME/CFIDS" by Maryann Spurgin, Ph.D., The CFIDS Chronicle, Summer 1995 discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary, beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid. Abnormal red blood cells lack flexibility that allow them to enter tiny capillaries. These nondiscocytes are characterized by a variety of irregularities, including surface bumps or ridges, a cup or basin shape, and altered margins instead of the round shape found in discocytes.
When people become ill or physically stressed, a higher percentage of discocytes transform into the less flexible nondiscocytes. Simpson says that the blood samples of marathon runners show a higher percentage of cup-shaped nondiscocytes (somatocytes) after a race. This higher percentage soon reverts to pre-race, normally-low levels 'of abnormally-shaped cells. Similarly, researchers found that the percentage of nondiscocytes in people with a viral head cold' peaked on the fifth day and declined by the tenth day.
Simpson found that people with ME/CFIDS have higher percentages of nondiscocytes than people' with other chronic illnesses, such as Lupus, multiple sclerosis, Huntington's disease, malaria, and diabetes. In addition, the percentages of cup-shaped somatocytes in ME/CFIDS patients can remain high for months, inhibiting blood flow.
Simpson believes that, in ME/CFIDS, either the mechanism whereby red blood cells revert to the discocyte form is hampered for some reason or that whatever triggered the red blood cells to transform into nondiscocytes remains in effect, albeit unidentified. Ms. Spurgin notes that red blood cell morphology is also affected by toxic chemicals, providing a possible link between ME/CFIDS, environmental illness and multiple chemical sensitivity, and Gulf War Syndrome.
Simpson found that vitamin B12 injections reduced nondiscocyte levels in some ME patients. These patients also experienced symptomatic improvement. Patients whose nondiscocyte levels remain unaffected by' the B12 injections noticed no improvement. Research with diabetic patients found that omega-3 fatty acids can also reduce nondiscocyte levels and improve capillary flow; and omega-6, in the form of evening primrose oil, has improved blood filterability in cigarette smokers.
Reference: "The Role of Red Blood Cell Morphology in the Pathogenesis of ME/CFIDS" by Maryann Spurgin, PhD, The CFIDS Chronicle, Summer 1995
COPYRIGHT 2001 The Townsend Letter Group; COPYRIGHT 2001 Gale Group.
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