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A CLASSICAL EXAMPLE OF MEDICAL
QUACKERY
21st CENTURY
STYLE:
THE NON
SPECIFICITY
OF "PROSTATE
SPECIFIC" ANTIGEN
By Daniel H Duffy
Sr, DC
Rewritten
September 6,
2004
On Saturday, June 15, 2002 a long time patient
came in for his regular checkup and treatment via AK. He is now 77 and has been
a patient for almost 30 years. He was preparing for a senior citizen race
walking event.
On a recent visit to His MD, he was examined in
orthodox fashion and found to have an elevated PSA for which an
incredibly expensive drug was prescribed. It cost over $1000 for 90 pills.
Three of the pills immediately made him sick so he stopped taking the drug
after his first three doses.
Of course, he only paid five of the $1000 plus dollars it
cost - we the taxpayers paid the rest - thanks to the socially disastrous
efforts of LBJ - the father of MEDICARE.* [see short story at the end of the Prostate
article].
HERE ARE THE FACTS ON PROSTATE SPECIFIC
ANTIGEN, THE PSA NOTORIOUS PSA TEST WITH ITS DISASTROUS RESULTS, NOW CONFESSED
BY ITS CHIEF PROTAGONIST DR STAMEY OF U OF CAL......PASS THEM AROUND!!!
1. PSA means Prostate Specific Antigen.
2. PSA is NOT specific and has LITTLE to do with the
prostate specifically.
3. PSA is found in females with breast, lung and
uterine cancers. [whoops!] In fact, the
highest levels of PSA have been found in females RECOVERING from breast
cancers. [J Nat'l Cancer Inst Oct 6, 1999, Fortier, AH et al] Surprise,
surprise, the ladies that made the best recoveries were
the ones with the highest PSA levels!!
4. PSA appears to be an anti-angiogenic molecule. For those of you unfamiliar with the
term, one of the features of cancer is that it has an enormous appetite and
therefore needs a huge blood supply to feed it, so wherever you see cancer
growing, you will see angio-genesis taking place - the
creation of new vascular tissue. [That's why shark cartilage became
popular.]
5. PSA appears to inhibit the usual increases in
circulation necessary to feed the cancer and to support its rapid growth and
proliferation.
6. Nicholas Gonzalez MD of NYC reports patients who have
shown PSA levels of a hundred or more for long periods of time who are doing
just fine as they recover from their cancers - he opines that increased PSA
levels indicates a GOOD response by the body, NOT a BAD response. [audio tapes 12 and 17 spring 1999 lecture, ACAM - see
ordering info below]. Dr Gonzalez uses the nutritional protocol that he
learned from his teacher, the orthodontist and scientist, Dr William Donald
Kelley of Grapevine, Texas, who is one of my three nominees for the Nobel prize
in medicine [along with George J Goodheart DC and
James Pershing Isaacs MD]. Gonzalez also reports a well recovered cancer patient
with a CEA of 350,000, the highest in medical history. See the article on this
site entitled, The AMAS test, to learn about the CEA which is another cancer
marker. When a tumor breaks down it dumps CEA into the blood stream which can be
measured.
WARNING AND CAUTION NOTE!! BE CAREFUL ABOUT WHAT YOU THINK
ABOUT BLOOD TEST LEVELS AND TUMOR SIZES, MORE IS OFTEN NOT WORSE, AND
BIGGER, [TUMOR], IS OFTEN NOT WORSE!!! The healing process
often causes tumors to encapsulate and get a little bigger rather than smaller,
although the growth is stopped and they are walled off!!
7. So giving a toxic drug for a "specific" antigen which
is not at all "specific" is just one more in a long line of examples of medical
quackery being propagated by present establishment sources. It's sort of like giving a deadly drug for a non
infectious, non transmissible disease [AIDS] allegedly caused by an unproved
virus [HIV]. It can also be compared to injecting newborn babies with foreign
proteins and heavy metal poisons to "protect" them from adult diseases found
mainly in intravenous dope addicts [recreational drug users].
Note that I use the old familiar term for these human wastrels - "dope
addicts" rather than "substance abusers" - dope addict is more apropos. Sort of like calling a bum a bum, rather than a homeless
person. Using the euphemism "homeless person" might make you feel better
but hey, life is not fair, some people are bums. Face it. Others are criminals.
Face it. Not facing it results in what we're discussing here. Highly educated people committing crimes against humanity and
getting away with it largely because we indulge the use of politically correct
language. If we were in the habit of calling bums what they are, and dope
addicts what they are, we might not find it so difficult to call an MD a quack
and a criminal and begin to take steps to put them where they belong, behind
bars, not out on the street preying on the innocent and the
ignorant.
The very highly educated, brilliant doctor, Thomas Stamey published the original study on PSA in the
New England Journal Of Medicine in 1987. He concluded, based upon his knowledge,
experience and training along with the study result that the worse the Prostate
cancer, the higher the PSA. Exactly the opposite is true! Dr Stamey is an honest fellow though, he recently was quoted as
saying "I removed a couple of hundred prostates I wish I hadn't." [F.B.Dunn, J Natl Cancer Inst Vol 94, No6, pp 415-16 Mar 20, 2002]
The activities of Dr Stamey
raise several questions:
1. Do you think that Dr Stamey
should be held accountable for those unnecessary surgeries?
2. What do you think would happen to the tobacco industry
executives or the auto industry executives or the toy industry executives if
they were caught killing, maiming or harming so many people - especially
innocent children like those suffering from quack vaccine induced disabilities
and death?
3. Do you think the deaths of prostate cancer patients
resulting from misdiagnosis and maltreatment became part of the statistics used
to place the practice of orthodox medicine in third place on the list of causes
of unnecessary deaths in the
USA?
4. Are you beginning to get the right idea about the
dreadful effects orthodox medicine in the 21st
century?
5. Why is it that many people are serving prison sentences
for shaken baby syndrome [many of whom are victims of medical misdiagnosis] and
doctors are quick to charge lay people with neglect and abuse but we see no
doctors serving time for the same reasons? Since 328 people are killed every day
by orthodox medical activity, why do we not see a lot of doctors in jail? Isn't
it time we began holding them responsible in the same manner they hold lay people responsible?
I'll say it once again, CONSENSUS-DRIVEN, ORTHODOX
MEDICINE IS CRIMINAL BEHAVIOR, IT IS BAD FOR YOUR HEALTH AND IT IS THE
ROOT SOURCE OF ALL OF THE MEDICAL QUACKERY OF THE 21st CENTURY. It is
also the greatest threat to life and limb and health in all recorded history. Do
you REALLY think that orthodox medicine is only number three in the cause of
deaths in the
USA?
If you believe that I have a bridge to sell you! Most of the deaths caused by
orthodox medical doctors go unreported and unrecognized for what they are. The
reported figures are only the tiny tip of a very large iceberg. This
underreporting is especially true of vaccine reactions. Especially in infants
and young school aged children.
And we want to trust these people and accept what they
have to say about VACCINES and HRT [hormone replacement therapy] etc.??? We want
to trust these consensus driven quacks to inject our neonates with poisons? We
want to accept the dribble and gobbledook nonsense
they continue to propagate about vaccines, phantom diseases, phantom viruses,
bacteria and prions as the CAUSES rather than the
RESULTS of most disease processes???
CRISIS MEDICINE, ON THE OTHER HAND, IS A BLESSING TO
HUMANITY - IT WILL SAVE YOUR LIFE IN AN EMERGENCY, RESCUE YOU FROM
CONGENITALLY INFLICTED PROBLEMS, AND SPARE YOU MOST OF THE UNNECESSARY PAIN AND
SUFFERING FROM TRAUMA AND ACCIDENTS - don't confuse one with the other, don't
throw the baby out with the bath water.
WHAT TO DO IF YOU HAVE A SWOLLEN PROSTATE THAT INTERFERES
WITH URINATION:
- Find a doctor who will teach you how to catheterize
yourself.
- Catheterize yourself three times a day to prevent
buildup of urine in the bladder.
- This has been reported to have successfully corrected
an enlarged prostate recommended for surgery. Self catheterization gives the
prostate a rest, allowing it to recover. Saw Palmetto taken on a daily basis
helps the situation.
- Urine buildup in the bladder can be dangerous, be sure
that your doctor monitors your progress.
PASS THIS ON TO AS MANY PEOPLE AS POSSIBLE, ESPECIALLY
YOUR LEGISLATORS.
ORDER THE GONZALEZ AUDIO TAPES FROM:
Anthony Crum Professional Audio
Recording 4905 Marshall Creek
Dr. La
Verne CA
91750 800-430-4727
Dr. Gonzalez's talks are available from the ACAM
Ft.
Lauderdale meeting. Two
tapes are available: a formal lecture tape # 12 and a workshop on a continuation
of the same topic, tape # 17. The order code is 02-102, # 12 &
17. The cost is $11.00 ea. Total $22.00 plus $2.00
shipping, total $24.00. You can place the order by e-mail, fax, or
by phone. Payment is by either credit card. Visa,
Master Card, or AMEX. Or you may send a check to Anthony Crum made
out to PAR.
<!--[if
!supportLineBreakNewLine]--> <!--[endif]-->
*Because of the biased reporting in the USA [polls
reveal that 89% of journalists vote for the democrat party, all three major
networks support the democrat party and continuously under report positive news
and over report negative news of the Republican party, indicating that
journalists as a group are liberal minded, Utopianists
driven by their emotional, rather than their intellectual, brains.] As a result,
the general public is unaware that the liberals proved themselves to be wrong
about the effects of welfare and government support on the lives of the poor.
This was demonstrated by the failure of the NIT [negative
income tax] program - LBJ's pet project designed to
demonstrate that welfare would work if handled properly. In the greatest
social experiment in history two groups were examined: one group received
welfare, one didn't. It was called "the negative income tax program" - it
backfired terribly. LBJ's welfare program tore apart
the negro and hispanic
families in which divorce rates exceeded 80% in one of the groups. All of the
statistics and complete explanation can be found in
Murray's book, Losing Ground, published back in the early 80s. and totally ignored by the liberal establishment].
In the New
Jersey experimental group, the government
supported group showed a divorce rate increase of 66% amongst blacks and an
amazing 84% increase amongst Hispanics!!! The divorce rate amongst whites
remained unchanged.
In the
Gary,
Indiana group there was no
change in the divorce rate because they thought they would lose their welfare
money if they split up.
This controlled program demonstrated the effects of
welfare and should have been widely publicized. It was not. It was stifled and
suppressed by both government and liberal media journalists.
Just as "the dog returns to its vomit", so do
emotionally driven, pseudo intellectual liberals, return to the
socialist experiment which has failed miserably time after time after time
throughout history. You can teach a man how to fish but once you begin giving
him fish, he will never learn to fish for himself and he will then become an
albatross around his neighbor's neck.
DHD Sr rewritten August 12,
2004
THE GREAT THYROID SCAM
By Daniel H Duffy DC
NOTE: LUGOL'S SOLUTION IS AVAILABLE FROM THE GENEVA
CHIROPRACTIC CLINIC - ONE OUNCE DROPPER BOTTLES, $10 EACH, FOUR BOTTLES WITH ANY
SINGLE ORDER FOR $30, plus UPS charges. 440-466-1186.
Isn't it odd that the
government dispenses Iodine to protect against radioactive Iodine resulting from
a nuclear disaster when the medical quacks are dumping the same type of
radioactive Iodine into patients with thyroid problems in a stupid attempt to
"cure" thyroid "disease" caused by a lack of elemental Iodine in its natural
state found in nature?
Nature's Iodine
protects our thyroid glands from taking up biologically destructive, radioactive, Iodine, yet the medical quacks use similar radioactive Iodine
to destroy our thyroid glands??!! [mainly in women].
Why did doctors quit
using Lugol's solution, the sure cure for thyroid
disease? Why did the medical quacks bring in anti thyroid drugs and goitrogens to kill the thyroid gland when Iodine was being
used so successfully for so long? Since Thyroid disease is caused by
malnutrition or poisoning [as are most diseases - if you believe otherwise you
need to read elsewhere on this site to relieve yourself of the "infectious"
disease ideas you carry around in your head.], why is this malnourishment NOT
addressed? How many doctors even know what the [totally inadequate] RDA for
Iodine is, much less that it has never been established by proper studies? And
how many doctors busily destroying female thyroids with quack anti thyroid
remedies know that the Japanese mainlander consumes a hundred times more Iodine
than the American citizen while enjoying the lowest cancer rate of all cancers
except stomach and almost no fibrocystic disease of the breast.
The very term, anti
thyroid, gives one pause?? Why would we want to be "anti" any gland in our
body???
Most importantly - when
will this drug industry driven endocrinological
carnage stop? When will the public wake up and begin to bring the government
sponsored medical quacks to justice to make amends for the terrible damage they
have wrought - especially to our women and children particularly? If the tobacco
industry and the corporate criminals cooking the books of large companies such
as ENRON can be brought to justice, why not the medical goons and their drug
company co-conspirators that are busily crippling and killing our loved
ones??
A hint of the widespread,
mind boggling damage being done daily by drug industry driven medical quacks is
given by a very talented medical researcher in the June 2004 issue of THE
ORIGINAL INTERNIST. In his article entitled "The Concept of Orthoiodosupplementation and Its Clinical Implications" Guy
Abraham MD, wrote, "...medical
textbooks contain several vital pieces of MISinformation [emphasis added] about the essential
element Iodine, which may have caused more human misery and death than both
world wars combined." [8,9] In other
words, the medical scandal concerning the simple and recommended use of iodine
in the form of Lugol's solution vs radioactive iodine and harmful goitrogens has resulted in more misery and death in the last
50 years than that attributed to the two big wars.
8. Abraham, GE. "The Wolf-Chaikoff effect of increasing
Iodide intake on the thyroid." Townsend Letter, 2003;
245:100-101.
9. Abraham, GE. "The safe and effective implementation of orthoiodosupplementation in medical practice." The
Original Internist, 2004; 11(1):17-36.
In the brilliant series
of articles by Dr. Abraham and his fellow researchers I have deduced
the following:
1. The recommended
daily requirement [150 micrograms] of iodine has never been properly
established.
2. The minimum daily
requirement is actually about one hundred times the 150 micrograms
recommended by medical authorities. Japanese consume 13.8 milligrams and
more a day and suffer low breast cancer, fibrocystic breast disease etc. [U of
Pa is now conducting studies on the effectiveness of iodine in breast
cancer].
2. About a third of the
world's population is iodine deficient.
3. Establishment
medical quacks substituted dangerous and destructive quack remedies in the form
of goitrogens and radioactive iodine to "burn out" or
"shut off" thyroid gland function.
4. These same quacks
blamed symptoms described as "iodism" [too much
iodine] on levels of elemental iodine when in fact that they were caused by the
MOLECULAR iodine in their biologically poisonous, goitrogenic, compounds.
5. That there was clear
evidence of chicanery on the part of the researchers in the development of
prescription drugs to replace simple, effective
therapy.
6. The substitution of
Bromine for Iodine in bread dough in the 1960s was probably the final stroke of
bad luck for consumers in regards getting enough iodine in the diet to maintain
proper thyroid function. [along with the addition of
iodized salt]. We have medical authorities, members of the junk food industry
and criminally negligent legislators to blame for
this.
7. In spite of the big
clue published in JAMA, 238:1124, 1976 by Ghandrakant
et al, Breast Cancer. Relationship to Thyroid Supplements for
Hypothyroidism. Medical quacks insisted upon prescribing thyroid hormone
to drive iodine deficient thyroid glands to function at higher levels - they
even went so far as to prescribe synthetic hormone, SYNTHROID while disregarding
the natural, more efficient, Armour brand already
available and productive of far less destructive
results.
8. It doesn't take a
rocket scientist to figure out why we had such a sudden increase in breast
cancer in this country. The increases in all the degenerative diseases can be
laid right at the doorstep of modern medicine, especially when you factor in the
disastrous effects of the use of hormone replacement therapy [HRT] and the use
of Estrogen [the only known cause of breast cancer] and the distortion of
natural Progesterone in favor of the patent medicine Progestin marketed as Progesterone that killed so
many of our young women [strokes] back in the sixties. Any high school student
wishing to take the time to do the research can come up with all the evidence
necessary to prove this point. Indeed, I would recommend any high school student
who happens upon this article to make the attempt. Who knows? You might become
the hero of the 21st century!!!
With such obvious and
blatant quackery being indulged in our country with its mind boggling and
tremendously underrated effects, one can only wonder about the activities of men
such as Stephen Barrett MD and his MD friend Baratz
who expend a lot of their time and energy attacking my profession and my
discipline [Applied Kinesiology] while ignoring the deadly effects of what is
being wrought in their own house. The world would be a better
place if they would tend to their own "dirty linen." They can
be assured that I will continue to publicize the misdeeds of their profession at
every opportunity.
The time for justice
is long overdue in the case of organized medicine, their drug cartel financiers
with their lobbyists and the legislative stooges who live off the drug money
that provides political campaign donations.
I hope that this article
will supply a little more ammunition for the gun that will eventually blow them
all out of the water.
In reading the below
facts keep in mind the effects of all the halogens in our environment that
interfere with Iodine - 1. fluorine in drinking water,
2. chlorine in drinking water, 3. chlorine in swimming pools, 4. Bromine in dough conditioners
[Iodine in flour dough was replaced by Bromine in the 1960s], 5. manmade sources of goitrogens in
pesticides and medicines.
When we add to the above
list the hidden protein loss caused by the displacement of proteins forced to
give up their sulfur to detoxification processes, we see possibly the
greatest and most overlooked effects of such chemicals, the protein
deficiency. In my experience , it is the rare
degenerative or infectious disease that occurs in the presence of adequate
dietary protein, indeed, many of the so called infectious diseases such as
Tuberculosis have been known for decades to be protein deficiency diseases, a
fact that is kept from the public in order to facilitate the sale of vaccines,
antibiotics and other life and health threatening products.
To give an example of the horrendous undercover effects of the great
medical quackery, who could measure the disastrous effect on the public health
by a simple thing such as convincing people that eggs are bad for them? With one
foul swoop a large percentage of the population decides to eliminate eggs from
their diet, denying themselves the very protein and sulfur needed to protect
themselves against the hidden dangers lurking in their environment, not the
least of which is the practice of orthodox medicine.
A recent series of
brilliant articles by Guy Abraham in the pages of THE ORIGINAL INTERNIST
reminded me of one of the first lessons I learned from a fellow chiropractor,
Vince Kulka, after opening my clinic doors in 1972 -
the use of Iodine at hundreds of times the RDA and the use of the Iodine patch
test [rubbing iodine on the skin to observe absorption time]. I was immediately
successful back then in "melting" several goiters which seemed to be prevalent
in this [heavy cow's milk consuming]
dairy community of Ashtabula county. [most of the family
dairies have since closed down].
The purpose of this paper
is to present to busy readers, in briefest form possible, a list of facts with
references from my readings, pertinent to THYROID FUNCTION and IODINE metabolism
- including the overlooked related diseases such as breast cancers, ovarian
cysts and the lumpy breast syndrome [fibrocystic breast disease], a frequently
found condition that continually pops up in the clinic these days which serves
as a constant reminder of the need for IODEX topically and Iodine internally.
I have been using IODEX,
an iodine containing paste applied directly to the skin for the past thirty two
years to help break up the intercostal pain and palpatory soreness at the sternum often suffered by a high
percentage of Midwesterners, especially female hypothyroids. I was taught early
on that Iodine loosens, Iron tightens, Bile dries and
that the Ovary is uniquely involved with Iodine metabolism and that a balance
must be maintained between thyroid hormone and estrogen. I was also taught early
on that it was common practice for veterinarians to rub IODEX on the fetlocks of
horses to eliminate cystic formations. Women are instructed to rub IODEX into
the sore spots at the intercostals at bedtime until the soreness disappears
[wear old nightclothes to protect against the staining of bedsheets] or to use it similarly during the day if
possible.
Ohio seems to continue to be a low Iodine intake region.
Early studies demonstrating the effects of large doses of Iodine were performed
on school children in Akron, a few miles south of my office, during the 1920s.
The need for high doses of Iodine was known then - it was only the abuses
involving FDA, AMA and the alphabet soup medically driven bureaucracies that
brought about the misinterpretations, bad judgement
and reductionist thinking resulting in what Dr Abraham
describes as "iodophobia".
Mainland Japanese consume
a hundred times the amount of Iodine that North Americans do. The coastal
Japanese consume even higher amounts. RDA in this country has never been
established by a scientific study. Recommended RDA in
America is 150μg - Japanese consume 13.8mg! [end of comments]
The two short paragraphs
below were received from a lady website visitor with a large lump in her breast.
She is under the care of an alternative medicine doctor. [emphasis added]
http://www.helpmythyroid.com/IOD1.htm Guy
E. Abraham M.D., Jorge D. Flechas M.D., and John C.
Hakala R. Ph.
"In the 19th edition of
Remington's Science and Practice of Pharmacy,
published in 1995, (11) the recommended daily oral intake of Lugol 5% solution for I supplementation was 0.1-0.3 ml. This
time-tested Lugol solution has been available since
1829, when it was introduced by French physician Jean Lugol. The 5% Lugol solution
contains 50 mg iodine and 100 mg potassium iodide per ml, with a total of 125 mg
I/ml. The suggested daily amount of 0.1 ml is equivalent to 12.5 mg of I, with 5 mg iodine and 7.5 mg of iodide as the potassium
salt. This amount of I is very close to 13.8 mg, the estimated daily intake of I
in Japanese subjects living in
Japan,
based on seaweed consumption."
From Dr.
Derry: "Lugol's solution is an
iodine-in-water solution used by the medical profession for 200 years. One drop
(6.5 mg per drop) of Lugol's daily in water, orange
juice or milk will gradually eliminate the first phase of the cancer development
namely fibrocystic disease of the breast so no new cancers can start. It also
will kill abnormal cells floating around in the body at remote sites from
the original cancer. Of course this approach appears to work for prostate cancer
as prostate cancer is similar to breast cancer in many respects. Indeed, it
likely will help with most cancers. Also higher doses of iodine are required for
inflammatory breast cancer. As well we know that large doses of intravenous
iodine are harmless which makes one wonder what effect this would have on
cancer growth.
I hope this helps you understand breast cancer
better."
Dr. David
Derry http://thyroid.about.com/library/derry/bl1a.htm
IODINE METABOLISM -
THE FACTS
1.
Iodine is the only trace mineral
used to synthesize hormones. J Clin Endocr and Met 1998; 83:3398-3400
2.
Iodine is the most deficient trace
mineral in the world. 1/3 of all peoples are deficient. J Clin Endocr and Met 1998;
83:3398-3400
3.
Iodine deficiency is the number one
cause of underfunctioning intellect. J Clin Endocr and Met 1998;
83:3401-08
4.
The normal daily requirement of
Iodine has never been determined. The Original Internist Dec 2002.
p30
5.
Reports on Iodine poisoning are
misinterpreted, misunderstood and misrepresented to doctors and the lay public.
One medical authority of wide influence, R. Arem MD,
incorrectly reported [The Thyroid Solution..." 1999]that
high Iodine intake caused increases in thyroiditis and
thyroid cancer in Argentina. Just the opposite was true, low Iodine contributes to
thyroid cancer. One archived anecdotal case from Dr Arem reported that 2.3 grams of Kelp/day caused Grave's
disease necessitating thyroid gland destruction. Japanese consume 4.6 grams of
seaweed per day and continue to be amongst the world's healthiest peoples. Arem unfortunately advises Iodine consumption be restricted
to only 500 to 600 μg/day micrograms/day. The
Original Internist Dec 2002 p30, 31.
6.
15% females are Iodine deficient
with urine levels less than 50 μg/L exposing them to prescription thyroid
hormones by doctors who never check urinary Iodine levels. J Clin Endocr and Met 1998;
83:3401-08.
7.
Iodine works better than the
hormones and lasts twice as long when discontinued. Eur J Clin
Inv 1989; 19:527-534.
8.
Iodine deficiency predisposes to
breast cancer and high fat diet predisposes to Iodine deficiency. J Epid Comm Health 2000;
54:851-858.
9.
Japan and Iceland have high Iodine
intake and low goiter and breast cancer, just the reverse occurs in
Mexico and Thailand. Quart Rev Surg Obstet Gynec, 1960;
17:139-147.
10.
Iodine protects against estrogenic
effects in breast cancer. JAMA 1967; 200:115-119, Adv Exp Med Biol,1977; 91:293-304.
11.
Thyroid hormone therapy contributes
to breast cancer in Iodine deficient women. JAMA ,
1976; 238-1124.
12. In the usually misleading establishment organ Cancer,
1964, 17:1174-76 - effects of Iodine deficiency were incorrectly interpreted
based upon goiter incidence in Michigan. Goiters decreased from 38.6%-1.4% between 1921 and
1954 with no change in breast cancer. Their mistake was that they presumed
incorrectly that the amount of Iodine needed to prevent goiter would be equal to
the amount to prevent breast cancer. However two studies show that in woman and
female rats it takes 20 to 40 times the amount of Iodine needed to control
breast cancer and fibrocystic disease than it does to prevent goiter. Can J
Surg 1993; 36:453-460, Biological Trace Element
Research, 1995; 49:9-19.
13.
Many drugs contain Iodine. Bad Side
effects of Iodine containing drugs are usually blamed on the Iodine they contain
without ever submitting the hypothesis to a study. Good effects are attributed
to the drug. The Thyroid, Werner & Ingbar, Lippincott 2000 316-329.
14.
Amiodarone is an antiarrythmia drug that
contains 75 mg Iodine per 200 mg tablet that releases 9mg/day Iodine/day. 20% of
users of Amiodarone develop hypothyroidism. It also
causes destructive thyroiditis for which large amounts
of glucocorticoids are prescribed or occasionally,
thyroidectomy. The authors Roti and Vagenatis [The Thyroid
above] blame the Iodine for the side effects. Japanese actually consume 13.8 mg
Iodine daily and enjoy one of the lowest incidences of hypothyroidism and Iodine
deficiency goiter. Quart Rev Surg Obstet Gynec, 1960;
17:139-147.
15. The
widely read textbook on Thyroid Werner and Ingbar's,
The Thyroid, edited by Braveman and Utiger, Lippincott 2000 contains a subsection in which Iodine is
identified as a pathogen. Title of the article is "Iodine As A Pathogen" and daily intake above 500 μg is considered excess, an amount equal to only 3% of the
daily intake in Japan, a country with extremely low female reproductive organ
cancers. Int J Cancer 1986, 38:325-329 Japanese
mainlanders consume 100 times more Iodine than Americans and coastal Japanese
consume higher amounts than the mainlanders.
16.
Thiocyanate is a goitrogen and
caused hypothyroidism in rats on regular RDA amounts of Iodine. The effect of
the goitrogen was eliminated by increasing the rat
Iodine intake to 80 times the RDA. Hormone & Metabolic
Res 1995 27:450-454.
17.
When Iodine was used in dough during
the sixties one slice of bread a day contained the RDA of 150 μg and the breast cancer risk was 1:20. The use of Iodine in bread dough was replaced with the
goitrogen Bromine based upon ill conceived, reductio absurdum results of lab driven reductionist medical methods. due
to stupid medical reductionist thinkingmedical stupidity and the rate of breast cancer has
soared to 1:8 and is increasing at 1% a year.
18.
Prescribing thyroid T4 to
hypothyroids increases susceptibility to breast cancer. JAMA 1976;
238:1124.
19. To
overcome the effects of goitrogens in the food chain
such as Bromine in dough, amounts of Iodine used in
Japan would be necessary. Hormone &
Metabolic Res 1995, 27:450-454.
20.
The last common food source for
Iodine in the USA is iodized salt and the stupidity of medicine surfaces again
as the prestigious J of Clinical Endocrinology and Metabolism recommends cutting
DOWN the amount of Iodine in salt to half the amount now present! The title of
the article is "Guarding our Nation's Thyroid health".
21.
The percentage of thyroidal uptake
of Radioactive isotopes of Iodine from nuclear
catastrophe is increased in areas of severe endemic goiter reaching levels of
80%. Am J Clin Nutr 1974, 27:96-103.
22.
Iodine protects against uptake of
the radioactive isotopes of iodides. The more Iodine consumed in the diet, the
lower the percentage of uptake of radioactive isotopes by the thyroid
gland. Werner and Ingbar's, The Thyroid, edited by Braveman and
Utiger, Lippincott 2000,
295-329.
23. At
Iodine RDA levels of 150 μg, uptake of radioactive
Iodine is 20-30% of intake. When Iodine was introduced into bread dough in the
sixties the Iodine intake increased 4 to 5 times the RDA and the Iodine uptake was decreased to
below 20%. NEJM 1969;
280:1431-1434.
SUMMARY
Orthodox medicine,
throughout recorded history has used a wide variety of substances and surgical
techniques in an attempt to relieve pain and suffering, to fight disease and to
improve health. As a result, the practice of crisis medicine,
greatly facilitated by technological rather then medical progress, has rescued
us from congenital problems, accidents and trauma, however,
statistically, the practice of patent medicine more than
cancels out all benefits gained by technological advances.
The practice of
orthodox medicine is a life threatening, health robbing enterprise
of mind boggling proportions having absolutely unbelievable effects on life and
health - exactly opposite that which is portrayed daily on television and in the
popular news media.
For every patient helped by
crisis medicine some unknown but more than likely, mind boggling number, are
worsened and even killed outright [E.g.: 11,000 victims of the SMON "epidemic"
in Japan during the 50s and 60s; thousands of Swine flu vaccine victims during
the 70s; thousands of US victims killed by AZT during a
similar medical crime during the 80s and 90s AIDS fiasco; more recently 80
[known and publicly admitted] victims of Baycor, the
Bayer Aspirin company's cholesterol reducing drug; and most recently, thousands
upon thousands of [mostly unreported] infants and schoolchildren victims
of mercury poisoning from totally unnecessary and extremely destructive vaccines
especially during the 90s.]
I would estimate that for
every patient helped by crisis medicine at least a hundred or more are killed,
maimed, momentarily or irreversibly damaged by biological poisons. I just lost a
long time patient who had moved to Florida after retiring. He started on LIPITOR after
departing from our influence and died unexpectedly of a heart attack. A very vigorous, family oriented man who should have lived to be 90
or more.
The painfully evident
statistical fact is that humanity would be far better off without an
organization of doctors and no free country can long survive the intrusion
of government in medicine and especially, an organization of
doctors wielding government power.
We can learn from our
mistakes and experience but not when governed by a group of self appointed
protectors [AMA, FDA, CDC, NIH] who continually interfere with the propagation
of knowledge useful to health and most importantly, PREVENT THE LEARNING
FROM TAKING PLACE.
Improvements in health
attributed to medicine have been gained by improving the tools of production and
improvement in other forms of technology such as 18 wheelers that deliver fresh
foods during all seasons regardless of weather [the direct result of which is a
continual decrease in the number of diseases [incorrectly] labeled as
"infectious" by "bug happy" doctors].
Other small improvements in
health and longevity can be attributed to what medicine has STOPPED doing rather
than BEGUN. Bloodletting is one example, another, the elimination of the
especially poisonous old remedies such as CALOMEL the escape
from which unfortunately only lasted until mercury was again used in vaccines
under the label THIMEROSAL which faked out even the pediatricians using it on
newborn infants, bringing about the most horrendously sudden increase in
iatrogenic disease in all recorded history. Government statistics show that
Cases of Autism have increased several thousandfold in some areas of the country.
Indeed, careful
investigation, reevaluation and reinterpretation of historical evidence demonstrates that the poor health of the nation and for that
matter, the entire world can be laid directly on medicine's
doorstep.
The evidence does
demonstrate that doctors do, in fact, kill more people than generals and wars.
Only a small percentage of the population is aware of this at any given time in
history which explains why doctors continue to enjoy their self appointed
position as the guardians of health.
Dr Daniel H Duffy Sr
May 27,
2004
Rewritten August 12, 2004
LUGOL'S SOLUTION IS
AVAILABLE IN TABLET FORM in Lugol's original ratio of
iodine to iodide.
Call 1-800-223-1601 - ASK
FOR IODORAL...professional discounts for quantity orders are
available.
WANT TO KNOW IF YOU'RE
IODINE DEFICIENT??
SEND FOR DR FLECHAS'S 24
HOUR URINE TEST FOR $75. A test dose of iodine is taken followed by a 24 hour
collection of urine - normal excretion is 90% of test dose.
Jorge D. Flechas, M.D.
#80 Doctors
Drive Suite 3
Hendersonville,
NC
28792
Office: (828)
684-3233
Fax: (828)
684-3253
Email: helpmythyroid.com">drflechas helpmythyroid.com
Effect of daily ingestion of a
tablet containing 5mg Iodine and 7.5mg Iodide as the potassium salt, for a
period of 3 months, on the results of thyroid function tests and thyroid volume
by ultrasonometry in ten euthyroid Caucasian Women.
Guy. E.
Abraham M.D., Jorge D. Flechas M.D., and John C. Hakala R.Ph., The Original
Internist 9: 6-20, 2002
Iodine sufficiency of the whole
human body
Guy. E.
Abraham M.D., Jorge D. Flechas M.D. and John C. Hakala R.Ph., The Original
Internist 9: 30-41, 2002.
Effect of daily ingestion of Iodoral
Guy. E. Abraham M.D., Jorge D. Flechas M.D. and
John C. Hakala R.Ph.
The Wolff-Chaikoff Effect: Crying Wolf?
Guy E.
Abraham, M.D.
More to come later
A MORE TECHNICAL ARTICLE
Measurement of urinary iodide levels by ion-selective
electrode: Improved sensitivity and specificity by chromatography
on
anion-exchange resin.
Guy. E. Abraham
M.D.1, Jorge D. Flechas M.D.2
and John C. Hakala
R.Ph.3
I.
Introduction
The last national nutritional survey (NHANES III 1988-1994)
revealed that 15% of the
U.S. adult
female population are iodine-deficient, as defined by
the World Health Organization: levels of iodine/iodide (I) below 50 ug/L (1). That is one out of
every 7 female patients walking in a physician's office. Yet,
rarely do physicians order urine I levels, even in patients with simple goiter
and hypothyroidism. Such patients are usually prescribed
thyroid hormones. There is convincing evidence that I
deficiency predisposed to fibrocystic disease of the breast (FDB) and breast
cancer (2-8). Administration of thyroid hormones
to I-deficient women increased further their risk of breast cancer
(9). Forty years ago, the risk ratio for breast
cancer in our population was one in twenty and now it is one in eight
(10), coincident with an increased prevalence of I deficiency in our
population (1).
To encourage physicians to perform routine urine I
determination in their practice, a simple method will be described to accurately
measure urine I levels. This technique uses quantification of
iodide by a potentiometric method, using an
ion-selective electrode (ISE). Urinary iodide is measured by
the electromotive force (EMF) generated on the iodide-selective electrode due to
the presence of iodide in the urine sample. Within a certain
range of iodide concentrations, there is a linear relationship between the
logarithm of iodide concentration and the EMF generated. The
concentration of chloride in urine is usually one millionfold higher than iodide and there is a significant
interference by chloride in the analysis of urinary iodide by the ISE
method. To prevent this interference, purification of the
urine sample by anion exchange chromatography is performed prior to ISE
measurement. This assay is simple, rapid, with results within
one hour, if the ISE measurement is performed in the physician's
office. We also present preliminary data on an I-loading test
to assess I sufficiency of the whole human body.
II.
Motivating factor in the
development of the assay
Mainland Japanese women have a very low incidence and
prevalence of FDB and breast cancer (11). Several
investigators have proposed that the essential element I was the protective
factor in mainland Japanese (2-8). If indeed, the
essential element I is the postulated protective factor, the administration of I
to American women in amounts equivalent to that consumed by mainland Japanese
women would be expected to protect them from breast cancer and improve FDB, as
previously proposed by Stadel for breast cancer
(12) and confirmed for FDB by Ghent et al (5).
Based on data supplied by the Japanese Ministry of Health, the average
daily I intake in mainland Japanese is 13.8 mg
(13).
We evaluated the effect of 2 drops of Lugol solution in tablet form containing 5 mg of iodine and
7.5 mg iodide as the potassium salt, (Iodoral(r), Optimox
Corporation, Torrance, CA), administered daily for 3 months to 10 normal
women. Informed consent was obtained from all subjects
participating in the studies described in this manuscript.
This supplement had no adverse effect on ultrasonometry of the thyroid gland, the serum levels of thyroid
hormones, blood chemistry, hematology, and urine analysis
(13). This form and amount of I was chosen because it was widely prescribed during
the early and mid 1900's for I replacement therapy
(13-16). The amount of 12.5 mg
of I present in 2 drops of Lugol is very close to the
estimated mean daily intake of 13.8 mg I by mainland Japanese (13).
4 5l 4 11 9 11 9 5xe" filled="f"
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According to the medical literature, urinary I level is the
most valid index of I intake (17, 18). Using a
commercial laboratory (Doctor's Data Inc.,
Chicago,
Ill.), we followed the pattern of 24 hour
urinary I excretion before and after ingestion of one tablet of Iodoral(r) in 2 male and 3 female
subjects. To our surprise, both male and female subjects who
ingested one tablet of Iodoral(r) containing
12.5 mg I, excreted in their 24 hr. urine samples only 10 to 30% of the I ingested, with a mean of 20% (Table I).
There are two possible explanations for this finding: Low bioavailability
of the solid dosage form of the I tablet; or high
retention by the body. If this was due to low
bioavailability, prolonged administration of this I supplement should not result
in an increased urinary excretion; otherwise, as the body becomes more
I-sufficient, a greater percentage of the ingested I would be
excreted. In order to elucidate the cause of this low I
excretion, we continued the administration of I in those subjects for one
month. Then, we repeated the 24 hr. urine collection and I
was measured again in the collected urine samples.
<!--[if !vml]--> <!--[endif]-->
Following one month of daily ingestion of one tablet of Iodoral(r), the excretion of I increased to 36-96%
of the oral amount in 4 of the subjects
with a mean of 50% in the 5 subjects (Table I). Female
Subject #2 excreted only 10% of the oral dose after one month of
supplementation. She had the lowest baseline I level (0.022
mg/24 hr) and the greatest I retention after one and 30 days. The only
distinctive feature of this subject was mammomegaly
(size 40D). This would suggest a very important role of the
mammary glands in the requirement for I by the whole
human body. To our knowledge, the above findings have not
been previously reported. The implication of such observation
is that an I-loading test could be developed to assess not just thyroid
sufficiency but I requirement of the whole human body.
However, for such a test to be practical, one month duration is too
long. So, the next alternative was to progressively increase
the amount of I in a single dose and to measure urinary I excretion in order to
find the amount of ingested I that would result in the greatest between
individual differences of urine I levels, as an index of degree of whole body I
sufficiency. The standard deviation from the mean value could
be used as an index of the between-individual
variations.
Another group of 6 subjects, 3 males and 3 females were
evaluated with 24 hour urinary I levels before and after ingesting one, two and
three tablets of the same preparation. The subjects retained
approximately 80% of the I content of one and two
tablets (Table II). But with three tablets containing 37.5 mg
of I, there was a twofold difference in I excretion, with a range of 6.8 to 14
mg I (18%-37%) (Table II).
The means ± SD of urinary I levels (mg/24 hr.) for the 3
doses of I were: 2.8 ± 0.14 (C.V. = 5%) for one tablet of Iodoralâ; 5.4 ± 0.35 (C.V. = 6.5%) for 2 tablets; and 9.48
± 4.6 (C.V. = 48.5%) for 3
tablets. There was a 10 fold increase in the coefficient of
variation around the mean value at 3 tablets of the I supplement,
compared to one and two tablets. Subject #3 who retained the
most I, with only 6.8 mg (18%) in the 24 hour urine collection, suffered
from severe FDB, again pointing at the mammary glands as an important organ of I
utilization. These results suggest that the measurement of
urinary I levels before and after administration of three tablets of Iodoralâ, could be used as an I loading test to assess
I sufficiency of the whole human
body.
<!--[if !vml]--> <!--[endif]-->
For the I-loading test to be widely used in the physician's
office, the measurement of urine I levels would be best performed in situ, using
a simple method with non-hazardous reagents. The values for I
presented in Tables I and II were obtained by a procedure called Induction
Coupled Plasma-Mass Spectrometry (ICP-M.S.). The equipment
required for this procedure is extremely expensive and very complex in their
utilization. The ISE method is very simple, requiring only
the following two reagents: water and sodium nitrate. Sodium
nitrate is used in the ISE method as an Isotonic Strength Adjuster (ISA) at an
initial concentration of 5 Moles/L to improve performance of the ISE
electrode. The ISA is diluted 1 part ISA to 2 parts of iodide
standards and urine samples. The final concentration of
NaNO3 in the assay is 1.66 Molar. The ISE
procedure does not require any special precaution, beside the usual good
laboratory practice. Water and NaNO3 are used in
the ISE measurement and in the chromatographic purification of urine samples on
anion-exchange resin, simplifying the procedure.
III.
Measurement of iodide in biological fluids by ion-selective electrode:
A review of pertinent publications.
A) Urinary
iodide
In 1983, Cooper and Croxson
(19) wrote a "Letter to the Editor", published in the Journal of
Clinical Chemistry, describing their unsuccessful attempt to measure urine
iodide levels in New Zealanders by the direct ISE method, using equipment from
Thermo Orion, Beverly,
Mass.,
USA. The
high concentration of chloride present in urine samples interfered in the
assay. They were unable to achieve reliable and reproducible
results. They postulated that chloride was the interfering
substance due to the persistence of this interference following deiodization of urine by chromatography on anion-exchange
resin. This procedure retained iodide on the column, but
chloride was eluted in the chromatographed
urine. Not only the presence of chloride rendered the assay
non-specific for iodide, but caused also a decrease in sensitivity by one order
of magnitude. With standards of iodide in water, the
sensitivity was 10-6 M (0.127 mg/L), but with standards in deiodized urine, the sensitivity was 10-5 M (1.27
mg/L). It is surprising that these authors did not carry
their experiments to the next logical step: Use the same anion-exchange resin to
purify iodide from chloride. Since chloride was eluted with
the chromatographed urine but iodide was retained on
the column, they could have used a high ionic strength buffer to elute the
iodide fraction afterward. The urinary I levels of New
Zealanders are 10 to 20 times less than the sensitivity of 1.27
mg/L. These authors concluded: "We conclude that, on the
basis of chloride error, the iodide-selective electrode is unsuited for the
accurate experimental determination of iodide in urine."
In 1986, Yabu et al (20)
came to the realization that the New Zealander's problem was not a problem at
all for mainland Japanese. Although they confirmed Cooper and
Croxson's findings that the assay was not specific below 1.27 mg/L, mainland Japanese
excreted higher levels of urinary iodide than 1.27 mg/L.
In 163 urine specimens analyzed, only one specimen had a concentration
below 1.27 mg/L. They observed I levels in these urine samples ranging from 0.6
mg/L to 17.4 mg/L. If those I levels are expressed as mg/24
hr. and assuming an average 24hr. urine volume of 1.5 liter, the range of I
excretion per 24 hr. would be from 1 to 25 mg in these 163 Japanese
subjects. This range is in agreement with the estimated
average daily I intake of 13.8 mg I in mainland Japanese (13).
The iodide levels observed in the mainland Japanese were two
orders of magnitude higher than urinary iodide concentrations in New Zealanders,
for that matter, in citizens of the Western World (13).
In 1993, Kono et al (21) using
direct measurement of urine iodide in 2956 men and 1182 women confirmed the
reliability of the direct ion-selective electrode assay in urine samples from
mainland Japanese subjects. However, Yabu and Kono were not able to
measure accurately iodide levels below 1.27 mg/L, due to chloride
interference. Above that level, they achieve excellent
correlation with an established assay for urinary iodide, the ceric ion-arsenious acid method
(22). It is of interest to note that the electrode
and meter used in the 2 publications from
Japan were
obtained from Radiometer,
Copenhagen,
Denmark.
This company supplies a procedure to perform direct measurement of
urinary iodide with their equipment.
B) Milk
iodide
In 1980, Lacroix and Wong measured
iodide directly in cow milk by ion selective electrode
(23). They reported a value ranging from 0.14 to
0.35 mg/L, when the milk analyzed was taken raw from individual
cows. Market milk contained mean levels ranging from 0.52 to
0.70 mg/L. These authors did not perform experiments to prove
the specificity of their procedure. In 1984, Gushurst el al (24) measured iodide in human milk by ion-selective
electrode. They observed values ranging from 0.029 to
0.45 mg/L. Since the concentration of chloride in milk
is 10 times less than in urine (25), they were able to measure iodide
levels down to 0.029 mg/L. The studies performed with milk
samples used iodide-selective electrode and meter from Thermo Orion,
Beverly,
Mass.,
USA. The
authors of these studies did not confirm specificity of their assay by
comparison with an accepted method.
IV.
Purification of urine samples by anion-exchange chromatography prior
to assay of iodide
For the ISE method to become widely used in the clinical
setting, it must be reliable at all levels of urinary iodide, down to levels
observed in severe I deficiency (<0.025 mg/L). To our
knowledge, a procedure combining prior chromatographic purification to improve
specificity and sensitivity of the ISE assay of iodide in biological fluids has
not been published. In our opinion, purification prior to ISE
measurement is a sine qua non requirement for specificity and sensitivity of the
ISE assay under all physiological and pathological conditions, including severe
I deficiency (urine I <0.025 mg/L). Chromatographic
purification of urine samples on columns of anion-exchange resin was selected
for the reasons described below.
In 1962, Murthy et al (25) reported a procedure
for removing radioactive iodide from milk. A strong anion
exchange resin was used (Dowex 2 X 8) to retain the
radioactive iodide and large volume of milk could be processed through these
columns. A mean ± SD of 98 ± 2% of the iodide could be
retained on the columns when 120 bed volumes were chromatographed. The bed volume is
approximately 1 ml per gm of resin. They were able to elute
approximately 98% of the radioactive iodide from the column with 30 bed volumes
of 2N sodium nitrate (NaNO3) in 0.16N HNO3.
This publication was of great interest to us since the ISE assay of urinary
iodide published by the Japanese scientists (20, 21) used 5 ml of 5N
NaNO3 as ISA, added to 10 ml of urine. We
postulated that by prior chromatographic purification of urine samples on anion
exchange resin and using 5N NaNO3 as the elution solvent to elute
iodide, measurement of iodide could be made directly after adding 2 volumes of
water to the eluant.
Materials used in anion exchange chromatography are composed
of 3 components attached together and placed in a column: the base or backbone
support; the functional group or ion exchanger, and the counter ion available
for exchange. For backbone, styrene divinyl benzene (SDB) was preferred over silica gel because
it is more rugged, less sensitive to pH changes and possesses a higher capacity
(26). For
example, SAX columns with silica backbone are available from Varian and
Associates (Harbor City, CA)
with a capacity of 0.85 m Eq/gm of resin.
However, with SDB backbone, Alltech
(Deerfield,
Ill) quotes a figure of 1.5 m Eq/gm, a 75% greater capacity to exchange
anions. This translates into the ability to process a 75%
greater volume of urine for the same amount of resin.
Strong anion exchangers are quaternary amines versus weak
anion exchangers, which are primary, secondary and tertiary amines.
Strong anion exchangers are always charged at any pH; therefore elution
of the analate of interest
could be achieved by increasing the ionic strength of the elution solvent
without any acid added. Data are available for strong anion
exchangers regarding the relative selectivity of halides (26): With
fluoride as unity; chloride has a relative selectivity of 10; bromide 28; and
iodide 87. The higher the number, the
stronger the binding of the halide to the anion exchanger.
The stronger the binding of the halide to the ion exchanger, the higher
the ionic strength required for elution. Therefore, by
choosing a wash solvent with ionic strength high enough to elute fluoride,
chloride and bromine, but not high enough to elute iodide, a high degree of
purity of the iodide fraction could be achieved.
For counterions, the choice from
products available commercially, was between chloride and acetate.
Since chloride interferes in the assay, we chose the acetate form (Fig.
1). Although a wide range of counterions could be prepared by preconditioning the anion
exchange columns, this would not be practical in a clinical setting. The ideal
counterion on the SAX columns used for the
purification of iodide from the other halides would be nitrate.
Based on information supplied by Alltech with
the SAX columns, iodide is the only halide capable of displacing nitrate from
the tetramethylamnonium group. The
smaller pore size of 60Å was preferable because it excluded molecules with
molecular weight above 1000 and it prevented overloading the resin with high
molecular weight anions present in urine samples. Finally,
the larger particle size was chosen because it allowed elution at the proper
flow rate with lower pressure and vacuum. In Table III are
displayed the various options commercially available for anion exchange
chromatography. The characteristics chosen are in the right
column.
<!--[if !vml]--> <!--[endif]-->
<!--[if !vml]--> <!--[endif]-->
The strong anion exchanger SAX was obtained from Alltech
(Deerfield,
Ill) and tested with bed weights of 100, 200,
500 and 600 mg of SAX. The bed weights of 300 and 400 mg were
not available commercially. This resin has a SDB base with a
functional group of tetramethyl ammonium and with
acetate as counterion (Fig. 1). We
were interested in a column of SAX that had the capacity to handle up to 30 ml
of urine without overload and breakthrough of iodide. The
reason for this will be explained later. Preliminary tests
revealed that 500 mg of SAX was the minimum bed weight required to process 10 to
30 ml of urine without overload (breakthrough) of the column.
Overloading the column resulted in the presence of iodide in the urine
eluate after the first pass, causing low recovery of
iodide in the purified fraction eluted with the high ionic strength solvent.
The 500 mg column with a 10 ml reservoir was chosen (Alltech part #309750). Ten ml of urine
was applied to the SAX column, which was fixed on top of a vacuum manifold
(Applied Separation Inc., Allentown, PA), connected to a vacuum pump (Alltech, Deerfield, Ill). We used the
model # Bench Top Vacuum Station which was
capable of maintaining a preset vacuum. A vacuum of only 2
inches (50 mm) of mercury was sufficient for an elution flow rate of 4-5
ml/min. Due to variation in airflow through the different
openings of the vacuum manifold and variation of elution flow rates between the
columns, there was a twofold difference between columns with the fastest and
slowest flow rate. The elution of 10 ml of urine required 2
to 4 minutes at the vacuum setting of 50 mm Hg.
The 4 halides, fluoride, chloride, bromide and iodide were
added individually in known amounts from stock standard solutions to pooled
urine samples collected from a fasting subject. Using
Thermo-Orion ISE electrodes and special reagents, the halides were measured
following chromatography in the eluted urine, in the wash solvent (10 ml of 0.5N
NaNO3) and in the elution solvent (5 ml of 5N
NaNO3). The standard curves for the 4 halides are
displayed in Fig. 2.
<!--[if !vml]--> <!--[endif]-->The eluted
urine contained fluoride and 75-80% of the chloride. Some
20-25% of the chloride was retained on the column, together with bromide and
iodide. A wash of the column with 10 ml of 0.5N NaNO3
eluted the retained chloride and the bromide.
Quantitative recovery of iodide
(>95%) was achieved with 5 ml 5N NaNO3.
The eluant containing the iodide in 5 ml of 5N
NaNO3 was mixed with 10 ml of water and measured directly by
immersion of the iodide selective electrode (Orion Electrode #9653 BN) connected
to the Orion Meter 720-A Plus. Standards of potassium iodide
(Spectrum Chemical,
Gardena,
CA #P0185) were prepared in water at
concentrations ranging from 10-3 M to 10-8 M.
A volume of 10 ml of iodide standard was mixed with 5 ml of 5N NaNO3
prior to measurement by the iodide selective electrode.
The stored standard curve in the 720-A Plus meter was programmed to
display the urinary I levels in mg/L.
V.
Methodology
Urine samples collected over a period of 24 hr were stored by
the subject during collection in a 3 liter plastic bottle, supplied by Doctor's
Data Inc. After measurement of the total volume at the
clinic, sodium azide was added at a final
concentration of 0.05% for bacteriostatic purpose
(10ml of a 5% solution per liter of urine). Sodium azide is the commonly used bacteriostatic agent in such cases
(20). Prior to addition of the sodium azide, a sample was obtained and mailed to Doctor's Data for
analysis by ICP-M.S. Samples of the collected urine were then
stored at -20º C in plastic containers until assayed by the ISE
method. Repeated freezing and thawing the urine samples had
no significant effect on the measured I levels. However,
without a bacteriostatic agent, such manipulation of
the samples resulted in decreasing I levels and
evidence of bacterial growth. Aqueous solutions of 0.5N and
5N NaNO3 (Spectrum Chemical #SO183) were prepared and stored at room
temperature. A stock solution of potassium iodide 1.66 gm in
1 liter of purified water (10-2 Molar) was stored in a dark glass
bottle. From this stock solution, iodide standards were
prepared by dilution to contain a range from 10-3 M
(127 mg/L) to 10-8 M (0.00127
mg/L).
Under a vacuum of 40 to 50 mm Hg, 10 ml of urine was applied
to a SAX column 500 mg, with a 10 ml reservoir (Alltech #309750) and the elution flow rate adjusted so not
to exceed 4-5 ml/min. This is the most critical step in the
assay. A slower flow rate did not have an adverse effect on
the performance of the anion-exchange columns. Exceeding this
flow rate however, caused breakthrough of iodide in the urine eluate, with low recovery of iodide in the
assay. At the same vacuum setting, the elution flow rate
decreased with the wash and elution solvents. Therefore, it
was very important to set the flow rate during the elution of the urine
sample. Since there was variation in flow rate between the
columns, the SAX column with the highest flow rate was used to monitor visually
the urine level in the reservoir. To facilitate this process
of observing urine levels through the opalescent wall of the reservoir, a food
coloring was added to the urine samples prior to chromatography.
FD & C Green No. 3 (Warner Jenkinson
Company, St. Louis,
Missouri) was selected for its useful
attributes. Having 2 benzene rings in its molecule (Fig. 3),
resulted in a very strong hydrophobic interaction with the benzene rings in the
SDB backbone of the SAX (Fig. 1). FD & C Green No. 3 was
retained on the column, resulting in a clear eluate. Although FD & C Green No. 3
contains a quaternary amine (Fig. 3) capable of binding iodide, its
concentration was so low that no significant interference was observed in the
performance of the columns. We added 1 ml of a 1% solution
per liter of urine. The amount of that dye in 10 ml of urine
was 0.2 µMole, compared to a concentration of 750 µMoles of quaternary amines on
the SAX column. FD & C Green No. 3 has antiseptic,
therefore bacteriostatic properties, since it is used
topically and orally in veterinary medicine as an antiseptic
(27). We are currently testing FD & C Green
No. 3 as a bacteriostatic agent to replace sodium
azide. So far, the results look
very promising.
<!--[if !vml]--> <!--[endif]-->We have
tested several SAX columns with both silica and SDB backbones obtained from
Alltech and Varian. The vacuum
setting required for the proper elution flow rate varied widely between SAX
columns with as much as 15 inches (375 mm) Hg for some SAX columns with silica
backbone and small particle sizes. With the Alltech 500 mg SAX columns, however, a vacuum setting of
50 mm Hg resulted consistently in the proper flow
rate. The Alltech vacuum pump
displayed the ambient atmospheric pressure in mm Hg. The
desired vacuum was achieved by setting the vacuum pump at 50 mm below
ambient.
Chromatography of the urine sample on the SAX column yielded
3 fractions, which were used to measure fluoride, bromide and
iodide. The flow chart in Fig. 4 summarized this
procedure. The eluted urine contains >95% of the fluoride
and 75-80% of chloride. Ten ml of the special ISA TISAB II
(Thermo Orion #940909) was added to the 10 ml of eluted urine and fluoride level
was measured with electrode #9609BN. The wash solvent
consisted of 10 ml of 0.5N NaNO3 and following chromatography on the
SAX column contained 20-25% chloride and >95% bromide.
Using the electrode #9635BN, bromide levels were measured following
addition of 5 ml of 5N NaNO3 to the eluted wash solvent.
The bromide standards used to compute the standard curve were prepared
in
0.5N NaNO3.
Validation of the bromide assay will be the
subject of another report. The last step was the addition of
5 ml of 5N NaNO3 to the column and elution of iodide at the same
vacuum setting, although the flow rate was less, between 2 to 4
ml/min. Ten ml of water was mixed with the eluted 5 ml 5N NaNO3. Iodide
concentration was measured directly by immersion of the electrode (Orion
#9653 BN).
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VI.
Acceptability of the ISE method for urinary iodide
measurement
We followed the same procedure we previously described for
the validation of radioimmunoassay of steroid hormones in biological fluids
(28, 29). The criteria for
acceptability of an assay includes reliability and
practicability. The reliability of an assay depends on its
sensitivity, specificity, accuracy and precision. The
practicability of an assay is judged by the skill required to perform it, the
time involved in its performance and the cost of the assay.
A) Reliability
experiments
1)
Sensitivity
The theoretical limit of sensitivity achievable with ISE
assay of urinary iodide is set by the sensitivity of the iodide selective
electrode itself. From data supplied by Thermo Orion, the
sensitivities of the ISE electrodes for halides are: For iodide, 5 x
10-8 M; for fluoride, 10-6 M; for bromide, 5 x
10-6 M; and for chloride, 5 x 10-5 M.
The iodide selective electrode is by far the most sensitive being 20
times more sensitive than the ISE electrode for fluoride, 100 time more sensitive than for bromide and 1000 times more
sensitive than for chloride. Expressed as mg/L, the iodide
selective electrode is sensitive down to 0.006 mg/L, compared to a sensitivity
of 0.003 mg/L, for ICP-M.S. used by Doctor's Data Laboratories.
(Information on sensitivity of ICP-M.S. supplied by
Dean Bass).
In achieving this theoretical sensitivity, other conditions
are important. First, the sensitivity of the standard curve
is a limiting factor. The sensitivity of the standard curve
is defined as the smallest amount of iodide that is significantly different from
zero at the 95% confidence limit. In order to compute the standard curve, (the
dose response curve) the EMF expressed in millivolts
(mV) was plotted on the Y-axis against the logarithm of increasing amount of
iodide, from 10-3 M to 10-8 M on the X-axis.
The iodide selective electrode was extremely sensitive (Fig. 5), with a
linear response from 10-3 M to 10-7 M.
A mean D EMF of 61
mV per decade was observed from 10-3 M to 10-7 M, but from
10-7 M to 10-8 M, the standard curve became non-linear
with only 36.2 mV per decade.
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To calculate the mean blank value, samples containing zero
iodide are run in the assay using several replicates, ideally 6
replicates. The sensitivity would then be equal to 2 standard
deviations from the mean blank value, after subtracting the mean blank
value. We tested water blanks and deiodized urine blanks. When 6 samples of
water of 10 ml each were chromatographed on the SAX
column as described under methodology, we obtained a mean ± SD of 0.0024 ± 0.0006 mg/L.
Deiodized urine was prepared as described by
Cooper and Croxson (19).
The 95% confidence limits of the mean blank were: 0.003 - 0.005
mg/L. Based on this information, a sensitivity of 0.005 mg/L
could be achieved, a value very close to the 0.006 mg/L suggested by Thermo
Orion. This sensitivity however could be improved by
threefold, using 30 ml of urine for chromatography, but keeping the wash solvent
volume at 10 ml and elution solvent volume at 5 ml. Using 30
ml of urine, the sensitivity in measuring I in urine
samples by the ISE method was 0.0017 mg/L, comparable to the sensitivity of
ICP-M.S.
2)
Specificity
There are various ways of validating an assay in terms of its
specificity, one of which is by comparison with an accepted method.
Yabu et al (19) and Kono et al (20) validated the specificity of the
ISE method for direct measurement of urinary iodide levels by comparison with
the ceric ion-arsenious
acid
method (21).
However, their direct assay without prior purification proved unreliable
with urinary I levels below 1.27 mg/L. In our
U.S. population,
based on the latest nutritional survey, only 5% of urine samples evaluated, had I levels above 0.5 mg/L
(1). Therefore, the direct ISE method for urinary
I levels, although acceptable for mainland Japanese, would be worthless in our
population. By prior purification of the urine samples using
anion-exchange chromatography, we were able to achieve a
sensitivity 250 times better than that reported by the Japanese authors,
and 750 times better if 3 |