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the Myodil Action Group e-petition
Index
Page 2
This is a document showing the major points from the
comprehensive research report conducted by Dr. Susan Parisian about the
production, testing, and use of Pantopaque/Myodil. Some original
animal test result documents and other mateial she refers to can be found on
this website.
AMERICAN ANIMAL TESTS, RESULTS AND
ADVERSE REACTION REPORTS WHICH SHOULD HAVE STOPPED PANTOPAQUE (WHICH
BECAME MYODIL IN ENGLAND) BEING PRODUCED
1918, Dandy created radiographic visualisation of the
spinal cord by injecting air in to the spinal column.
1922, Iodinised Poppy Seed Oil (commercially available
since 1901) began to be used in doses less than 5cc's, but was recommended
that it be removed.
A 1932 statement of opinion by the American Medical
Association had discouraged the introduction of any foreign oily material
into the spinal cord.
1936, Eastman Kodak supply Ethyl Iodophenylundecylate as
the main ingredient of Pantopaque to Lafayette under trade mark.
1937 to 1938, Warren and Strain conducted animal studies
using Pantopaque which indicated that a inflammatory reaction with
production of Fibrosis was triggered.
1938, unlicensed Pantopaque was distributed as a
investigative drug to Physicians without proven safety data.
1941, T.B. Steinhousen's doctoral research of Iodinated
compounds showed that in his opinion Lipidol (iodinised Poppy seed oil
similar to Pantopaque) was unsafe to use in humans intrathesically.
After reviewing cat studies he found one died after injection, he also cited
earlier 1925 Rabbit studies that after intrathecal injection there was a 47%
mortality rate, and a 1938 study by Metier and Leake reported numerous
untoward reactions. Also 1941 study by Brown and Carr indicated
significant danger injecting iodinated Poppy seed oil in to the spinal
canal. His thesis included a study of the new compound Pantopaque, in
a series of tests using three dogs Pantopaque produced meningial irritation
symptoms ranging slight to severe. In another series using fifteen
dogs, 46% had slight meningial irritation, 20% moderate, and 7% severe, one
dog was unable to walk, and one dog died of gangrenous terminal ileum.
At termination of the study and autopsy, histological and gross meningial
changes were more severe than had been clinically suggested, including
granulamatis foreign body reactions, with acute inflammatory
polymorphonucleocytes (PMNs), phagolytes and fibroblasts with fibrous
adhesions involving the nerve roots, also clear cyst areas dispersed
throughout the spinal column, and scattered macrophages. Steinhousen
did the same test on nine dogs using iodinised Poppy seed oil, the results
were similar plus one dog died. Steinhousen's research in dogs
foreshadowed the acute and long term adverse events that came to be reported
in humans.
26/02/1942, Dr. Rigler, University of Minnesota, wrote
reporting his facilities unfavourable clinical experiences with Pantopaque,
indicating in his and his staff's opinion it did not improve imaging quality
and was extremely difficult to remove.
05/09/1942, Major R.G. Spurling wrote indicating
Pantopaque produced as many irritative symptoms as Lipidol.
In 1942 there appears to have been a conscious decision
to disregard clinical ethical conduct and intentionally ignore clinical
findings and fail to provide physicians with test results on animals and
humans but describe Pantopaque as safe using misleading statements.
04/11/1943, Lafayette, America, New Drug Application, Dr.
Walter Van Winkle FDA. requested from Dr. Strain animal safety data.
Dr. Strain stated he did not have very good figures on the acute
toxicity. In the 1960's the FDA also found that test results carried
out on mice (22/02/1943) were also inadequate to support Pantopaque safety.
1944, on the basis of safety for use the FDA were
hesitant to permit a NDA, the reasons being that reports gave the impression
large numbers of reactions of varying degrees of severity had been observed,
but that the entire product circular created the impression that reactions
were minor and infrequent.
24/02/1944, Major Robert Robertson, Chief of
Neurosurgery, Brook General Hospital, Fort Sam, Houston Texas, reported a
patient developed Adhesive Arachnoiditis.
14/04/1944, Despite unfavourable animal test results not
being supplied to the FDA, Pantopaque NDA was approved in the US, appearing
to have occurred without resolution of Dr. Van Winkle's FDA concerns
regarding product safety issues, but purely on "grandfather rights" based on
a few hundred favourable Military Hospital Myerlograms performed,
1946, Glaxo produce Myodil (Pantopaque) in the U.K.
21/12/1950, complaints on certain lots of Pantopaque
proved to be due to it containing 5% of Iodophenylundecanoic acid, rather
than 0.9%. A letter from Mr. Mees of Kodak's Distillation Products
Industries (suppliers of ethyliodophenylundecylate to Lafayette) sought to
create a legal distance from Lafaet's distribution of Pantopaque assuming no
responsibility.
03/12/1953, the American Journal of Roentgenology, Radium
Therapy and Nuclear Medicine indicated a usual injection of 6 or 9cc's of
Pantopaque, however the 1944 NDA recommended a dose of 2 to 5cc's.
Lafaet's labelling continued to make no reference to
potential serious acute or long term consequences associated with Pantopaque
(the expressed concern of FDA's Dr. Van Winkle), did not recommend doses of
2 to 5cc, nor emphasise the removal of all material, but did emphasise
injecting a larger dose than had been submitted for NDA.
1964, Mr. Hagan of FDA wrote of his concern regarding the
fever induced from Pantopaque injections which appeared to be related to the
Pyrogenisity of the product.
03/10/1966, FDA's James E. Wilson PhD. wrote Iophenylate
has been on the market for twenty years, but deaths have been attributed to
it's use.
Swartz, 1965, sights a 61 year old woman who died of
oblitaritive Arachnoiditis.
27/11/1967, Lafayette wanted to introduce a new drug,
Pantopaque ii. New tests were carried out on 24 pure bread Walker hounds by
Hazelton Laboratories, comparing Pantopaque i and ii. Results showed 5
dogs had clotted blood at the base of the brain and anterior spinal cord (1
dog Pantopaque i, 4 Pantopaque ii), 8 dogs had meninges visibly thickened (3
dogs Pantopaque i, 5 Pantopaque ii), in 6 dogs oily material was grossly
seen in the meninges (3 dogs Pantopaque i, 3 dogs Pantopaque ii). At
autopsy 2 Pantopaque i dogs had moderate to severe granulamatis reaction
surrounding large vacuoles in the space under the meninges and surrounding
some of the spinal nerves. There was moderate to severe Fibrosis
surrounding the spinal cord and scattered areas of granulamatis reaction
were present within the white matter of the spinal cord. The spinal
cord was surrounded by moderate amounts of old blood present under the
meninges. The following was the summary of Hazelton Laboratories: In
conclusion it can be stated that the intrathecal administration of
Pantopaque i and ii stimulates a Granulamatis Meningitis in the areas were
the compounds appear to localise. The majority of the inflammatory
reactions present in the animals on this study were of a sub-accute to
chronic nature. Pantopaque i stimulated granulamatis reaction in
primarily the lumbar region. Both Pantopaque i and Pantopaque ii
produced severe reaction in the cervical and thoracic cords.
14/04/1969, FDA recommended Lafayette delete the
statement: the small amount of material left in the sub-arachnoid space
usually is absorbed in two months (it actually remains for many
years). In the adverse reactions section to include severe
Arachnoiditis producing headache, fever, meningismous, pain in the back and
extremities and elevations in the white blood count and the protein count of
the cerebro spinal fluid and instances of lipoid granuleomas obstruction of
the ventricular system and venis intravation producing pulmonary
emboli. In contrainedations section Pantopaque is contrained in
patients with hypersensitivity to Iodine or its compounds. In
precautions section diagnostic tests of thyroid function involving Iodine
maybe invalid for many years, it is my understanding none of these
recommendations were followed..
25/06/1969, Lafayette withdrew NDA for Pantopaque ii,
from the memo and letter to FDA there appears to be no mention of the
adverse findings of the animal studies done by Hazelton Laboratories
relevant to the poor safety performance of Pantopaque I, the approved
product. Therefore the FDA were never informed of the animal toxicity
studies which showed Pantopaque i unsafe.
07/02/1972, Two hours after injection of Pantopaque two
patients at Holy Family Hospital, Atlanta, GA, developed Cerebral Adema,
Focal and Grandmal seizures, Hypotension, loss of bowl/bladder control and
Aspiration Pneumonia.
1977, Alcon purchased Lafayette.
18/09/1978, Medical World News Journal, reported on a Dr.
Henry L. Fefer article, "Arachnoiditis Risk after Pantopaque Myerlography,"
that of 400,000 yearly Myerlograms 25% will probably develop Arachnoiditis
and patients having two or more, 50%. Confirmed by animal studies, but
denied by Lafayette.
13/08/1979, Dr. Newton reported to a distributor of
Pantopaque an adverse reaction. Another physician/father reported
concern about his 25 year old daughter's condition being in a great deal of
pain, excitable and upset.
June 1982, a paper appeared in "Radiology" journal
regarding Pantopaque versus Amipaque used in monkeys which outlined
Pantopaque as a causative factor in Arachnoiditis.
July 1982, Johnston and Matheny studied 28 patients with
Arachnoiditis stating four of the patients had Myerlography after spinal
surgery and all four had severe Arachnoiditis.
25/04/1983, Eastman Kodak, supplier of Iophenylactulate
to Lafayette, became aware of legal activity surrounding Pantopaque and the
falling popularity compared to the new water-based Amipaque (Metrizamide).
1984, Lafayette released a caution against the use of
plastic syringes.
29/04/1985, Ms. Galene Tsipis of Drug and Poison
information control, Ohio, wrote a irate letter to Alcon Laboratories
(owners of Lafayette) about a adverse drug reaction (paralysis of the lower
extremities) involving a patient in a local hospital. She requested
clinical trial data and adverse reaction reports on Pantopaque, she was told
no information was available and she felt she was given the run-around.
June 1987, Alcon's drug experience complaint record
listed thirteen patient complaints of Arachnoiditis, Focal seizure, burning
in the lower back, Nausea, Allergic phenomenon and suspect Meningitis, and
two suites in Dade County, Florida. Label changes were made adding
severe Arachnoiditis has been reported.
1987, Alcon ceased production, but had stock with a shelf
life of five years.
15/03/1990, Scott Kerby reporter for Inside Edition rang
Mr. West (FDA) in connection with a patient who had three Myerlograms in the
early 1970's and was now severely paralysed with Arachnoiditis and had
attempted to sue Alcon Laboratories, but was told statute of limitations had
elapsed. Mr. West indicated in the 1970's the consumer/patient would
have been unaware of the risks, but the occurrence was well documented in
Radiological text books.
12/06/1990, Pantopaque was discussed on a T.V. consumer
show hosted by Geraldo Rivera.
26/09/1990, 25 plaintiffs launched a class action suite
against Alcon alleging permanent severe injuries, chronic pain, paraplegia,
quadriplegia and death from incurable Arachnoiditis.
30/08/1990, Wall St. Journal reported a suite of 300
plaintiffs.
1990, The Management of Pain magazine reported a noted
decrease in Arachnoiditis since the decrease in use of oil based Myerlograms
which was also recognised by the medical fraternity.
Conclusion: Physicians reported difficulty in removing
all the Pantopaque, not as described by the producers, Pantopaque primarily
remains unabsorbed in the body and is associated with chemical meningitis,
fever, shock, respiratory arrest, oblitirative Arachnoiditis, neurological
deficit, paralysis, focal and grandmal seizures, blindness, corda equina
syndrome, obstructive hydrocephalus, bowl and bladder dysfunction, syphilis,
sexual organ pain and dysfunction, trauma, numbness, paraplegia, loss of
sensory and motor function, pain in lower trunk abdomen and legs, coma and
death, intractable burning pain worsened by physical activity which stretch
the lumbar nerve roots and not ameliorated by narcotics. Resulting in
a lifetime of severe unremitting pain.
After 40 years doses were increased from 5cc's to 30cc's
(the original NDA 2 to 5cc) increasing patient risk.