‘Read not to contradict and confute, nor to believe and take for granted,
nor to find talk and discourse, but to weigh and consider’.
‘PAIN MAKING IN AMERICA’
‘THE ONGOING ADDITION OF DOCTORS’.
Today tens of millions of people throughout America and Australia and within another 105 Countries are suffering from horrendous pain and disability without any knowledge of its cause or been misled. My Blog is to share with you ‘at last’ the truth. If you have had an injection of an x-ray dye into your spine in the past, and instead of getting better over time you have been slowly got worse and worse, here’s why. The x-ray dye was called Iophendylate Pantopaque and it is now officially recognised to have been far too toxic for human use, and should never been approved by the FDA. In fact it has been estimated that over the life of this too toxic dye [until 1996] on average 400,000 Americans per year have been injected, ‘you do the maths’ “you are not alone” in Australia it runs in the hundreds of thousand and worldwide around 300 million if the other 19 brands used are added into the mix, its just each of you are not being told the cause of your horrendous pain and disability. And you wonder why you are so much pain and cant get out of bed, check this out, look what Iophendylate [the active ingredient] of Pantopaque and the other 18 brands does to a polystyrene cup in 6 hours, and they put it in YOUR back!!!
Today it now can be told that this too toxic x-ray dye ‘chemical make-up’ was a by-product of waste water from Kodak film processing and consisted of Hydrochloric Acid, Sulphuric Acid, Benzene, (now the number one carcinogenic in the world today) and Potassium Permanganate to name just a few, not forgetting the 30.6% of Iodine, don’t believe me, look it up, the evidence lies gathering dust in the Dyson Perrin Library at Oxford University in England, or in your Biomedical Library at your University.
Meet Bonnie, a fellow survivor of being injected with this too toxic substance, there are 3 million + ‘Bonnie’s’ [female but also male] in this country.
Why is this NOT on every media channel and front pages of Newspapers everywhere, I have posted this 3 years ago and no media outlet here in Australia or overseas have picked this up what we need to ask is WHY? Why are they NOT coving this abuse of American and Australian lives especially now the opiate issue in America is a hot topic. Maybe one of them will have a second thought, and look at the documented evidence that supports ALL this. Maybe FRONTLINE may want this story, do YOU reading this know someone at FRONTLINE?
Well as you can see by this next video clip it was covered by a FOX Senior Correspondent Geraldo Rivera 27 years ago, but again it died a quick death, and what is very clear today, is, ‘NO ONE‘ listened.
That youtube video was produced in the 90’s when ‘this issue’ was whilst serious with the belief that around 100,000 Americans had been injected, today that figure stands at approx 20 million, evidence today show on average 400,000 patients per year were exposed to this too toxic substance through injection. [Used in America between 1936 and 1996]
Whilst this Blog is about those injured by this too toxic “dye” in America mainly, if you wish to know about what is happening in Australia, go to https;//pantopaquemyodil.wordpress.com. I want to share the following, prior to giving you a ‘step by step’ how this happened in these countries and why. As I have said previously whilst this “dye” was developed and manufactured in America it was also copied by Glaxo and together it was sold around the world in 107 countries, and for more than 40 years it was the ONLY substance used as a “dye” worldwide. Copies of my Myodil Blog now finished has been provided to others ‘overseas’ for safe keeping, ‘just in case I end up in the sand hills’ I will release at a time suitable to the full exposure of what happened. So those oversees holding copies of all my research have been instructed to forward their copy to the media/authorites if such happens.
If I may, just for a moment mention my Country Australia where this was sold and hundreds of thousands were injured like bonnie, many also became wheelchair bound or bed-ridden and sadly for thousands, ‘death’ including my mother. For those reading this that were abused this way in Australia, as I mentioned earlier go to http://pantopaquemyodil.wordpress.com for a detailed Australian Blog of how it happened here, under the disguise of ‘HUMAN EXPERIMENTATION’ without Approval of a General Marketing License. This lack of Australian Regulatory Approval didn’t stop the American developer/Manufacturer selling it to the Australian Distributor [Dr Ernie Hughes still alive as of 2016 lives in Melbourne] to sell throughout Australia, and like the FDA the Australian Regulatory Authority the TGB [now known as the TGA] were asleep at the wheel.
This also happened in the other 105 countries including your neighbours being Canada here is a video I did for the Canadian sufferers in 2009, please note this is NOT the same video as the one above showing Bonnie, She is the face, or should I say body of all that have been abused this way. Just click on it, it runs for 8 and half minutes. What I draw to your attention that the contents whilst all is very important viewing please see the end section where the British Govt support my contention that this abuse for nothing else but ‘money’ and such needs to be publicly exposed and those involved ‘held accountable’ , anyway here is the Canadian video.
THIS IS A DIFFERENT VIDEO THAN THE ONE ABOVE, THIS RUNS FOR 9 MINUTES.
Back to the American Blog.
Whilst I will provide you here in this Blog all the historical documented evidence of Pantopaque from the beginning in 1936 up to 1996 when ALCON surrenders Pantopaque’s General Marketing License back to the FDA, and what happened over that period. It would be amiss of me not to provide the hidden adverse reaction reports that were never submitted to the FDA as well as close to 280 submitted adverse reaction reports to the FDA by ALCON the last year Pantopaque was used. I will also provide here a copy of evidence of the multi-million dollar FDA Fine handed down to ALCON because the Company NEVER reported all the deaths of patients injected with Pantopaque to the FDA as required.
However before I provide you 60 years of the damning evidence of how this happened ‘step by step‘, I have decided to also provide you with ALL the evidence NEVER SEEN BEFORE of a multi-million dollar Settlement that took place some years ago, in fact, 21 years ago, hidden away, out of sight, until now, a out of court settlement that ran into tens of millions of US Dollars for one Pantopaque American patient alone. This now obtained evidence used against ALCON and LAFAYETTE PHARMACAL was so damning they had no choice but to settle, and today you too have that evidence, ‘use it wisely‘.
So here it is.
Here first is a picture below of the man who made this too toxic radiographic x-ray dye, his name was Arthur Kunz of Lafayette Pharmacal, what is so horrendous is that he knew it would cause you this pain and disability and led you today to have Chemically Induced Adhesive Arachnoiditis, that’s if you are told, that is, 98% of sufferers are never told, “it’s all in your head“ is the common remark.
You may wish to watch a video deposition taken from that Court action I mentioned given by Arthur Kunz it goes for more than 6 hours, I have split it into two separate sections, with this video I will also place all Exhibits relied on. I will also provide the related written transcripts of verbal Depositions given by two other Lafayette Pharmacal/Alcon Staff members being Sharpe [Production & Quality Control Manager] and Newton [Marketing & Sales Manager]. Based on the video evidence given here by Kunz, [General Manager] and Sharp [Production & Quality Control Manager] and Newton [Marketing & Sales Manager] verbal evidence on behalf of Alcon and Lafayette, plus all the Plantiffs Exhibits submitted copies shown below. Due to such damning evidence Alcon and Lafayette Pharmacal had no choice but to ‘Settle out of Court’ for the largest settlement to date regarding Pantopaque that ran into the millions and has been said to have been around 60 Million Dollars, although this has never been substantiated due the Court records being sealed, but have been given this information from a very reliable source. I will also post another Sharp verbal Deposition [unable to access the video’s yet] done 8 years later in the Palmer case, this will also include the 36 Exhibits relied on by the Plaintiff.
Here is Kunz 6 hour video, may I suggest you have a pen and note pad at hand for I am sure you will want to write much down, of what is disclosed.
ESPECIALLY WHERE HE STATES UNDER OATH THAT THE COMPANY KNEW IT WOULD CAUSE [CHEMICALLY INDUCED] ADHESIVE ARACHNOIDITIS IN 1945 LESS THAT A YEAR AFTER THE FDA HAD LICENSED IT.
WORST STILL, THE DEVELOPERS EASTMAN KODAK – ROCHESTER UNIVERSITY AND HAZELTON LAB’S KNEW YEARS ‘BEFORE’ THE FDA LICENSED IT, THEY JUST DIDN’T TELL THEM.
***GUESS WHO ‘TODAY’ HOLDS ‘PATENTS OR RIGHTS’ON MUCH NEEDED DRUGS ***
FOR THOSE EXPOSED.
YEP YOU GOT IT, THOSE THAT DEVELOPED/MANUFACTURED IT.
HERE’S THE FIRST HALF OF THE VIDEO
AND NOW THE SECOND HALF
E X H I B I T I N D E X DOCUMENTS NOW AVAILABLE
USED IN THE KUNZ VIDEO DEPOSITION
Here is a copy of the first page of the first of two Sharp Depositions which is 362 pages long, below it is the full transcript as a PDF file. Next will be the Barry Newton Deposition which is 303 pages plus graphics. A second Sharp Deposition that was done 8 years later can be found further below.
ALL E X H I B I TS AVAILABLE ON REQUEST.
Here is the first 4 pages of the Barry Newton Deposition also taken from the Walsh case that ended up being settled out of Court its 303 pages and poster graphics. When you read both Depositions [Sharp/Newton] and watch the 6 hour Kunz video Deposition [above] you can see why they settled.
Ok time to put the jug on.
NEWTON DEPOSITION FRONT PAGE
FULL DEPOSITION AS A PDF LINK TOTALING 303 PAGES AVAILABE ON REQUEST.
15 RELATED POSTER EXHIBITS
ALL 15 EXHIBIT POSTERS USED AS A PDF
ALL E X H I B I TS AVAILABLE ON REQUEST.
Here is a copy of the second Sharp verbal Deposition 8 years after the Walsh case, sorry currently no video but I am hoping to receive copies soon. I will like the earlier Sharp Deposition place not only the first page as I did before but this time the first three pages, followed by the full verbal Deposition as a PDF file followed by the 36 Plaintiffs Exhibits he relied on. My purpose in posting them all is through the information gleaned, you will be able to be better informed as well as those considering taking legal action accessing pertinent facts/evidence unseen until now which can and will strength your case.
AGAIN, ALL E X H I B I TS USED IN THE SECOND SHARP VERBAL DEPOSITION AVAILABLE ON REQUEST.
Or those that wish to full understand how this was allowed to happen, please read on.
Just before we start this mammoth task [1936 – 1996] I believe you will find the following interesting. In June 1998 the American National Institute of Health listed 80 secondary related medical conditions and/or symptoms as a ’cause or effect’ to exposure [injection] of Iophendylate. [Pantopaque] which means also Myodil and the other 21 Brands sold throughout the world, being the “same” product. I will now list these 80 secondary related medical conditions and/or symptoms below, however, please remember these were listed in 1998, seventeen years ago I have not yet brought this list up to-date, however, explains a lot of that which you are suffering from today.
I need to place this here, NOT all these secondary related conditions /symptoms listed here will you develop, the development are individually based, based on a range of variables which I will not go into here but this list is just that, a list of medical conditions/symptoms that people have developed since being injected, ‘It doesn’t mean YOU will develop it/them’, ok.
This list is as was written by the FDA’s Spontaneous Reporting System of the Division of Epidemiology and Surveillance on the 12th June 1998.
To get the full name, just enter it into Google to find.
ALLERG REACT. AMNESIA. AMBLYOPIA. ANOREXIA. ANXIETY. ARACHNOIDITIS. ASTHENIA. ATAXIA. ATROPHY MUSCLE. BRAIN SYND CROM. CARDIOVASC DIS. CNS DEPRESS. CONSTIP. CONVULS. CRAMPS IN LEGS. DELIRIUM. DEPRESSION. DIZZINESS. DYSPHEA. EDEMA PERIPH. EMOTION LABIL. ENCEPHALOPATHY. FEVER. GAIT ABNORM. GI DIS. HALLUCIN. HEAD PAIN. HEART ARREST. HEM. HEMATURIA. HYPERTONIA. INCONTIN FECAL. INCONTIN URIN. INJECT SITE REACTION. INSOMNIA. INTEST PER. JOINT DIS. MALAISE. MIGRAINE. MYALGIA. MYASTHENIA. MYOPATHY. NAUSEA. NEOPL CHS. NERVOUSNESS. NEURALGIA. NEURITIS. NEUROPATHY. PAIN. PAIN BACK. PAIN CHEST. PAIN INJECTION SITE. PAIN KIDNEY. PAIN NECK. PARALYSIS. PARALYSIS SPASTIC. PARAPLEGIA. PARESTHESIA. POLYNEURITIS. RASH. REFLEXES DEC. RHINITIS. SCLEROSIS MULTI. [Interesting eh] SEX FUNC ABNORM. SHOCK. SKIN DISCOLOUR. SPEECH DIS. SWEATS. THINKING ABNORM. TINNITUS. TWICHES. URIN RETENT. URIN TRACT DIS. URIN URGENCY. VISION ABNORM. VOMIT.
Furthermore in America between 1991 and 1995 a total of 335 adverse reactions were reported after patients were injected with the chemical x-ray dye known as Iophendylate (Pantopaque) of these, 275 developed [Chemically Induced] Adhesive Arachnoiditis. This is a 82.3% ratio NOT the ‘less than 1%’ that has been used always in the past to state it was ‘RARE’. In fact, this less than ‘1%’ was taken from the use of Lipiodol NOT Iophendylate Pantopaque.
However, until now this fact has never been challenged, consider yourself challenged Eastman Kodak, Glaxo, Lafayette Pharmacal, Alcon.
But before we commence on our Journey by way of this Blog into the horrendous abuse of human life I need to speak to those that have arrived here that have been abused through Epidural Steroid Injection/s, today sadly ESI has become the largest ‘known’ cause of Chemically Induced Adhesive Arachnoiditis, this Blog however, is about the previous abuse of human life, prior to ESI, Iophendylate Pantopaque in America. So for those that believe that Epidural Steroid Injections [ESI] maybe the cause of their suffering I direct you to the following link http://www.burtonreport.com/infspine/epiduralsteroidshistory.htm just released by my great friend Dr Charles Burton. Please also go to the following youtube website link End Depo Now Campaign as well as the following PDF link to continue your journey of discovery seen here in blue. ESI History.
Furthermore, if you wish to have a visual understanding follow this youtube link.
What is not mentioned here is that NONE of these procedures have never ever been approved or sanctioned by the FDA.
So, lets move on, on our Journey of discovery regarding this too toxic x-ray dye Pantopaque.
First let me say that the link between the dye and your condition ‘chemically induced adhesive arachnoiditis’ is known, it’s just that the Medical Profession and your Government are not telling you, this old FDA approved x-ray dye known as Iophendylate or more commonly known as Pantopaque was far too toxic for human use and has damaged your spinal nerves and related organs leading to your current condition.
This blog will explain not only when this first started in America but will also provided the historical documentation to support all that I share, furthermore, it will list all those involved, some are now dead others though are very much alive. As you read this you will become very angry just like I, but whilst you will wish to seek legal action you will need to understand the complex nature of doing so, for I know, I’ve tried. All I ask in return for providing all this information to you, is this, you must share this blog to as many other sufferers you can including anyone that you know ‘in the media’ so the full extent of this abuse can become better known, will you do this for me?
Lets begin, it all started in 1936.
This substance known as Pantopaque whilst its called an x-ray dye was nothing more than ‘waste water’ from Eastman Kodak film processing, with added iodine.
The most difficult part in writing a blog such as this, is in ‘what does one share, and in what order‘ for like me in the past, I am sure you have a specific area, or areas you want to investigate.
So how do I share such a complex story that covers 60 years?
Here is an interesting but sad fact, The American President John F. Kennedy was also injected with Pantopaque, here’s what he was often heard muttering.
“God What a Beating I’m Taking”
Your pain and disability like JFK is due to the too toxic nature of this substance, whilst I made reference to this above, I decided to place it here once again because its inconceivable that anyone would really believe that such a chemical mix would do no harm to humans when the basis of the chemical mix consisted of the following…Hydrochloric Acid, Sulphuric Acid, Benzene, (now the number one carcinogenic in the world today) and Potassium Permanganate to name just a few, not forgetting the 30% of Iodine. However, this did not stop them they went ahead and manufactured it after lying to the FDA to obtain the General Marketing License.
OK, LETS START AT THE BEGINNING
WELL THE BEGINNING OF IOPHENDYLATE PANTOPAQUE THAT IS.
FOR THOSE INTERESTED IN LIPIODOL, PLEASE SEE LINKS LATER INTO THIS BLOG.
‘IOPHENDYLATE MYODIL BLOG TO BE RELEASED SOON’.
In 1940 as part of a Ph.D degree at the University of Rochester John T. Plati [see below] synthesised a range of liquid contrast mediums which were all ethyl esters of iodinated aryl acids and were …’designed to be absorbed at the site of injection, as well as to provide adequate contrast for radiographic diagnoses’… .
Whilst Plait’s Thesis was awarded to him in 1940, the synthesising of these liquid contrasts mediums began in the mid 30’s and from one of those mediums named ethyl iophendyl-undecylate’ became Pantopaque before commencing on its journey into unknown. Whilst below is a copy of the front page of that thesis, a full copy of this Thesis is provided to you below that.
Here below is a full copy of Plati’s Thesis.
Please note who Plati acknowledges especially the Funder of his research, that being
As you can see Plati lists 68 Experimental Pyelographic compounds, pyelography means an …’intravenous pyelogram or IVP for short is a radiological procedure used to visualize abnormalities of the urinary system, including the kidneys, ureters, and bladder’… . The other Experimental compounds of Plati consisted of 48 Experimental Liquid Contrast mediums [see initially page 44 then go to page 45] where you will see the following highly important statement …’conclusive evidence of the nature of the mix [being Ethyl Iodophenylundecylate] was NOT obtained’… . Taken further from Plati’s Thesis regarding Ethyl Iodophenylundecylate is the follow two statements first on Page 4 …’When Ethyl 4-iodophenyundecylate and Ethyl-iodophenylstearate were injected into the spinal cannel, both were tolerated but unfortunately neither disappeared completely from the site of the injection during a period of 3 months. Accordingly it was decided to investigate the effects of decreased chain length’… . Now go to Plati’s Thesis once again this time toPage 59 where it states …’Ethyl 4 Iodophenylundecylate shows a lethal dose of 6g per kg and therefore much safer than valerate. Unfortunately, it is not absorbed with the rapidity that is considered essential from brain and spinal work’… .
[MY WORDS: ‘ what is NOT reported is ALL the rabbits they tested it on ‘DIED’, and 25% of dogs.]
‘They then stated that this slow absorption may be a handicap in general use.’
Here is a copy [see below] of ’Ethyl 4-iodophenylundecylate make up and mix is shared with the reader, [See Page 198 and Page 190] Please note for this is critically important, whilst this change took place prior to its FDA NDA, [for gaining general marketing approval] it was then changed again afterwards, in fact in all 5 times, the first in 1951 and 4 more times through the its life as a contrast medium, I’m not a Pharmacist or an expert in Chemistry but surly this causes an imbalance in its use, and ‘safety to the patient’?
Feedback by anyone reading that is would be appreciated.
Plati also refers to a second compound that …’maybe suitable’… this being ethyl 4-iodophenylvalerate here are those details, I have placed this here because soon you will see that together John Plati, William Strain of Eastman Kodak and Stafford L Warren of Rochester university and the Manhatten Project [yep you read it right] so please remember that name Stafford L Warren, for he plays an intricate role in ALL this. For the three of them together published two related Medical Journal Articles in the Journal of American Chemistry Society, copies of that posted a little later on. This second compound of Plati named ethyl 4-iodophenylvalerate is in Plati’s view similar to Ethyl 4-iodophenylundecylate.
You be the judge.
Below was taken from Plati’s Thesis Pages 3 and 4 regarding ethyl 4-iodophenylvalerate the last paragraph is an interesting read.
THE FIRST DOCUMENTED EVIDENCE OF THE COMMENCEMENT OF PANTOPAQUE FROM DEVELOPMENT BY ROCHESTER UNIVERSITY TO THE FDA.
On the 9th of September 1941 a Dr Strain of the University of Rochester School of Medicine and Dentistry in N.Y. calls on Dr Walton Van Winkle, Jr. and Dr W. F. Kennedy of the FDA to discuss a new contrast medium for radiography of body cavities which was being developed. [below is a Memorandum of that visit] Dr Strain informs them that this proposed preparation has been named Pantopaque, he informs them that the drug is to be used in the spinal canal, nasal sinuses, the common duct, and the fallopian tubes. [I will speak about these ‘other areas later’, but will say this, the promotion of such areas using Iophendylate Pantopaque and how such was allowed to enter the market place is of great concern to me and others, and will require further investigation, but I will continue with the FDA memorandum] Dr Strain informs them that this chemical has been under study for the past two years [and] that their pharmacological studies on dogs and other animals also have been in progress for the same length of time., and that 15 intrathacal injections have been made. [What Strain is NOT telling the FDA is this, whilst he is portraying that this is a new radiological medium being tested on Dogs and other animals he forgets to inform them one of these animals are human beings being tested in ‘other’ University Hospitals. ‘See University of California Letter’ posted further below dated December 1941] Strain also got Dr Spurling of Walter Reed Hospital to test it on 6 unsuspecting military personnel prior to getting official authority from the Army to use it, this official permission did NOT take place until a full year later, see copy of such again further into this Blog. Strain continues to mislead the FDA regarding Clinical Human Trials by saying he’d hope to have at least 100 intrathecal injections of the material prior to submitting a new drug application, he then asks Dr Winkle and Dr Kennedy of the FDA for a comment on their opinion concerning the adequacy of that number. To which was pointed out to Dr Strain that the FDA [‘the administration’] could not undertake to specify any given number of cases which might be considered adequate in order to demonstrate the safety of the preparation. So Strain, supplied thousands of ampoules to end-users not only at Military Hospitals BUT Civilian Hospitals as well, all without FDA approval and systematically culled all those that had less favourable responses and as you will see later submits ‘only’ those that sent favourable results as supportive evidence when applying for a NDA. [New Drug Application on the 23rd of July 1943] Remember, patients are never seen by end-users after completion of the myelogram, so other than maybe a couple of ward visits over the following couple of days no adverse reaction is seen, or reported, due to the current patients spinal injury etc to the end-user, being the Neurosurgeon in most cases at this moment in time did the myelogram.
Here the copy of that Memoramdum.
On the 13th September 1941 Dr Stain once again visited the FDA to ‘it seems’ get some advise whilst dropping off a copy of their proposed Product Label for Pantopaque. What is very interesting is what he stated regarding unable to obtain data of the toxicity issue of Pantopaque, see below. I had to rewrite it due to the poor quality but will hope to have good copies soon.
I have rewritten the above so you can understand what has been recorded, its below in italics.
Doctor Strain then asked for comment from us concerning the quality and toxicity of the pharmacological and clinical evidence which he had recited. He was told that we should like to have a complete details of the fatal dose of the preparation not only when given intrathecally but also when given parenteral and by mouth, since, when used for delineation of the nasal sinuses, most of the material will be swallowed and therefore the toxicity when taken orally is important. Likewise, we told him that his results seemed to indicate that the material was slowly absorbed from the spinal canal and hence the chronic toxicity of small repeated administration of this material would, of course, have a bearing on the problem of toxicity; that we would also desire to know the degree of irritation produced by this substance as compared with other agents such as Lipiodol used under similar conditions, this information to be obtained using the material in every site in which it is proposed to use it. We suggested that a simple comparison of its ability to produce irritation, as compared with like substances, could be made by using a frog muscle nerve preparation and supplying this material in various concentrations in spinal fluid to the exposed nerve and noting the amount required and the time of onset for muscular twitching to occur. Comparisons could be made with plan spinal fluid and with spinal fluid containing Lipiodol. This would afford a reasonably qualitative and semi-quantitative measure of the irritant action of this material upon nervous tissue. Dr Strain mentioned that they had been doing some studies or irritation with this material using the rabbit’s eye as a test subject. Additional pharmacological evidence, including the rate of absorption, from intramuscular injection, intrathecal injection, and oral administration, together with complete histological studies of the animals needed — particularly those showing any reactions to the material — should be submitted. What Strain is NOT telling the FDA is that this unproven yet to be safe medium is being tested on Humans in clinical trials. [Sounds an awful lot like what they did in Australia in the early 70s without the Australian Government being aware, it seems these people are ‘a law to themselves’]
It was explained to Dr Strain that the comments offered were not of course, intended to indicate the exact information required prior to submitting a new drug application, but that this information should be submitted among other things.
The proposed label to be used in distributing this preparation to various investigators was then submitted, reading as follows:
6 ampoules – 10 cc Size – Sterile
Pantopaque Contrast Medium for
Radiolography of Cavities – Do Not Expose to Sunlight
‘Caution: New Drug – Limited by Federal Law to Investigational Use’
Prepared and Distributed by the Department of Radiology, School of Medicine and Dentistry, University or Rochester, Rochester, N.Y. Each Ampoule Contains Sufficient For the Withdrawal and Administration of 10 cc.
NOT FOR INTRAVENOUS USE
Page three Original
As before I have rewritten the above so you can understand what has been recorded, its below in italics.
Page three. [Retyped]
No adverse comment’s was offered on this label and it was not left with us.
De Strain stated that he would forward specimens of the labelling and a resume of the work accomplished to date. He stated that this material would not be intended as a new drug application but would be merely for our information, and requested that we feel free to make any comments which we believe necessary.
Walton Van Winkle, Jr., M.D.
H. F. Kennedy, M.D.
Cc ED Es
Cc Drug Div
HFK – WVW
Cast you eyes to the date above, its 13th of September 1941 and Dr Strain is sharing with the FDA problems they were having regarding the toxicity of Pantopaque when testing Pantopaque on a selection of animals, and they the FDA requests specific data on such. But what you will see below is these same animal tests using Pantopaque of which they will be relying on for their NDA application, is part of Steinhausens Thesis presented 3 months earlier for his doctorate. It seems that the FDA is being once again mislead, whilst they are trying to ensure Pantopaque is safe for use on humans by requesting specific data the developers are already trialling it on humans at military and civilian Hospitals.
In June 1941 a Theodore B. Steinhausen at the age of 66 submitted [in part] his thesis [see below] to fulfil the requirements for the degree of Doctor of medicine with honour in the School of Medicine and Dentistry at the University of Rochester. This study which was funded for the Radiopaque Group by Eastman Kodak Company consisted of carrying out multi animal studies on one of Plati’s compounds being ethyl-iodophenylundeclate which Plati reported to be and I Quote: …”the best of them”… .
This Thesis was titled:
AN EXPERIMENTAL STUDY ON IODINATED COMPOUNDS
FOR INTRATHECAL USE
and was the ‘beginning’ of the devastation throughout the world today, of ‘ethyl iophendyl-undecylate Adhesive Arachnoiditis’.
Below is the front cover of Steinhausen Thesis, and below that his full Thesis.
Steinhausen’s research in animals [dogs] mirrored the significant acute and long-term adverse events found later in human patients following the intrathecal injection of Pantopaque for myelography. The question that needs to be asked, is this, based on Steinhausen’s research, and his findings why did he come up with the following four conclusions: 1. Of the 26 ethyl esters of various iodinated organic acids, only ethyl iodophenylundecylate seemed suitable for myelography. 2. Ethyl iodophenylundecylate appeared to be absorbed and as long as any of the ester was present there was some pathological reaction about the compound. 3. Comparative tests with the standard iodized poppy seed oil showed a definite but different pathological response which persisted indefinitely, since the compound was very slowly absorbed. 4. Ethyl-w-(4-iodophenyl)-o-valerate, although not suitable for myelography, had found clinical application as a contrast medium, at the end of his Thesis?
I will paste a copy of all these animal studies results that he refers to in his Thesis further below.
Now as I mentioned a few moments ago Plati Strain and Warren penned two medical journal articles in relationship to both of these two compounds. The first is titled: Iodinated Organic Compounds as Contrast Media for Radiographic Diagnoses. I. Iodinated Aracyl Esters. It was received by the Publishers on the 21st of November of the same year, in fact 20 weeks after Plati presented his Thesis for evaluation to the University of Rochester. To date I am awaiting the specific date of his Doctorate Award.
Here is a copy of the front page of the first Medical Journal Article.
Below is a full copy of this Medical Journal Article.
Please see in the above MJA the section titled ‘Physiological Applications’ which can be found on the second page left column last paragraph which also carry’s over to the right column. Were it states …‘The compounds were tested as prepared by intrathecal injection in dogs, since the spinal canal represents the most sensitive site which they might ultimately be used. Of the group, the mixture of isomeric ethyl iodophenylundecylate… [my words, please note they have dropped the 4 chains] …gave very satisfactory results in the animals tested’… .
Now let me take you to that study in detail to see if such …’gave very satisfactory results as stated’… .
LINK ………Intrathecal Injection of Pantopaque in Dogs………
As you can see it states …’ of the 55 dogs injected with pantopaque, 3 died’…, here in America on average 400,000 patients were injected with ethyl iodophenylundecylate Pantopaque each year for 60 years, I will let you do the maths. But when I went to school that equates to 21,818 recurring.
Here is a copy of the second Medical Journal Article, first the front page, then the full copy.
Here below is the full Article.
Please see below a list of the Pantopaque Animal Tests [1936 – 1944] prior to Eastman Kodak INITIAL application for a General Marketing License in early 1944.
As you can see, each has a link to a PDF file showing the specific test data and most importantly the result/findings.
Also please note in this article/test below refers to the dose and refers to the dose in Humans if one as I did calculate that, it arrives at 2.85cc.
This 2.85cc became the recommended dose for human that’s why they not only produced 3.00 cc ampoules but supplied such to the US Military Hospitals to try, prior to their FDA License application.
‘The follow piece which I share here explains the cause of CIAA by Pantopaque around the world. When Eastman Kodak and Partner applied for the Iophendylate Pantopaque License they CHANGED the previous recommended dose [given to these Hospitals] FROM 3.00cc to 3-5cc [from a dot to a dash] by increasing the recommended dose this way they changed the dynamics of CSF toxicity using Pantopaque which in turn started off the development of CIAA’ worldwide. ©
‘The severity of CIAA is caused mainly by the level of the dose of this very toxic chemical above 2.85cc used as well as multiple build-up through multiple Myelograms that is most popular in America as they aspirated 70% to 90% after the procedure was completed’. ©
This clearly explains the 2 causes of CIAA using Iophendylate [Pantopaque/Myodil and the like] one of a build-up [Pantopaque] the other non-removal [Myodil] and the other 20 brands of the same sold around the world. ©
Pantopaque Animal Tests [1936 – 1944]
Intrathecal dog experiments comparing iodised poppy seed oil, Ethyl-w(4-iodophenyl)-n-valerate and Ethyl-iodopheny-lundecylate [Pantopaque]
LINK ………Intrathecal Injection of Pantopaque in Dogs………
Using Ethyl-iodophenylundecylate. Findings. Chronic Toxicity following inraperitineal injections of liquid contrast media in Rats.
Intrauterine Injections of liquid contrast media in Rabbits using Ethyl-iodophenylundecylate.
Chronic toxicity of liquid contrast media by intrapleural injections using Ethyl-iodophenylundecylate in Rabbits and one dog.
Using Ethyl-iodophenylundecylate. Findings. Acute Toxicity of Ethyl-iodophenylundecylate (Pantopaque) by oral Administration to rats including Table 1.
LINK ………….Oral Admin to Rats 1936……………
If you have difficulty reading ANY of the links just click on each page and it will change to blue and become easier to read.
Acute Toxicity of Ethyl-iodophenylundecylate by intravenous injection in Dogs and Rabbits.
LINK ……….Intravenous Injection in Dogs and Rabbits………..
Physiological Assay of Ethyl-iodophenylundecylate by Intrathecal injection.
Absorption of Ethyl-iodophenylundecylate (Pantopaque) from the Subarachnoid Space.
Its important to read the related medical Journal articles published as a package in December 1946 regarding these 1936 – 1941 animal tests which I will post later, otherwise I will be jumping too much around. What I ask you to note is the outcome of the animal tests [see above] and what is reported in these Medical Journal Articles years later especially the dye used referred to in the article, and what was FDA licensed. I will explain more later, but licensing for instance Iophendylate [Pantopaque] for intrauterine injection when serious reactions when used on Rabbits were found, however, see what is reported in the article. It seems to me, the FDA was not checking this, oh, that’s right Lafayette Pharmacal never submitted the true findings to them.
Ok, lets move on.
When one reads the Steinhausen Thesis and then the article he published in tandem with Dr William Strain from Eastman Kodak and Dr Stafford Warren from Rochester University [who was soon to become the Medical Radiological Advisor for the Manhattan Project] you find massive inconsistences as you can see below.
‘THE DIFFERENCES BETWEEN STEINHAUSEN 1941 THESIS
AND HIS PUBLISHED MEDICAL JOURNAL ARTICLE OF 1944′.
This paper will share with the reader the findings of Theodore B. Steinhausen, which he recorded in his Thesis, and the differences between this and his (jointly) published medical article that was submitted for publication in Radiology June 1944. [see below] Titled: Iodinated Organic Compounds as Contrast Media for Radiographic Diagnoses.
Here is the front page of that article, below is a PDF of the full article.
Here is the full copy below as a PDF file see III MJA
Both of these studies were aided by a grant from the Research Laboratories of the Eastman Kodak Company.
Further into this Blog I again post the above article III MJA but for a different reason, but just as important.
In this Thesis, Theodore B. Steinhausen acknowledges Dr Joseph B. Furst who he states carried out much of the preliminary work reported, he also acknowledges Dr Clarence Dungan whom not only completed these preliminary studies but with Theodore B. Steinhausen performed the early experiments with ‘ethyl iophendyl-undecylate’. Even in the ‘Introduction’ of Theodore B. Steinhausen thesis he refers to the fact that ethyl-iodophenylundeclate although at investigation was deemed satisfactory for clinical use in myelogrphy, it was only being used in a …‘limited way’….
If the reader wishes to gain a insight into as to ‘why’ an iodinated oil contrast medium [dye] had been developed you need to return to 1919, and Dandy’s introduction of air as a suitable contrast medium to outline the subarachnoid space.
Here below is the front page followed by the full copy as a PDF.
Here is the full copy of Dandy’s 1919 MJA regarding the use of Air in Myelography,
To follow the move from Air to oil based contrast medium [dye] you need to follow this link at http://pantopaquemyodil.wordpress.com once you have opened it go to the right side of the page and you will see a bunch of links, click on the one that starts with the following, …’Glaxo and Eastman Kodak hidden 1940s Iophendylate correspondence’… and once it opens you can read more on the life and death of this oil base contrast medium, known as Lipiodol. However, to set the scene as to why they stopped using Lipiodol I wish to place two related MJA’s here, I will place the front page of each here and then below each a copy of the full MJA as a PDF file. The first was written in 1939 Titled: The Effect of Iodized Oil on the Meninges of the Spinal Cord and Brain this MJA was published in Radiology and was penned by L. H. Garland MD and a very important fact, it was read before the 25th Annual Meeting of the Radiological Society of North America at Atlanta December 11 – 15th 1939.
Here below is a full copy as a PDF
The second MJA I wish to share with you is Titled: Irritating Effect of Iodized Vegetable Oils on the Brain and Spinal Cord when Divided into Small Particles. This MJA was penned in 1950 by Rudolph Jaeger and can be found in the Archives of Neurology and Psychiatry.
Here is a full copy below as a PDF
Please note the following for it ‘once again‘ shows the toxic nature of injected Iophendylate [Pantopaque] this can be found in the MJA above.
Furthermore, please see third last paragraph [last page] of this specific MJA and remember this was written in 1950, where the author states the following …’Extensive adhesion’s are no longer found when Ethyl-iodphenylundecylate, now in common use, is completely removed prior to operation’… . For all those that never had any of it removed like I and all those in the UK and around the world ‘this MJA can be used as a basis of a legal argument against Glaxo’. But as you know, the British and Australian Government has put a ‘STOP’ to such legal action using the public purse, and the Private Sector are too scared.
I have also listed a selection of some of the related Medical Journals you maybe interested in. If you just need a short overview it all started in 1921 when the first ever oil base positive ionic contrast medium [dye] was developed, it was known as Lipiodol as you will see there, Lipiodol was soon found to cause [Chemically Induced] Adhesive Arachnoiditis [CIAA] so the Radiological world stopped using it and went back to plan old x-rays or if tumours were suspected, used ‘air or other gases’. However, the Radiological profession had by this time ‘got a taste’ of using a dye in x-rays, yes it made it easier to read, remember, x-ray was still in its infancy so new products such as a dyes which enhanced the x-ray were exciting and at the forefront of radiological thinking, but were they safe to use, that was lost in all this excitement? Interestedly, when you read the medical journals of the time, it clear that Lipiodol was NEVER checked to ensure it was safe and non-toxic for humans when injected into the subarachnoid space. [Again how that came about is an interesting reading, again you will find that information in the link I shared earlier.] In fact, Lipiodol was NOT approved by the FDA for an injection into the CSF because of its direct link to [chemically induced] adhesive arachnoiditis, however, FDA approval for such use would come many years later, when the FDA were too lazy to read up on the history of Lipiodol and its relationship to [CI] AA. In fact it was never ever tested for such use, other than a small trial that killed ALL the rabbits it was tested on. In fact Lipiodol had been develop in 1909 and licensed in 1920 solely as an injectable substance to reduce pain in muscles. [same as Epidural Steriod Injection [ESI] today which comes to mind here] Sadly the question of was it safe? Did not come into the thinking of those using the dye initially, so a generation of sufferers like us [prior to Pantopaque] experienced the same horrendous abuse, just so the end user “could see the x-ray better”.
In May 1939, whilst Pantopaque was being tested on Animals, [1936 – 1941] Dr Dandy from the John Hopkins Hospital once ‘again’ pleaded with those still using Lipiodol TO STOP, he did so by publishing the following Medical Journal Article in the American Medical Association Journal it was titled: Concealed ruptured intervertebral disks ‘A Plea For The Elimination Of contrast Mediums In Diagnosis’, [no one listened]
Here is the front page of Dandy 1939 MJA.
Below if the full PDF copy of the Dandy MJA.
As you can see Dandy reports a 98% success rate in diagnosing Bulging Discs based on a patient history, and examination alone, NO lumbar puncture is required, an exploration of the region [operation] is preferable to spinal injection of air or iodized oil.
As Lipiodol had been found to cause [chemically induced] adhesive arachnoiditis most BUT not all end-users stopped using it, and the radiological profession commenced the search for a “inert dye”, [inert means chemically inactive] especially after another 1939 medical journal article was published written by a Dr Eric Oldberg in Surgery Gynaecology and Obstetrics the medical journal article was titled ‘A Plea for the respect for the tissues of the central nervous system’.
As there are only two pages of the article, I will place both pages here.
As you can see like Dr Dandy article, Dr Oldberg pleads with everyone to stop using oil base contrast medium Lipiodol with the following warning …’Anyone who has had perforce to dig about in the soggy mess which is the cauda equina of some unfortunate in whom five or ten cubic centimeters of lipiodol had been optimistically injected a year or two previously will understand this statement. Not only is the original disease still present, but a chronic, adhesive, chemical inflammation of the caudal roots has been engrafted upon it’… .
However I will not dwell on the Lipiodol History, or of the use of air or gases, for the reader can find more on the internet if they so wish. This Blog is about the second oil base x-ray dye Pantopaque developed which unlike Lipiodol was injected into tens of millions of Americans and likewise in many of the 107 countries worldwide where it was used not for 9 years as Lipiodol was, but for 56 years destroying hundreds of millions of lives and killing tens of thousands in its path.
After Steinhausen, Strain and Warren had completed the animal tests which as we know today showed that this experimental substance was highly toxic and furthermore, these multi animal tests showed it killed or seriously injured ALL the animals injected. However, this did not stop them, oh no, they now want to carry out Human Clinical Tests so they devised a way to do so, ‘they gave away samples’ to the Neurosurgeons that attended the 1942 Harvey Cushing Society Meeting that was held on the 18th, 19th and 20th of May of that year. This distribution of Pantopaque samples flies in the eye of the 1938 FDCA’s requirements for those wishing to obtain FDA’s premarketing approval must demonstrate their product is ‘safe’ to the FDA before introducing an imaging agent for use in U.S. patients. This did not take place, Dr. Warren took it upon himself to begin promoting Pantopaque to U.S. physicians by supplying them with these samples, disregarding the fact that he had NOT gained FDA approval for such.
The Harvey Cushing Society was later to become the American Association of Neurological Surgeons and since its conception in 1931 it was a Society for American Neurosurgeons to met on a yearly basis. Please see below a front page of Minutes of this 1942 Meeting where it lists all those that attended, please note who attended as they (or some of them,) will play a pinnacle role in the misleading of the acceptable recommended dose of Pantopaque, [LD50, which means lethal dose at 50% used] interestingly, whilst many attending received samples of Pantopaque at this meeting, others there had been receiving Pantopaque to use on its patients for more that a year.
The following day [on the 19th of May] at this Meeting a Dr William P. Van Wagenen from the Department of Surgery, Neurosurgery Division, School of Medicine and Dentistry at the University of Rochester and co-founder and first president of the Harvey Cushing Society presented a Paper on Ethyl Iodophenylundecylate Pantopaque below is an Abstract taken from the Paper, whilst not undermining anything of the reputation of Dr William P. Van Wagenen one cannot dismiss that the developers of Pantopaque and he came from the same University which was funded by Eastman Kodak.
PLEASE note below the recommended dose, 2 – 3 c.c. and the reasons for such.
The following is highly disturbing.
‘FOR THIS ILLEGAL PROCESS SEEN BELOW, IS ALSO EXACTLY WHAT TOOK PLACE IN AUSTRALIA’
After the FDA received a letter [Sept 1942] from a Mr. J.T. Fuess of Chemical Sales Division, Eastman Kodak Company, Rochester, NY, regarding the issue of Eastman Kodak’s reported interstate deliveries of Pantopaque to the “Military”, [My words, where in fact it was going to civilian Hospitals.] This letter was written by the Assistant Commissioner of the FDA, a P.B. Dunbar where he writes …’This refers again to your letter of September 4 in reference to Pantopaque. With the understanding that deliveries of this drug will be restricted exclusively to the military forces this Administration will not insist on compliance with the requirements of section 505 of the Act dealing with new drugs. Should you contemplate at any time entering into the ordinary commercial distribution of Pantopaque, [my words they already had, years earlier] it will be expected that the precise requirements of section 505 of the Act will be met. This will require the filing of a formal application with proof of the safety of the drug. If in lieu of filing of a formal application you elect to take advantage of section 505(i) and distribute the drug solely for investigational use by qualified civilian experts, it will be expected that the requirements of section 505(i), together with the regulations thereunder, will be met, including the labelling of the product with the statement “Caution: New drug- Limited by Federal law to investigational use.” Up to the present time we have had inquiries regarding the use of Pantopaque only from the Office of the Surgeon General of the War Department. Should a similar request be received’… .
HOLD ON — HOLD ON
Isn’t this back to front? Here the FDA is approving supply to the Military with a direction [seen above] that NO approval has been granted for Pantopaque to be supplied or used in the civilian sector without meeting the laid out requirements under section 505 (i) BUT such is being ignored, in fact, such has been taken place for at least a year.
- SO IN MAY THE DEVELOPERS SHARE PANTOPAQUE WITH NEUROSURGEONS.
- IN NOVEMBER BOTH THE ARMY AND NAVY RESPONDS TO STRAINS LETTER [BELOW] AND AFTER THIS
- THE DEVELOPERS INTRODUCE PANTOPAQUE TO THE RADIOLOGICAL PROFESSION, WHILST SOME ATTENDING HAD BEEN USING IT FOR MORE THAN A YEAR ON PATIENTS.
So after Dr Strain writes to the Military he receives a response on the 3oth November 1942 [18 months prior to it being licensed by the FDA] from the Office of the Surgeon General War Department (Service of Supply) and Surgeon General of the U. S. Navy Bureau of Medicine and Surgery Department of Navy in Washington D.C. These two letters which you can see below show that they are approving the “use” of Ethyl Iodophenylundecylate (also known as Iophendylate Pantopaque) without the direct knowledge to US service personnel [the patients] or the Military themselves] that it was ‘too toxic’ and dangerous, unlike the developers themselves.
For those that wish to know more about Ross T McIntire Rear Admiral Surgeon General of the US Navy due to the fact that he signed the above letter, as well as his LINK to others that were not only ‘watch keepers’ of the welfare of Americans health wise, but held very powerful positions to keep such quiet as CIAA starts to develop later, not only here in this country but worldwide.
Follow the link below.
This enabled the “establishment”, to promote the “safety” of Iophendylate byway initially of Military Hospitals and end-users, later to the regulatory authorities and finally the general community, and on hundreds of thousands of injured Soldiers, Sailors and Air Force personnel.
On the 30th of November, 1st, 2nd, and 3rd of December of the same year being 1942 the developers being Rochester University and Eastman Kodak misleads the Radiological Profession at the 28th Annual Meeting of the Radiological Society of North America by recommending a dose of 3 – 5 c.c. when using Pantopaque. This promotion of such a dose sets in motion TWO different recommendation of the Pantopaque dose, one for Neurosurgeons being 2·5 c.c. to 3 c.c. and one for the Radiological Profession being 3 – 5 c.c. [see below] taking it over the 3 c.c ampoules, which in turn and as may Radiologists reported, I quote: …”for it gives a better picture the more one uses”… End quote. This recommended dose to the profession that would be the greatest user of this dye would cause them to open another 3 c.c. ampoule to “get these better pictures“, its not long before Radiologists are using all of the two ampoules taking the dose now to 6 c.c. exactly what the joint developers wanted.
This increase of c.c.’s used lead soon to the manufacturers producing 6 c.c. ampoules, reporting the reason for such was due to the Radiological Profession asking them to do so, [‘in my belief a deliberate ploy to increase sales’,] without any knowledge of such a dose being safe to the patient. Evidence of this request by Radiologists will be available through a future posted video I will place here on this Blog showing the owner of the Company that Manufactured Pantopaque being Layayette Pharmacal Inc verifies such in a Video Court Deposition.
Here is that evidence of a recommendation of 3 – 5 c.c. dose to the Radiological Profession by the joint developers six months after recommending a dose of 2·5 to 3.0 c.c. to Neurosurgeons, was this a “misprint” well the next year on the 20th of April 1943 when the developers submitted their [first] NDA to the FDA as part of this new drug application [NDA] they submitted a two page document of the Technique for Myelography with Pantopaque, I will place that document following the referred to 28th Annual Meeting of the Radiological Society of North America evidence below.
[The following is taken from the Parisian Report with thanks]
…’In terms of the sponsors’ Pantopaque presentation in the abstract, it also appeared that the authors did not wish to accurately reflect the earlier Steinhausen dog data nor actual clinical experience described in the 1942 letter from Dr. Rigler in terms of his facility’s “unfavorable” clinical experience. [A copy of that letter can be found further down in this Blog] There appears to have been a conscious decision in 1942 by the authors to disregard Dr. Rigler’s clinical findings, [referred to earlier] an ‘intentional disregard‘ of the requirements that had been detailed by the FDA, an intentional disregard of clinical ethical conduct, and failure to provide physicians with complete and accurate, and truthful outcomes documented for Pantopaque through both human and animal experience. The abstract misrepresents the scientific facts for Pantopaque as known by the authors in 1942 by containing “misleading” statements about the long-term effects of Pantopaque in the dog studies: The new medium is more fluid than the iodinized oils and may be injected with ease. With dogs intrathecal injection of 3 – 5 cc causes a transitory pleocytosis with cell counts of 200 to 700 (mostly polys). Histological sections taken during or after this transient reaction period show a collection of the medium under the meninges with a localized foreign body response around the small droplets. Consecutive radiographs demonstrate that the preparation is rapidly absorbed at first, but more slowly as the medium becomes fixed in position. Nevertheless, amounts of 3 – 5 cc are absorbed nearly completely in the course of a year with little or no evidence of residual reaction. Parallel experiments with iodized poppy seed oil in dogs show somewhat more extensive pathology with little evidence of absorption. Clinically, the new medium has been found to facilitate greatly myeolographic examination. In addition to ease of injection, the preparation flows readily immediately after injection and may be removed without difficulty. The entire examination including injection and removal, can be completed in fifteen minutes’… .
As I say in my Australian Blog from a • – DOT TO A DASH • – © this misleading direction of dosage especially to the Radiological profession [being the main end-users] will create the human destruction we know today and of which I am trying to expose.
At this Meeting as I posted earlier the following MJA [see below] was presented, I will place the front page here and the full copy as a PDF below that.
As you can see this MJA which I posted earlier when I compared it with Steinhausen Thesis is Numbered III and also written by Steinhausen himself. This MJA is one of a collection published over the next 5 years by Dr Strain and others, I have decided to place them all here together so the reader can, if they so wish, read them as a collective to get a better understanding of ‘how they mislead’ not only the FDA but also end-users be it Neuroradiologist or Neurosurgeons and “others”.
Here below is the full MJA as a PDF.
We have to digress for while for much is happening at this time being 1941 to 1944, American enters the War and “some” Businesses rub their hands in glee, as its well know with the Business sector War brings with it an opportunity to make money, and sadly this is one of them.
As you have read, the developers introduce this new x-ray dye FIRST the American Neurosurgeons, why them do you ask, well the President of the Neurosurgeons Society as I mentioned early was also great friends with the developers from the University of Rochester where the chemical formula was “hatched”. So when the President of the Neurosurgery recommends it, they all not only listen BUT believe as well taking away the samples given to them ‘to try’. The developers next stop was 6 months later to the American Radiological Society which also I wrote about earlier, where they not only introduced this new x-ray dye BUT mislead them by using the animal test [dogs] dose as a indirect recommendation of a dose on humans by sharing with the Radiologists there. Next, these samples were then tried and reported back to the developers, BUT were they, was the contents of the letters [which I will post below] written by the end-user themselves, or did they just sign the letter which was penned by “others”. Why do I say this, and again this is critical for you to grasp, now that this ‘too toxic radiographic dye’ had been “tested” on patients, was the true outcome that what was reported, used? I ask that you examine CAREFULLY the selection of letters used to support the developers NDA to the FDA, these are the only one submitted to the FDA what happened to the rest, what did they say, were they supportive? Or did they say otherwise? Like the letter from a Dr. Rigler, of the University of Minnesota Hospitals in Minneapolis who wrote to Dr. Warren On June 26, 1942 reporting his facility’s negative clinical experience with Pantopaque for imaging their patients, a letter that was not included with the others submitted to the FDA that I have posted below. Dr. Rigler did not provide “favorable” information to Dr. Warren regarding the performance of Pantopaque in human patients. Dr. Rigler indicated that it was his opinion, as well as his staff’s opinion, that the material mixed too readily with the spinal fluid and did not improve imaging quality. He also indicated that he felt that the material was extremely difficult to remove. Dr. Rigler wrote to Dr. Warren of the experiences of his staff with Pantopaque: We have completed some myelographies with your Pantopaque which you were so kind to send me, but for our purposes we have found it somewhat unsatisfactory. Doctor Peterson, who has been doing this work here for some time and has had a considerable experience with both air and lipidol, feels that the material mixes much too readily with the spinal fluid so that a clear cut picture cannot be obtained. Obviously, in a case of a block of any degree, it would be entirely satisfactory, but if you are trying to demonstrated herniated disc or tumor without complete block or arachnoiditis, the normal miscibility of the material would be most confusing. Furthermore, he found it extremely difficult to remove. Large quantities of spinal fluid were removed by the usual methods that we use in removing lipidol, but he was quite unsuccessful. I am sending you illustrations of two cases, one done with lipidol and the other with Pantopaque, to give you some idea of the contrast, both the original films and the amount of opaque material left after attempts at removal. You will note that in the case of lipiodol, using the maneuver of Kubik and Hampton, all except a very few droplets were successfully removed whereas in the case of the Pantopaque most of it all remained!!!
Before we go to take a closer look at these letters of support, I wish to draw your attention to the following, whilst Steinhausen submitted his Thesis in 1941 the animal studies were carried out from 1936 by Dr Strain, Dr Stafford and Steinhausen at Rochester University. However, without gaining permission of the FDA to trial Pantopaque they went ahead and done so, the first letter I have been able to obtain shows that it was being used [tested] in the latter half of 1941 without I’m sure the Patients knowledge or giving permission, the belief that it was being trialled for other procedures is also correct.
Interestedly ALL of the letters are typed using the same font, well in 1941-2-3 this would not be so surprising for all typewriters would be alike, and especially in Hospitals [possibly bought in bulk] what is MOST disturbing is this, in almost all of these letters the e & n when they follow each other [as en] are the same, the e key has a slight bend placing it closer to the n than all others, and this can be seen in many of these letters of support. It is my contention, that the developers typed them and had the Neurosurgeon sign them, in so doing, promoting Pantopaque as safe and absorbable, when of course we know, and so did the developers at that time, that this was not the case.
Please see these letters here below and I ask that you enlarge the print and YOU decide.
Whilst Pantopaque was being promoted, Eastman Kodak received a request from Lafayette Pharmacal to use the name Pantopaque which Eastman Kodak had the Trademark to, [or did they?] as it was they that produced the chemical Ethyl- Iodophenylundecylate with the assistance of initially John Plati and then Theodore Steinhausen. As you can read in Eastman Kodak’s reply [see below] they agreed that Lafayette Pharmacal could use the name Pantopaque for this new dye, especially as Lafayette Pharmacal were in the process of testing this chemical on a range of Animals. As you are aware these animal tests showed this substance was far too toxic for human use, were posted on this Blog earlier. Its interesting to note that Eastman Kodak does not give Lafayette Pharmacal exclusive rights to use the name Pantopaque.
What is interesting is this, Eastman Kodak as you can see in the letter above gives permission for Lafayette Pharmacal to use their “Trademark” Pantopaque this letter is dated the 8th of Jan 1943. However, as you can see by the image below Kodak had NOT yet Patent/Trademarked Pantopaque this was done on the 19th of Jan 1943 11 days later. What I ask the reader to take on board is this….
The Trademark of Pantopaque was for
QUESTION…. How did Contrast Medium get added to this Trademark. and when???
I have no idea YET.
Lets move on, but we will return to this when I get answers from the US TradeMark regarding that question, asked of them yesterday. 14/2/2016/
Between 1943 and 1945 a collection of medical journals were published by some of those that attended the Harvey Cushing Society meeting seen above, mainly those from a Military standpoint. Further these Military based MJA’s mainly [95%] came from one Hospital Walter Reed Hospital, and the reason will become much clearer as you read further into this Blog. Each of these MJA’s I will also post in full however, I will first post a copy of the front page of each above the full PDF copy. Only one of these MJA’s were published prior to Pantopaque General Marketing License, the date being the 1st and 2nd of December 1943 Titled: Myelography with Pantopaque and New Technic for its Removal. Interestedly, within this MJA [see front page right column 15/16 line from the bottom] it reports the following …’3.c.c a sufficient quantity’… . It is important to note that these MJA’s ALL except one [the Dr Spurling Article] uses the developers recommended dose of 3 c.c., however, Dr Spurling MJA uses 3.5 c.c now lets examine this closely, to use 3.5 c.c one needs to open a second amploule of Pantopaque, which makes no sense, wasting 2.5 c.c. this is not only illogical but due to a shortage of Pantoaque because of the war, such wastage would not happen. So what could be the reason? I believe Dr Spurling entered 3.5 c.c’s [as you can see on page 564 table 1.] he did this to assist the developers change the • – DOT TO A DASH • – [dose] later and bring such in line of that which Radiologists were recommended to use, by doing, this doubling of dose used also doubles sales. $$$$. What I cannot find to date is ANY FDA approval to increase this dose used, to date, all my FOI applications for access to such has gone unanswered, was there any FDA required human clinical studies carried out? Of great concern to the writer is this, in 1951 large volume dosage took place for full spinal column x-ray using 12 – 30 c.c. and at least one using 100 c.c. where I believe the patient died, no autopsy took place.] So as I mentioned earlier there were a selection of MJA’s published by doctors at Military Hospitals all but one using 3 c.c. Whilst reviewing these MJA’s regarding what dose was used, something struck me, and I am sure will be of interest to you the reader. It seems all these MJA’s were penned by different doctors UNDER Lieutenant Colonel Roy G. Spurling at Walter Reed Hospital, so whilst it portrays that a wide selection of Pantopaque end-users from different Hospitals etc were evaluating it on patients, that is incorrect, the initial introduction and human trials all took place at one Hospital the Walter Reed under Spurling. It was the later individual trials at each author’s Hospital. [With the samples given to them] and “guided” by their BOSS Dr Spurling.
Furthermore, one must consider the following, Dr Spurling at that time was a very close friends with a Dr. William P. van Wagenen, so who was Dr William P. van Wagenen? The plot thickens.
Dr. William P. van Wagenen
In 1931 they both with two others formed the Harvey Cushing Society, as friends do, he, Dr Spurling had 3 years earlier recommended Dr William P. van Wagenen for the post of Assistant Professor of Neurosurgery and Chief of the Neurosurgical Service at the recently opened Medical School at the University of Rochester in 1928. [Where of course Pantopaque later was concocted] This close friendship for at least 15 years [1928 – 1943] was the link between Spurling at Walter Reed Hospital and Wagenen at Rochester and the Pantopaque clinical Human trials on unsuspecting War injured Military personnel. Did this very close friendship go one step further in the promotion of Pantopaque by encouraging selected fellow Neurosurgeons and Radiologists working in these Civilian Hospitals to do likewise, especially by encouraging or advocating the use of a dose of 3·5 c.c. like Spurling had “used successfully”. Soon the dose being used was between 2 – 5 c.c. the 2 c.c. for use outlining the brain and ventricles and up to 5 c.c. for spinal myelography. Soon the Radiologists were “pressing” Lafayette Pharmacal [the manufacturers] to produce a 5 c.c. ampoule, seeing an opportunity they manufactured a 6 c.c. as well as a 12 c.c. ampoule after gaining FDA approval, however, again there is NO evidence of the FDA checking such dosage was ‘non-toxic’ for use on humans, I am still awaiting documented evidence of such approval by the FDA under FOI. History shows us that neuro-radiologist, neurosurgeons and the like were only concerned that the use of oil base dyes currently being used shows up later in x-rays and left them open for legal redress. So believing the Maufacturers that Pantopaque was an absorbable product so any later legal redress was mute, for end-users had experienced such with Lipiodol. When one re-reads the MJA’s from Walter Reed Hospital [1942 -45] over then period where Pantopaque was being tested and trialled its very clear that this was a well orchestrated plan ‘between specific staff members of the School of Radiology’ and Spurling and others at Walter Reed Hospital’, ALL funded by Eastman Kodak.
Here are 8 of these Military Hospital MJAs, I will place the front page and underneath, the full article as a PDF file.
The first MJA below shows that they believe that Pantopaque is ‘slowly absorbed‘, whilst today we know such does not happen its just the opaqueness subsides, portraying ‘that Pantopaque has absorbed’. Further, the authors of this MJA states [on first page] that 3 cc was a sufficient quantity and in fact, that was the dose used and reported not only in this MJA but shared at the 29th Annual Meeting of the North American Radiological Society held in Chicago on the 1st and 2nd of December 1943, in front of hundreds of their members when it was read 6 months PRIOR to Pantopaque being approved for General Marketing. So the contents of not only this MJA but others below and elsewhere will have, and did have an enormous bearing on the FDA approval for General Marketing, for as you remember the FDA was in its infancy stage at that time and was relying on the Medical profession and related experts for guidance. However, one can see as one reads all the related MJAs at that time, end-users, were captivated and ecstatic of what they now had “a promoted absorbable x-ray dye” to use at last, especially with the previous failure of Lipiodol which was found to cause Chemically Induced Adhesive Arachnoiditis in patients injected and they in turn, being sued.
What must NOT be missed here is why they were ecstatic, it had nothing to do with the ‘safety’ of the patient it was to do with the fact that Pantopaque was being promoted as being an absorbable product, removing the risk of them ever being sued in the future.
And if you cant see it, it ‘ant’ there, eh!!!
These specific Medical Journal Articles below are most interesting for one of them is NOT from Walter Reed Army Hospital but from a Navy Hospital, [1.] whilst they record certain points that was not referred to in the MJA’s penned by the subordinates of Dr Spurling much is them same. I will cover a few here. They make reference to the similarities to Lipiodol if Pantopaque was only partially withdrawn, they make mention to the fact (Pantopaque. …’it is usually possible to remove all but a few tenths of a c.c.’… . They write about extra-arachnoid injection [in error] and its problems to the patient. They write about …’the lack of a complete satisfactory contrast medium and improvement in clinical diagnostic methods’, saying there has been a recent trend towards exploration for herniated nucleus pulpous [disc] on the basis of the clinical findings alone’… they go on to say …’their own personal experience has reached a point where they believe that their clinical diagnosis is just as accurate as the roentgenoscope diagnosis obtained by the use of radiopaque oil’… . They then make reference to a MJA by Shinners and Hamby [which you can find in the Journal of Neurosurgery dated 1944 1 : 117 – 122 titled; The results of surgical removal of protruded nucleus pulposus in the lower lumbar region.] where Shinner and Hamby states …’All contrast studies were abandoned since it was realized that the results were not only confusing but often misleading’… …’Dr Camp found air to be 90% accurate’… and went on to report …’In spite of the excellent localizing value of Lipiodol there have been numerous objections and disadvantages to its route use. These include difficulty in removal; very slow rate of absorption with subsequent possibility of encystment, nerve root irritation and medical-legal complications’… They then state that Pantopaque ‘appears to be the best contrast medium thus far available’… …’Symptoms of meningeal irritation may occur after an interval if Pantopaque extends into the basal cisterns’… . However, this article does promote Pantopaque, however, it’s clear that there was no follow up of the patients. As I have reported elsewhere, its due to dose used above 2.85 c.c. and how much if any was removed afterwards. With most of those that had it aspirated a lesser reaction takes place, however, once a second Pantopaque Myelogram [very common here in America] takes place due to many of the patients complaining later of unusual pain and disability since their first injection. This residual amount that was left in due to it being oil and then added to the second amount left, the patient is now at serious risk of developing CIAA. This residual Pantopaque and multi-build up is the cause of most CIAA sufferers exposed to Pantopaque here in this country. Of course in many other counties where end-users never aspirated due to them being unaware of the need to remove after the procedure was completed, [as I write this, I find such hard to believe, due to their previous awareness of Lipiodol] however, in GB , Europe and many other countries it was never aspirated, and due to such Chemically Induced Adhesive Arachnoidits develops more quickly, but due to the original spinal issue the patient has, the link to the dye goes ‘unchecked’ or should that read, ‘unspoken‘, until much later, when the statute of limitations has expired, the deliberate ploy of the Developer/Manufacturer/End-user.
One of the MJA below reports once again on patients injected with Pantopaque at Walter Reed Army Hospital, and like all others they support that which their “boss” Dr Spurling wrote, the previous year. So what do they say? Well quite clearly they report on the dose used being 3 c.c. within the first paragraph. Interestedly, [especially for the writer, for I had a massive chest infection with a unrelenting cough and pneumona, when they did my myelogram] they report in the MJA referred to the following …’I asked the patient to cough, as the patient coughed, I saw a marked and bizarre change in the pantopaque column. It appeared to extend in all directions like a star burst’… [and] …’it was once realized that the oil had entered the venous system’… …’two minutes later an x-ray showed that the oil had reached the skull, chest, heart and abdomen’… . The author of this MJA further states and I ask that you read this very carefully, for it shows Dr Strain lied to this Doctor, it seems that this Doctor spoke to Dr Strain about what had happened and Strain told him the following, he had …’slowly administered 8 c.c. of Pantopaque intravenously to dogs weighing 15 -20 kg without serious results’… .
This intrigued me, for I was sure this was NOT the case, So I went back to that study Strain referred to, and found this!!!
You can find this in the animal studies I place earlier, this specific study is number 6 titled: Acute Toxicity of Ethyl-iodophenylundecylate by intravenous injection in Dogs and Rabbits.
Here below is that first of the 8 Military Hospital Articles MJA referred to above.
Sorry about the quality of the following MJA, which whilst was published in the British Journal of Radiology contents are very interesting whilst the state that they would prefer to use 5 to 6 cc or greater, BUT state that 3 c.c. is adequate in most cases, which complies with the recommended dose on the 1944 initial Product Insert.
[Anyone that has a clear copy of the MJA below I would appreciate]
MJA 1944. (2.)
Full MJA’s as a PDF file
MJA 1944. (3.)
Full MJA’s as a PDF file
MJA 1944. (4.)
Full MJA’s as a PDF file
MJA 1944. (5.)
Full MJA’s as a PDF file
MJA 1945. (6.)
Full MJA’s as a PDF file
Lets move on to the next two MJA’s whilst we can see this was not written by subordinates of Dr Spurling at Walter Reed Army Hospital, it important that I first need to point out that this MJA was read at the 1945 Annual meeting of the Radiological Society of North America the following year after Pantopaque was introduced to them in 1944, remember. The MJA opens with the following …’Numerous articles dealing with the use of Pantopaque in myelography have appeared in the medical literature in the past 3 years.’… . The authors refer to the use of 3 c.c. BUT then gone on to say …’Recently we have used 5 and 6 c.c in several instances. we believe that the additional amount is of advantage’… [to whom?] ...'(1.) for better filling of what is apparently a narrowed canal (2.) for better filling of the caudal sac, and (3.) for the simultaneous visualization of several interspaces (Fig 12).’… . [Again, this shows the blasé of end-users increasing the dose used without any knowledge of such was safe, and approved by the FDA.] The authors refer to ‘Sources of Error’ especially in the extra-arachnoid area when using the injection of oil contrast medium, making mention that …’oil injected in the 4th lumbar interspace often rapidly reaches the lower thoracic region, as illustrated in Figure 1, A’… . Interestedly, a sub heading in this article seen on on page 41 titled: Adhesions. refers to the fact that the authors …’have had occasion to do myelography on patients from whom a ruptured disk had previously been removed, who had symptoms suggestive of recurrence’… [my comments, CIAA] …’The myelography showed irregular deformity of the oil column. At operation, extensive scar tissue was found, producing pressure on the nerve roots, but no recurrent disk rupture. These cases present one of the most difficult diagnostic problems’… . Considering only 10 years earlier Lipoidol was doing the same thing, why wasn’t the alarm bells ringing? My final MJA in this section seen on the ‘right’, again from the Walter Reed Hospital using 3 c.c. and making reference to the fact that …’Pantopaque myelography is basically a simple procedure’… …’In fact, the procedure is given only casual consideration in the presence of the patient’… …’the needle is never taken out until removal is completed, because if the needle is withdrawn, oil or fluid frequently escapes through the needle hole into the subdural or epidural space’… . For those reading this, that had Myodil injected and had the needle removed because it was standard practise to leave in, would NOT the oil THEN have done likewise, in YOUR case??? This ‘frequently escapes through the needle hole into the subdural or epidural space’ may answer one of the major questions of how CIAA developed elsewhere in the body.
MJA 1945. (7.)
Full MJA’s as a PDF file
The final MJA I wish to share here as part of this collective of 8 MJA’s, I came across later and though that it too would be benificial to the overall story of
MJA 1945. (8.)
Full MJA’s as a PDF file
It is clear, [like today] that there are NO follow-up evidence which is independent on the adverse reaction of Pantopaque on patients including the hundreds injected at Walter Reed Hospital. I mentioned earlier a MJA reporting on how one removes oil contrast medium [Lipiodol and Pantopaque] after the procedure was completed, [there are others available on request, especially the Classical MJA of Kubik and Hampton (1941) titled: Removal of Iodised oil by lumbar puncture available within the New England Journal of medicine 224 (11) pages 455 -457, here is a copy.
The following MJA’s farther below ALL came from the Water Reed Hospital although, its difficult to sight the source without reading the MJA or tracking down the specific doctor/s [at that time] and where they were at.
The first MJA that is specifically related to Pantopaque was written Captain George M. Wyatt and Lieutenant Colonel Roy G. Spurling. [Below]
Dr Spurling was the first Chief of Neurosurgery at the Walter Reed General Hospital and organised the neurosurgical service for the United States Army while serving as Assistant Chief of General Surgery. he was posted to London in March 1944 with the responsibility for neurosurgery in the European theatre of War. [The MJA’s referred to were written a year prior to being published which was pretty standard at that time, penned before Spurling left for London. [UK] My contention is, Spurling due to his position at Walter Reed Hospital created an “understanding with others” that Pantopaque was fine, [in 1942] not so much because it was [for we now know it wasn’t] BUT to create a persona that it was, so ‘the powers to be’ would approve it for the war effort. This also maybe the link to Myodil as he was [as you can see above] posted to London in the late 1944 with the responsibility for not only the knowledge of Pantopaque, but the ‘spill’ that it [as in his MJA front page last two lines] …’absorbed at a significant rate of speed safe’… and the promotion of the 3.5 c.c. dose which can be found again in his MJA on page 564 in table 1. Finally, note subtitle of this MJA ..’Notes on Absorption following Myelography’, drawing the reader to the belief that Pantopaque absorbs within the subarachnoid space, rather than today we know it just loses its opaqueness.
So below is the front page of Spurlings MJA
Titled: Pantopaque…’Notes on Absorption following Myelography’.
I have posted here below a copy of table 1. and dose used being 3.5 c.c.
And now the full PDF copy of that MJA seen in Blue below.
I have decided to re-post the Steinhausen medical journal article below so you can understand how all this happened for as you can see it was presented 2 months later in July 1944, the MJA to the right was published in September of 1944. Remember all these MJA will have a full PDF copy of the MJA below this front page, to increase the size double click on the image and go to the bottom right where you can further click to obtain a full size copy and then if you need to further increase press the magnifying glass, if you cant read it them may I suggest ‘spec savers’. I have shared with you or I should say Dr Charles Burton did ‘the differences between Steinhausen Thesis to this MJA, I would advise you to print out and fully understand the differences between the two. The MJA below to the right reports like all others [other than Spurlings MJA] a usage of 3 c.c. of Pantopaque. [see page 246] its interesting to read within this article [and I have seen in many others in my travels] the author refers to the patients conditions [a protruded intervertebral disc] as a disease, [see last page left column bottom in Summary] ONCE the Myelogram and meningitis reaction has taken place. Again interesting!
I will not comment of Steinhausens MJA for its been done earlier, however, will share a little regarding the MJA on the right for it contains some ‘interesting remarks’ in support of Dr Spurling “findings”. See page 251 left column 2nd paragraph where the author Major Benjamin Coleman states …’Air was the contrast substance suggested and used. it is still staunchly advocated by a few’… below 3rd paragraph …’Of late there has been a great decrease in the use of Lipiodol in spite of the excellent use which it has been made of in the past. This may be due in part to occasional clinical reactions, the frequent difficulty encountered in its removal and the aggravation of symptoms which frequently occur when it is incompletely removed’… . Now to the right hand side when he makes further comments on the benefits of Pantopaque, for the end-users that is. [See 2nd paragraph] …’It maintains itself in a homogeneous column, which fills the nerve sleeves very readily’… …’late there has been a great decrease in the use of Lipiodol in spite of the excellent use which it has been made of in the past. This may be due in part to occasional clinical reactions, the frequent difficulty encountered in its removal and the aggravation of symptoms which frequently occur when it is incompletely removed’… . Now to the right hand side when he makes further comments on the benefits of Pantopaque, for the end-users that is. [See 1st paragraph] …’It maintains itself in a homogeneous column, which fills the nerve sleeves very readily’… . NOW to the LIES. See 2nd paragraph …’The material has been proven to be NONTOXIC both only experimental and clinical use’… …’In most of the patients all but a few droplets has been removed. Occasionally, because the needle was somewhat off centre, it was found impossible to remove any or all of it’… . further down he states something very interesting …’We have had no follow up studies longer than 6 months after the original examination and therefore cannot attest to its absorbability. Since the material IS SO innocuous and unproductive of reactions, the question of absorbability seems unimportant’… . This remark of the material ‘IS SO innocuous and unproductive’ creates a perception of other end-users reading this, that any adverse reactions must be their fault, so nothing is said to the patient. Finally, and this is a remark often made by those directly or indirectly involved in the Myelogram, they call the CONDITION of a protruded intervertebral disc a DISEASE. See Summary page 252.
I have decided to add here 2 more MJA’s both dated 1943, yes, I have ‘skipped along somewhat’ I will return to 1942 shortly, BUT both MJA’s show some interesting facts that need to be shared here.
Here below is the front page of the first MJA taken from the US Army Medical Bulletin dated 1943 it will be followed by a full copy of the article as a PDF file.
On page of 4 of the article [marked page 30] above you will find the following …’Where the diagnosis cannot be made definitely on the bases of the history and physical examination, myelography is indicated. Pantopaque is the medium of choice. It is removed at the end of the examination, even though it has been found not to cause irritation when left in. Pantopaque myelograms are made routinely at Walter Reed General Hospital on all disc cases in which surgery is contemplated. They are done to verify the diagnosis and to localize the lesion accurately. This permits removal of the disc with the least possible disturbance to the spinal weight-bearing mechanism It must be remembered that a herniated disc occasionally may be missed on myelographic studies. These herniation’s are incomplete and produce only a temporary bulge in the annulus fibrosus with the patient in certain positions. Also multiple lesions may occur. A large protrusion at the fourth interspace may block the canal and prevent accurate visualization of a fifth lumbar disc. Surgery without myelography is justified only when the patient presents the classical history and neurologic findings’… .
What is disturbing here and adds weight to the cause of CIAA is that the suggested dose is slowly being increased or promoted. Furthermore, the seed is/has been planted that there is NO reason to aspirate, and it is fine to leave in, by reporting the following …‘even though it has been found not to cause irritation when left in’… by mentioning Walter Reed Hospital all in the same paragraph such a belief is being indirectly linking by other end-users to what the leading Army Hospital in the Country is doing at that time, “if its ok there, I can do likewise” especially, as it takes as long to aspirate as to carry out the Myelogram or Diskogram, in so doing, saving time and of course money.
The second 1943 MJA which you can find below is interesting especially on page 153, this MJA’s was again penned by Dr Spurling with a Dr Thompson and as you can see on this page they recommends using 3 c.c. Whats going on? well its very clear to the writer of this Blog, Spurling whilst using 3 c.c. at Walter Reed in 1943 but had promoted the dose of 3.5 c.c in December 1942 to the Radiological Society, but reverts back to 3 c.c. in his 1943 MJA which you can see below, but once again he promotes 3.5 c.c. in his 1944 MJA what’s going on you may ask? Well, notice the 1944 date, its submitted for publication one day AFTER Pantopaque was FDA approved. So whilst he instructed his ‘mates’ his fellow neurosurgeons to use 3 c.c. as Stain Steinhasen and Co did. Remember they recommended 2.85 c.c. as the dose ‘safe’ in humans leading to the development of 3 c.c. ampoules. Spurling instructs the Radiological Profession to use 3.5 c.c. ‘the plot has been set’ by him and ‘others’ to increase usage now the FDA has approved its use, how many times would this “increase of dose that place” well by 1952 they were recommending up to 30 c.c. and as I reported earlier one case of 100 c.c. ‘patient died of course!!!
Here’s that 1943 Spurling MJA taken from the US Army Medical Bulletin first the front cover, then the full PDF copy.
As you will appreciate, its impossible to write this in chronological order as certain points need to be reinforced by a ‘collection of evidence‘ such as those letters and MJA’s above which range from 1941 to 1945 and other important facts need to be shared. However, whilst I will try and write this ‘by date form’ on occasions such will apply.
Ok, lets go to 1943.
Here is the copy of the 20th of April 1943 Technique for Myelography with Pantopaque submitted by the developers [their first NDA] to the FDA as part of this new drug application. Interestedly, you can see they refer to the dose being 2 – 3 c.c. [being the dose initially recommended,] BUT remember!!! They have reinforced the dose of 3 – 5 c.c. to the end-users.
I have finally tracked down a copy of the circular requested by the FDA [see below] its consists of 5 pages but the first page is missing but a copy of that first page will be placed here, once I receive it from America. This circular has a selection of headings, which consist of the following as listed: Pharmacology, Technique for Myelography with Pantopaque, which has the following sub-headings: Injection of Pantopaque, Fluoroscopy and Radiology, Removal of Pantopaque, [making mention of Kubik and Hampton MJA, which I posted earlier. [In full] Also as a subheading within this Kubil and Hampton MJA found under Technique for Myelography with Pantopaque is reference to After-Care of Patient, followed by Side Effects, then Contradictions and finally, Limitations. Before I go through them the Headings and sub-headings its important to point out the following NO ‘RELATED’ ANIMAL STUDIES HAVE BEEN SUPPLIED BY LAFAYETTE PHARMACAL TO THE FDA AS REQUESTED/REQUIRED. Evidence of such disregard by Lafayette Pharmacal and Eastman Kodak etc will be shared with you using historical documentation later into this Blog. Ok, lets look at what is said in this circular by the Applicant being Lafayette Pharmacal, the first section Pharmacology: I am disregarding the comments on dosage [first 10 lines] you can see if they are the same as reported in the animal tests listed above. Lets go to the first of many lies given the first is at line 10 – 12 where they state …’no toxic phenomena have been observed, however, following intrathecal injection in rabbits and dogs even when massive doses have been administered’… . [I would like to remind you of what Lafayette Pharmacal reported in these Dog and Rabbit Tests 3, dogs died of the 55 tested all developed meningitis and cysts as soon as injected] See tests above for yourself. Please note this 1969 Dog test whilst they used 55 dogs all but 4 were injected into the dogs neck, of the 4 injected into the lumbar area one died. Also, there were NO intrathecal injection in Rabbits as reported in Lafayette Pharmacal Circular submitted to the FDA only intrauterine, interpleural, and intravenously injections took place, again see these specific rabbit tests above, .all died
Provisional Specification prior to Pantopaque FDA Application for General Marketing Approval. [submitted October 27th 1943]
Please note the last paragraph above…’The product shall give satisfactory results when assayed by intrathecal injection in dogs as described’…. This was submitted as you can see on the 27th of October 1943 and was used as part of Eastman Kodak/Lafayette Pharmacal submission to the FDA, and was relied on to gain their final 1944 FDA General Marketing License for Pantopaque application. The following year, Dr Strain on behalf of Rochester University notifies Lafayette Pharmacal in writing [see farther below in the Blog a copy of this two page letter] that …’for some time we have felt that the intrathecal assay was valueless, and it now has been found that the production of fever or of slight temperature elevation appears to be due to the Nembutal rather than to the intrathecal injection of ethyl iodophenylundecylate’… . …’Accordingly, it is proposed to eliminate this intrathecal assay as part of the specifications of ethyl iodophenylundecylate (Pantopaque) and to control the purity by narrowing the chemical and physical specifications’… . …’40,000 ampoules of Pantopaque have been distributed, and the consensus of publications, a list attached, uniformly has been that clinical reactions are seldom seen following the use of Pantopaque for myelography’… . …’If you feel that the proposal is in order, will you submit the material to the Food and Drug Administration’… . Signed William H Strain Associate in Radiology.
Just to put this in perspective, once the FDA started to enforce the reporting of any adverse reactions seen this ‘seldom seen reactions’ exploded, the question always asked of me is …’was there any Adverse Reactions to Pantopaque reported to the FDA in ???? year? ‘… . Well the FDA holds a 40 page report showing 82.3% of those injected with Pantopaque developed [Chemically Induced Adhesive] Arachnoiditis. How many WASN’T REPORTED!!!.
Here is one of those 40 pages.
Its important to be aware that Eastman Kodak Initial FDA New Drug Application for a Pantopaque General Marketing License was REFUSED due to it being TOO TOXIC based on the initial animal tests provided, which I have said earlier were NOT those that showed Pantopaqur to be way too toxic for use on humans. However, less than a month later the FDA approved it, and it seems even today, NO ONE cares or questions how this was allowed to happen.
Well I do,
and based on the contents of this Blog it is hoped other will also and will want answers too.
LETS MOVE ON.
On the 23rd of July 1943 Lafayette Pharmacal submitted an Application with the Federal Security Agency [FDA] in Washington D.C. They state that the name of the new Drug is Pantopaque to be purchased from Eastman Kodak Company to be packaged by them for X-ray distributors. A copy of that application can be seen below, they list within 6 Points to support their application [I will not them here, for its easy for you to read yourself, however, what is noticeably missing is the results of the Animal Tests although they maybe past of Point 1. [I will check] This application was signed by the then owner of Lafayette Pharmacal, William Bucke.
On the 7th of August 1943 [see a copy below] Lafayette Pharmacal received a reply from the Federal Security Agency in Washington D.C in regards to their Pantopaque New Drug Application. Stating that no animal studies had been included in their application other than a abstract of a paper that was presented at the 28th meeting of the Radiological Society of North America. [As like in Australia almost thirty years later,] They informed Bucke that to appraise the safety of [Pantopaque] these animal studies would be required, and it would be also necessary for them to review detailed reports of pharmacological experiments carried out on Pantopaque. They further required studies of the acute toxicity in at least two species of animals, both when the product is given intrathecally and intravenously this was due to Lafayette Pharmacal indicating that Pantopaque …’may be absorbed from the spinal canal into the systemic circulation’… . They being the Federal Security Agency also required information with regards to the rate of absorption and the effects that Pantopaque may exert on vital organs and on important physiological functions of the body. In the last paragraph, the regulators ‘suggested’ that Lafayette Pharmacal delete from the label [which had been provided to the regulators] the so-called “prescription legend” and include is the marketing package a circular setting forth the indications, dosage and contraindications. …‘This circular should be submitted as part of the application’… This letter was written by Walton Van Winkle Jr. M.D. Acting Chief Drug Division Federal Security Agency.
Here is that letter below.
Two days later the owner of Lafayette Pharmacal acknowledges receipt of the letter above stating …’the data will be forwarded at once from the University of Rochester’… . Naturally, whilst there is no doubt that these animal tests were carried out at Rochester University this confirms it in writing. Below is a copy of that letter.
On the 12th of August 1943 Dr W. Strain from Strong Memorial Hospital [pictured below] rang Dr Walton Van Winkle of the FDA Drug Division in regards to his request for data on the safety of Pantopaque.
This long distance phone call was ‘written up’ by Walton Van Winkle which I have obtained a copy, I will place here an overview of its contents and a full copy below. Strain informs Winkle that he would furnish him with the data relative to animal experiments which he had performed. He stated …’that he did NOT have very good figures on the acute toxicity and felt that the obtaining of any adequate data regard to the toxicity by ‘INTRATHECAL INJECTION WOULD BE DIFFICULT’… . [ My words, naturally it would be difficult to provide data on acute toxicity, when the animal data shows chronic toxicity!!!]
In October of the same year on the 20th to be exact, [See copy below] Dr Strain visits Walton Van Winkle Jr. M.D. Acting Chief of the Drug Division at the FDA and informs …’him that he has nearly completed all the animal studies requested and they should be shortly submitted by Lafayette Pharmacal Company’… . Then Dr Strain inform Winkle …’that he is working on a couple of new radio opaque media, one an oral preparation to be used for visualization of the gall bladder and another for a suspension of an iodinated organic compound to be used for gastro-intestinal examination’… . This is not only to reflect away from the Pantopaque animal studies still outstanding but as you are aware when they used Pantopaque for such procedures at test level, it was unsuccessful, however, these “new media” referred to ends up being Pantopaque, how is this??? Furthermore, whilst they referred to these animal tests NO mention that they are testing it illegally on humans, be it our war injured Military or Civilians. As you will see a little later the developers inform the FDA prior to approval of a General Marketing License in 1944 that they have used it on approx. 40,000 patients.
Found were these FDA notes of Walton Van Winkle, William Fassett and Co of the FDA regarding their views on what was shared with them by Dr Strain, below is copies of these notes 3 pages in fact, I have had to try and write them out below the image due to the poor quality, the last page I was unable to write due to such poor copy but place it here for the record.
Here is the first page
Here is my attempt to copy [see below in italics] the above note, however, the correctness cannot be guaranteed you will have to access such yourself BUT the first two lines as well as the last two lines is very clear, and damning.
Attention: Walton Van Winkle.
While the material perhaps has advantages over Lipiodol it also would appear definitely more dangerous to use – the clinical reports and the animal work undoubtedly ????? that something in the preparation is capable of setting up definite meningitis. The similarity of ????? symptoms to those suffered by patients injected with Winthrop’s Pyrogen – pontocaine combination raises the question as to whether they have taken any precautions to ?????? for ??????. Certainly any ????? for spinal injection, might to be pyrogen free, it is probable that Lipiodol doesn’t contain much in the way of pyrogens. Also the intense foreign body reaction around cysts of the material is disturbing. It would be interesting to know the temperature reactions after filtering this ????? a ???? filters. The second point I would like to raise is concerning the stability and identity of the material – they admit it is an unknown mixture but I would if physical constraints given are adequate to ensure uniformity of composition. In regards to stability there is nothing said other than that the material darken steadly to exposure to sunlight. Is any fine iodine liberated? If so, the material contributed in such disease and Hyperthyroidism – I assume they haven’t had time to answer the last paragraph of your letter dated Nov 9 1943. There so called assay is not very satisfactory seems about anything is allowable except death of the animal.
Signed W Fassett.
The second page follows as a graphic and below it, in print.
- Re. Acute toxicity of intrauterine injection, it is not very clear that any dose of the undulated or un-emulsified materia can be injected, while on the other hand the largest dose of the emulsified product was not fatal. It would be desirable to find what dose if any could be injected of the undiluted material if death is by embolism, it seems likely the undiluted could be treated radiographically, thus showing the toxicity to be due to the physical ????????? and not the inherent toxicity of the compound. The latter should be experienced further using the emulsified or solvent method of dilution. The data submitted gives only an indeterminate bit of information.
- Re. acute toxicity of oral administration to rats, sections were taken from only one animal. This does not seem ‘sufficient’ for a pathological study.
- I do not feel entirely satisfied with this study, although it is hard to give any good reason. I think that the toxicity characteristics were explained by them to see if the material was “safe enough” to use rather than “how safe is it”. The predicted absorption of 3 c.c. per year for man is not borne out by their report. They do not warn against intrauterine or intra pleural use. If they would clarify several ????? of this sort, it might be ok. The Radiologist who have reported, likes it, also the neurosurgeons too. [Initialled by NSL]
Page 3. [See below] You will have to screen this yourself I am unable to clearly read it, however, one section is ok, its in regards to their concern of possible ‘free iodine’ and should be tested for such, no evidence to date has been sourced by me that shows this was ever done!!!
It is clear by the contents of these 3 pages that they are very concerned about the danger of this substance, including the limited provided animal tests, as well as a possible issue with ‘free iodine’. This documented concern shown here, is overshadowed by the fact that unknown to the FDA and its regulators, Rochester University Dr Strain and Dr Warren are already testing it on unsuspecting patients, be it injured military of civilians and have been doing so for the past 2 years, in “selected” hospitals.
On the 9th of November William Burke Owner of Lafayette Pharmacal received a letter from Walton Van Winkle Jr M.D. Acting Chief of the Drug Division of the FDA informing him of the following. [See a copy of that letter below] …’We have your letter of November 2nd with which you have submitted additional data for your pending application under section 505 of the Federal Food, Drug and Cosmetic Act for the preparation *Pantopaque*. This material has been considered as an amendment to your application for this product, The unamended application was filed with the Administrator on July 23, 1943’… [my words copy of such posted earlier] …’and a notice postponing the effective date of the application was forwarded to you on September 13, 1943’… [TO BE ADDED]…’Pursuant to the provisions of regulation (c) of section 505 (b) of the Federal Food, Drug and cosmetic Act notice is hereby given that the application which was filled, and which was pending before the Administrator, is now considered as having been withdrawn and the amended application is considered as having been filed on November 4th 1943, the data on which the amendment was received by the Administrator of the Federal Security Agency. We have not concluded our study of the amended application and this letter is solely to inform you of the filing date. On completion of our study you will receive further comment from us. We call your attention to the third paragraph of our letter of August, [see above] suggesting that you prepare and submit to us a circular setting forth the indications, dosage and contra-indications for this product. We will be unable to complete our consideration of this application without such material’… . Signed Walton Van Winkle, Jr. M.D.
All is quiet until the 21st of January 1944, remember the Regulators concerns in November regarding their belief that this submitted substance was …‘definitely more dangerous to use’ than that which was currently on the market? Well in 32 days time the FDA approves the Licensing of Pantopaque, stating and I quote: …’This application is effective’… Interestingly, the Chief Drug Regulator is NO LONGER Dr Walton Van Winkle Jr. but now someone new, a R.P. Herwick, M.D. will comment on this when we arrive at the related correspondence dated 22nd February 1944, But lets return to the 21st of January 1944 and that letter. Within it this letter Walton Van Winkle asks Bill Burke owner of Lafayette Pharmacal a range of specific questions that go the heart of Pantopaque’s ‘safety’; was this reason his position as Chief on the Drug Division ended soon afterwards. One of the questions asked was this …’From the description of control procedures contained in this application, we are somewhat in doubt as to the extent of the test to be made on each batch of the drug’… …’In discussing the preparation of the active ingredient, we note that certain physical constraints are mentioned and that the drug is assayed biologically on dogs’… . [I ask the reader to remember this section for it plays a significant part in the area of safety of Pantopaque a year after the FDA approves Patopaque.] The FDA point out that they ‘Lafayette pharmacal do not …’exert any chemical control over the drug after you receive the raw material’… …’and such is assumed to be done by Eastman Kodak or Rochester University’… . [In fact, it will be another 34 years before any medically trained person will be on staff at Lafayette Pharmacal] The letter goes on to state …‘The clinical reports which have been submitted leave one with the impression that a rather large number of reactions of varying degrees of severity have been observed with the use of this material’… …’ However, on the basis of the reports contained in the application and without additional data, we hesitate to permit this application to be come effective on the basis of its safety for use. It is suggested that additional reports be obtained from some of the investigators mentioned in the application’… .
What is needed to be understood by those reading this, is, whilst this letter is dated January 1944 the FDA was playing catch-up, they in just a short time had become an independent entity due to the changes to the Food Drug and Cosmetic Act of 1938. For the first time, manufacturers were required to show that a [new] drug was safe before it could be marketed, as well as the contents written on the product label were not only true but accurate. However, not only were the “new” FDA Drug Division small, they had been interacting with the developers of Pantopaque prior to these changes, furthermore, those involved with the development of Pantopaque were very eminent people that were renowned in fact held illustrious position within the medical and academic area. Due to such, these 4 M.D.’s of the new Drug Division of the FDA being on a fast learning curve continued to rely on the ‘old way’ of doing things, which naturally played into the hands of the developers of Pantopaque. You can read a little about the ineffectual “new” role of the 4 staff members of the Drug Division, this link is a transcript of one of these 4 sharing ‘his oral history’ for the record for the FDA History Department. http://www.fda.gov/downloads/aboutfda/whatwedo/history/oralhistories/selectedoralhistorytranscripts/ucm264480.pdf%5B/embed%5D See page 3 onwards, to get an idea of how things were at the time Pantopaque application was being processed. If you read a little further on, you will come to a reference to the ‘Liar’s Club’ of the new FDA, an interesting read. Well back to this letter, whilst I am penning a lot of its contents its important to do so, for this period is crucial to the understanding of how this was allowed to destroy millions of lives throughout the world. Walton Van Winkle of the FDA ends this letter by saying …’In our opinion, the proposed circular setting forth the indications and method of administration of this product is not wholly satisfactory because of the severity of reactions observed, we feel considerable stress showed be laid upon the necessity for removing this material on completion of the radiological examination. It might be well for the label of the product to bear caution calling this fact to the physicians attention, the entire circular creates the impression that reactions are infrequent and are of a minor character. The reports which have been submitted do not confirm this impression. We suggest, therefore, that a more thorough discussion of the side effects and potential toxicity be given in the circular and that it be stressed that these reactions appear almost uniformly if the product is not removed following examination of the patient. It is also suggested that the circular state that the product is not intended for use in the bronchi or in the uterine cavity’… [Soon, Pantopaque would be used for such examinations, information and evidence of such further into this Blog] …’At the time you submit the additional data regarding controls and toxicity, you should also submit a draft of a proposed revised circular and labels’… . Here is that 2 page letter below.
I need share a little of the History of the FDA, at that time the FDA itself was a very small sub-section of the U.S. Department of Agriculture, in fact, initially in 1938, they only had 4 medically trained staff whom oversaw the Drug Division as you can see by reading the above link I referred to earlier. By reading this you can get a better understanding of how easy it was for Eastman Kodak, Rochester University and Lafayette Pharmacal to manipulate this ‘new’ Drug Division within the newly formed independent ‘FDA’. For until the new FDA ACT of 1938 the FDA had minimal legislative power and relied heavily on Heads of Departments at Hospitals and Universities for advice and direction, and sadly it seems they continued to do so with Pantopaque and throughout World War two, and like today, they are intertwined for advice not only from its Federal Government and powerful men in Congress but pharmaceutical companies as well. This reliance, clearly enabled Pantopaque to be promoted this way, as its very clear that end-users had no idea or interest in the safety of Pantopaque only in its ability to do its job, to outline the subarachnoid or brain. Its also important to taken on board how important this period was for another ‘new drug’ being introduced in the US again in 1941, this being Penicillin. It is my belief that with the support of the Rockefeller Foundation, an Australian by the name of Howard Florey [the developer of Penicillin from Oxford University Dyson Perrin Labs, yes same place Pantopaque copy was develop] did he exchanged the Penicillin formula for the Iophendylate Pantopaque formula, for he and his colleague Norman Heatley travelled to the United States in the summer of 1941.
Over this period running up to the FDA approval of Pantopaque 32 days later, a selection of letters (6.) from a “selection” of Military Hospitals mainly from Neurosurgeons.
I will place the first letter on here on the Blog, the other 5 by a PDF link afterwards.
As you can see all these supportive letters refer to using a dose of less than 3ml and aspirating, one writes about …’finding the same irritation as Lipiodol’… . However, whilst they refer to seeing NO adverse reaction whilst carrying out the myelogram, CIAA develops for most slowly, for others it develops through multiple Myelograms and multiple residual build-up of the non-removal part of that injected. The complex nature of CIAA is ‘an outcome of a dose that remains in the subarachnoid space that goes above 2.85 c.c’. © For those that have further myelograms to diagnose what to them is an unknown entity [CIAA] being experienced only increases the CIAA pain and disability.
For those reading this that had the copy of iophendylate Pantopaque known as either Myodil or anyone of the following chemical name depending on where you lived at the time of your Myelogram, they are …10-(4-Iodophényl)undécanoate d’éthyle [French] [ACD/IUPAC Name], 202-787-8 [EINECS], 4-Iodo-iota-methylbenzenedecanoic Acid Ethyl Ester, Benzenedecanoic acid, 4-iodo-iota-methyl-, ethyl ester [ACD/Index Name] , Ethyl 10-(4-iodophenyl)undecanoate [ACD/IUPAC Name], Ethyl-10-(4-iodphenyl)undecanoat [German] [ACD/IUPAC Name], Iofendilato [Spanish] [INN], Iofendylate [INN] [Wiki], Iofendylatum [Latin] [INN], Iophendylate, iophendylate, p-, [99-79-6], 10-(4-Iodo-phenyl)-undecanoic acid ethyl ester, 3-09-00-02627 [Beilstein] BENZENEDECANOIC ACID, 4-IODO-.IOTA.-METHYL-, ETHYL ESTER benzenedecanoic acid, 4-iodo-i-methyl-, ethyl ester, Ethiodan, Ethyl 10-(p-iodophenyl)hendecanoate, Ethyl 10-(p-iodophenyl)undecanoate, Ethyl 10-(p-iodophenyl)undecylate, Ethyl iodophenylundecylate, ethyl10-(4-iodophenyl)undecanoate, Iophendylate, p Iofendylate, JOFENDYLATE, Jofendylatum, MFCD00867941 [MDL number], Mulsopaque, Myodil, Myodyl, Neurotrast, PANTOPAQUE, Undecanoic acid, 10-(p-iodophenyl)- ethyl ester.
FIND LETTER OF L/P 15th Feb 1944
Lets move on, on the 22nd of February 1944 [see copy of this letter below] William [Bill] Burke Owner of Lafayette Pharmacal receives a letter from the FDA but NOT from Walton Van Winkle Jr. M.D. Chief of the Drug Division of the FDA, but from a R.P. Herwick M.D. who now holds that position notifying them that their application for a General Marketing License for Pantopaque was …’effective’…
The question that needs to be answered is why was Walton Van Winkle relieved of his position as Chief of the newly formed Drug Division of the FDA, at that precise moment? Was it due to the letter he’d sent as Chief of the FDA Drug Division only 32 days earlier, demanding a range of specific answers including evidence that Pantopaque was not dangerous, something he had stated ‘was so’, less than a year earlier. What influence was brought to bear on the FDA to “get rid” of Winkle and have him replaced with Herwick???
This letter goes on to state …’with respect to the use of this drug only under the conditions prescribed, recommended and suggested in the application. Should you decide to alter the composition, or dosage, or method or duration of administration or application, or other condition or use, an appropriative amendment to the application should be submitted for consideration’… …’Your attention is directed to section 301 (1), which prohibits the use in the labelling or in any advertising of any statement to the effect that an application with respect to this drug is affective under section 505 or that the drug complies with the provision of that section’… …’Section 505 (e) of the Act provides for the suspension of the affectiviness of an application if further experience and tests with the article show it to be unsafe for use or if it is found that the application contains any untrue statement of a material fact’… .
On the 17th of March 1944 the FDA receives a supportive letter [see below] regarding Pantopaque from the Mayo Clinic in Rochester [just up the road from Rochester University, the developers and 50% Patent holder of Pantopaque] the writer of this letter states the following …’In no instance has there developed a toxic reaction from the use of the drug. Furthermore, we find that the drug Pantopaque is exceedingly useful substance for localizing lesions in the subarachnoid space. It has not been proved too effective when the oil has had to br mobilized into the thoracic or cervical regions, since there is a tendency for the oil to break into droplets’… Here is that letter.
The following letter below is a letter from the FDA to the Mayo Hospital from yep, its Walton Van Winkle, HE’S BACK this is rather mysterious, ‘did he refuse to approve Pantopaque due to its know too toxic nature and dangerous’? So Herwick did it, this is something that needs answering, but trying to obtain such answers from the FDA will be very difficult. I have obtained two book links that cover such changes to the new FDA Act of 1938 and the involvement of Walton Van Winkle and Robert Herwick which clearly cover the Drug Division requirement changes once FDA Act 1938 was enacted. This clarify many of the issues I have raised.
This piece was taken from the book above, its an interesting read:
…’If a drug killed one person in 10,000 was of only minor use therapeutically it might be judged to be unsafe, whereas the drug which killed one person in a thousand if it had a marked and undisputed therapeutic value, such as the drug under question, it would still be a safe and valuable drug’… . This was taken from page 83. Its reference is : [J.J. Durrett, Memorandum of Interview with Perrin H. Long and E Kennerly Marshall [John Hopkins]. December 5, 1938, 88 – 69A-2099 NDA 90, vol 1, W-NRC and Walton Van Winkle Jr. to Paul Dunbar and Robert Herwick, January 30, 1946, 88-59A-2736, Box 220, F 505, 1074-509, W-NRC.]
Another similar book that writes about the FDA development and life between 1900 and 1990 this is also an interesting read if you want to understand how all this was allowed to happen.
You of course if you so wish, can visit the FDA website itself to “access” the FDA History, but its very selective, if you know what I mean.
1700 application was filed with the FDA during the first 18 months of the 1938 Act.
On the first of April 1944 Walton Van Winkle Jr wrote to the Mayo Clinic to a Dr A.W. Adson whom sent him the supportive letter seen above dated 17th of March 1944. Dr Winkle thanked him for his letter regarding his …’observations on the new drug Pantopaque. The information which you have furnished us has been quite helpful and we appreciate your kind cooperation’… . What is interesting, Dr Adson is a Neurologist, from the Department of Neurology, and not from the Neurosurgery or Radiological Department of the Clinic.
The letter below dated the 18th of April 1944 was sent from the original owner of Lafayette Pharmacal William Burke 8 weeks after Pantopaque was “approved” by the FDA, to the FDA. This letter was to inform them that there was a change in Pantopaque ‘Statement of Directions’, and informed them that a printed statement of Directions will be sent to them with the [related] labels when they are completed. This ‘change’ 8 weeks after it was approved, begs the question how and when were the NEW Safety/Toxicity data obtained by the FDA, for there are no trace of such. The next obtained letter explains the reason for the change, however, I am unable to understand what it means or its ‘effect’ on the original chemical formula. [See second letter] dated 18th of May 1944 further below.
On 16th of May 1944 Dr William Strain wrote the letter seen below to Dr Walton Van Winkle Jr of the FDA informing them that he on behalf of the University of Rochester that the preparation known as Pantopaque for which NDA 5319 was filed with you by the Lafayette Pharmacal Inc., are in error. He goes on to say that as University of Rochester School of Medicine and Dentistry was supervising the preparation for the time being, he was writing to them, the FDA to correct the error. He informs the FDA that there is an error on page 2 of the Provisional Specifications (being the revision dated the [5th of Feb 44] showing the refractive index at 20° (nd20) is 1.5200-1.5242. This should read 1.5200-1.5280. This error arose through confusion in the temperature: the value 1.5242 is a limiting value at 23° C., rather than at 20° C. He closes of the letter by saying ‘we trust that this note will be adequate notification, and should you wish a more formal statement, will you recommend a procedure that we should follow’. Here is that letter below.
20 weeks later on the 4th of November 1944 [see copy of the letter below] Dr William Strain wrote again a letter to Dr Walton van Winkle of the FDA requesting that the ‘ongoing testing’ of purity of Pantopaque be STOPPED, stating that currently each ‘new’ batch of Pantopaque is tested on dogs byway of an intrathecal injection, and he believes that such is no longer warranted. He believed that such a procedure could be dropped, and the reliance of Pantopaque purity be solely by means of the physical and chemical constants only. Finishing the letter by informing the FDA that he would be in Washington …’sometime time after November 15th’… and would like to discuss such with them. The reason for this request to stop testing these dogs for the purity of Pantopaque, is due to the “misleading” temperature spike after the dogs are injected with Nembutal the anesthetizing agent [see Strains letter below, dated 12th October 1945 to William Bucke Owner of Lafayette Pharmacal] Bucke as requested by Strain relays such in writing to the FDA the following month, BUT not to Dr Walton Van Winkle Jr, of the FDA but to a Dr Herwick of the FDA, now cast you mind back, wasn’t it a Dr Herwick that “approved” the NDA [New Drug Application] for Pantopaque and NOT Dr Winkle Jr.]
Again if you dig deep enough its amazing what you discover after the fact. In fact, 71 years later. Now how will I word this so the importance of what I am about to share, resinates with you the reader. Well, before the developers lied to the FDA regarding the safety of Pantopaque when they applied for its General Marketing License, [GML] they also mislead the Radiological Profession of the ‘safe dose’ remember? Soon after they obtained the general marketing license for Pantopaque, they then notified the FDA of the “need” to change the refractive index due to a previous error prior to obtaining the GML, it is my belief that they did this to throw off the next change being the purity of Pantopaque referred to above. The reason given to change this process of injecting dogs was in the opinion of Strain that the Nembutal anaesthesia was causing the rectal temperature of the dogs to increase, however, in June 1944 five months earlier Strain’s C0-worker Stafford Warren wrote the complete opposite in a Medical Journal article where Warren writes as the FIRST of 9 conclusions [last page] regarding temp spike in dogs …’Nembutal anaesthesia results in a generalized parallel FALL in the subcutaneous, intramuscular, and rectal temperatures of the dog’… Further lies!!!
Decided to place the first page here, then below it the full copy of the MJA by PDF
It is quite clear, this explanation was to throw off the FDA regarding the [hidden] too toxic nature of Pantopaque. So, lets take a close look at these letters to understand how Strain did this, I need to jump forward for a moment, [we will come back] to the 12th of October 1945, (see below) Dr Strain writes to William Burke owner of Lafayette Pharmacal and the manufacturer of Pantopaque and informs him that they are stopping the testing of Pantopaque byway of injecting dogs with Pantopaque and recording the rectal temperatures taken before and after the procedure. He goes on to state that …’we have felt that the intrathecal assay was valueless’… [in Dogs] …’and it now has been found that the production of fever or slight temperature elevation appears to be due to the Nebutal rather than to the intrathecal injection of ethy iodophenylundecylate’… [being Pantopaque]. He also informs him that NO search of the literature has revealed any studies on the delayed effects of Nembutal on rectal temperature of experimental animals, however as we known, 16 months earlier Dr Strain Co-worker Dr Stafford Warren penned such an medical journal article [Posted above. So a further lie to the FDA] where he stated that there were a FALL found of temperature and/or fevers after injection. Here below is the letter from Dr Strain to William Bucke of Lafayette Pharmacal informing him of those changes mentioned above, stating …’to accomplish the proposed changes we are inclosing permanent specifications for ethyl iodophenylundecylate (Pantopaque) revised as of August 15th 1945’… . Here is that 2 page Letter, below.
After receiving Dr Strains letter above, Burke writes once again to the FDA to [as I mentioned earlier] Dr Herwick whom issued Pantopaque’s General Marketing License, Mr Burke, repeat what Dr Strain shared with him, and relayed such to the FDA under a amended NDA 5319, [see copy of letter further below dated November 12th 1945] he also states that …’The University of Rochester was responsible in a large measure for the development of the medium’… . He goes on to make mention of the fact that Dr Strain, in ‘his opinion’ believes that intrathecal assay in dogs is a meaningless procedure. He further makes mention of the data supplied to Dr Winkle by Dr Strain of …’the intrathecal assay measures the delayed effect of Nembutal anesthesia rather than of the contrast medium under test.’… . This removal ‘removes’ the ability of testing for purity of the medium and the only check is …’physical constants and chemical analysis’...
BUT what does that mean?
One needs to re-read Sharp’s Deposition posted earlier to clarify this, they not only removed the purity test on Pantopaque but do not warn physicians by NOT entering Pantopaque in the Physician Desk Reference Manual, so physicians had no knowledge of the risk of their patient having a Myelogram with Pantopaque, which is now not being checked for purity. For within the Physician Desk Reference manual it also lists not only the names of Drugs but their related Product Inserts, something that Physicians could share with their patients prior to any exposure.
Below is William Burke letter to Dr Herwick FDA providing the FDA with the new amended Specifications for Ethyl-iodophenylundecylate and details as to why these changes “were needed”.
However as I said, I would come back to 1944 for its important that I try and keep this in order date wise, but not easy. On the 5th of May 1944 as you recall Lafayette Pharmacal applied to the FDA for a NDA [new drug application] for Pantopaque, this [NDA] became one of 5 patented on the 9th of October 1945 by William H. Strain Rochester N.Y, John T. Plati, Passale N.J. and Stafford L Warren Oak Ridge, Tenn., and Eastman Kodak Patented 5 claims (CI. 260— 476) this Patent was numbered 2,386,640. However, as you will remember the FDA refused the initial NDA finding Pantopaque to be ‘TOO TOXIC’, the dates seem to be a bit confusing here, for on the 15th of May of the same year  being 10 days later, the Dyson Perrins Laboratory at Oxford University England submitted a MJA to the Bulletin of the Society of Chemistry titled The Preparation of Iodine-containing x-ray contrast substances IV. Ethyl-iodophenylundecoate (“Pantopaque”) here are those to articles, first a copy of the UK MJA, and second the US Patent and below them both as a PDF.
Here is a Medical Journal Article dated December 1945 Titled Pantopaque Meningitis Disclosed at Operation, this article was published only weeks after Iophendylate Pantopaque was not only Patented, but approved by the FDA for General Marketing, as deemed to be safe. This article must be seen as the first RED FLAG implicating Pantopaque as a substance that caused [quote] …’a rather pronounced inflammatory response which was found among the nerve roots of the cauda equine at operation sixty hours after 3 c.c. of pantopaque had been introduced intrathecally’… [In the Conclusion of this article the following damning remarks seem to have also gone unheeded] …’From the present case reported and from a survey of the literature there is no doubt that an inflammatory and proliferative meningeal reaction may follow the intrathecal introduction of pantopaque. Its use should be restricted therefore to those cases in which critical information is urgently needed for diagnosis and treatment. When employed, it should be injected immediately before fluoroscopy is done and it should be removed immediately after the myelography’… .
Here is the front page of this MJA and the full copy by PDF below it.
The last letter I posted above was dated 4th November 1944, the next letter I was able to access was dated the January 17th 1951 [see a copy below] where a Radiologist by the name of C. Edger Virden M.D. writes to Lafayette Pharmacy, yes, no mistake, he called Lafayette Pharmacal Lafayette Pharmacy making reference to …’relatively severe arachnoiditis’… being experienced, and asks if ...’there has been any change in formula or preparation or if anyone else has reported any similar reactions’… . To date I have been unable to find any response by Lafayette Pharmacal to Doctor Edger Virden, whom was later to become the President of the Radiological Society of North America. 
Here is that Letter.
As you can see the period when Pantopaque entered the general market and throughout the late 1940s a collection of Medical Journal Articles referred earlier were published by Military Hospital penned as I said by the same Radiologists or Neurosurgeons whom received those samples. Within these MJAs [which you read earlier] the authors praised the quality of Pantopaque stating it provided clear and sharp x-rays, limited information was given regarding patient welfare, other than a passing mention of patient seems to handle the procedure well. Furthermore, no follow up of these patients at any of these hospitals took place, but remember there was a world war on and due to such this didn’t enter into their minds considering the enormous amount of war injuries being experienced by these hospitals, this was to the advantage of Kodak and Lafayette Pharmacal for on checking no related information was shared with the FDA.
Before, I continue I wish to acknowledge Dr Sarah’s work published in 2002 where some of the information shared here was taken, mostly, regarding references to MJA’s, whilst much was a shared production ‘evidence wise‘ between us both it would be wrong not to mention such here, Thanks Sarah.
Let us continue.
If you cast you mind back to earlier in the piece, remember over the period that Lafayette Pharmacal applied for a NDA the FDA had only really just come together as a independent entity and had only a few staff members with limited knowledge and it is reported that they relied on the Manufacturers and their specialists to oversee their product safety, which played into the hands of those involved in the Pantopaque fraud. Furthermore, FDA having a backlog of 1700 new drug applications at that time did help, in fact NO further documentation was sent to the FDA for many years, after Kodak through Lafayette Pharmacal gain Pantopaque Marketing License. However, Kodak was becoming more more worried about the series of complaints about Pantopaque being received so Mees from Kodak writes to the Owner of Lafayette Pharmacal William Bucke to the effect that he was assigning responsibility to Lafayette Paharmacal regarding Pantopaque, thereby placing Kodak at a legal distance from the Pharmaceutical Company. The Pantopaque label whilst in 1944 recommended 2.5cc things have changed now in the 1950s the label includes information on the use of 30cc whilst at that time the dose being administered have increased [without FDA approval] to 6 – 9 cc however, what was missing of this 1950s Product Insert was a warning of the serious side effects of Pantopaque as reported by Van Winkle. These serious side effects were further reported in a 1951 MJA by Luce where he describes patients developing meningitis due to a sensitivity to Pantopaque. Soon Erickson and others continued to warning of serious adverse reactions to Pantopaque including a fatality after a Pantopaque myelography due to obstructive hydrocephalus, you can find this in Erickson’s 1952 MJA titled: ‘Late Meningeal Reaction to Pantopaque used in Myelography’ initially with the front page below then the full MJA as a PDF.
Full MJA as a PDF.
Report of a Case That Terminated Fatally.
Others were also reporting increasing problems with Pantopaque, Scurr for instance with others in 1953 described meningeal irritation due to Pantopaque, the question I am sure you are asking yourself is, where was the FDA in all this, our ‘Gatekeeper’, put there to protect us all, however, due to the non-requirement of end-users of Pantopaque to report such reactions to the FDA, the FDA was unaware especially as a specific FDA Inspector was in the pocket of Bucke at Lafayette Pharmacal, being a personal friend and golf partner etc, I will write further about this and provided related evidence in due course. In 1954 other authors of MJAs such as Hurteau referred to the development of Arachnoiditis after using iodised oil in myelography stating ‘clinical and laboratory data …’suggest that Pantopaque may contribute to, or possible cause sever reaction within the subarachnoid space’…, and went on to reinforce the need to remove as much as possible of the oily dye as soon as the Myelogram was finished.
Full MJA as a PDF.
Due to this growth of reactions to the use of Pantopaque being seen throughout America and elsewhere in the World two Doctors by the name of Meacham and Capps decided to write a paper Titled: Pantopaque Myelography: The Meningeal Responses to Retained Pantopaque in the Experimental Animal.
Still looking for the MJA its here somewhere will post asap
In regards to their findings they stated that Pantopaque if left in the body …’remains [a] serious and at times fatal complication’… . They went on to state …’there is, therefore, virtual unanimity of opinion here in America that the oil used for myelography should be removed as [none] traumatic as possible immediately after the procedure’… . Reader, if you go to the Summary and Conclusion of this MJA you will find the following …’The retention of Pantopaque in the spinal subarachnoid space of the dog consistently is productive of an extensive, acute meningeal response to the oil’… .
I am covering this period in some detail due to the importance of it, as you can gather Pantopaque was too toxic for human use, however, as I have shared with you earlier Kodak and Rochester University as well as Lafayette Pharmacal manipulated their new drug application for Pantopaque with the FDA. The information I have shared with you since that “successful” 1944 NDA clearly shows that not only was Pantopaque far too toxic for human use, but the evidence of such misleading facts found in many MJAs publish since, supports such. In 1956 a very important MJA was published by F.L. Davis in Lancet the article was titled: ‘Effect of unabsorbed radiographic contrast media on the central nervous system’. Where you will see he reports that 124 patients at surgery up to a year AFTER myelography. 60% showed immediate reaction and 12% developed “chronic adhesive meningitis”; Davis also reported that in this study 3% incidence of severe chronic arachnoiditis.
As this only a two page MJA [although specific in data] I decided to post it as is, below.
For those reading this in Australia , I am sure you will not only find the following MJA not only very interesting but disturbing, for in Australia like in many of the 107 countries where Iophendylate was used. In this Australian MJA Titled: Complications of Myelography published on the 10th of November 1956 the author Davis pen the follow …’the injection of ethyl Iodophenylundecylate is not without danger’…[further into the article, Davis goes on to pen the following] …’Davies supplied the answer, in part at least, when he points out that the large amounts of medium shown by radiography to be present in the cranium many years after injection indicate a slow rate of absorption’… [This flies in face of what the developers told the FDA] Davis goes on to say, …’This emphasizes the desirability of removing as much of the contrast medium as possible after myelography or at operation’… …’A more satisfactory solution, of course, would be the development of a completely innocuous contrast medium’… .
I truely believe that ALL end-users be it the Radiological Profession, the Neurosurgeons etc should be held accountable for leaving this highly toxic substance in patients bodies, especially since the Developers, the FDA and ALL MJA’s Product Inserts stated that this “dye” MUST be removed at the end of the Myelogram, oh, so I report this correctly, Glaxo UK who copied this Kodak “dye” did NOT use the word ‘must remove’ in their Product Inserts until early 70s their wording prior was ‘may’ remove, which flies againest the products instruction of usage.
Again, this is only a two page MJA so I will post it in full below.
The following year a MJA Published in Radiology raise the question of “what is Toxicity?” it was penned by Peter K. Knoefel M.D. Titled: The Nature of the Toxic Action of Radiopaque Agents. He raises a interesting fact, which although i have over 1500 MJA this is the only one that states the following …‘All people are more sensitive than all rats, but show the same frequency distribution of sensitivity’… . He then in his conclusion states the following which again was ignored …’it may be said that the nature of the toxic action of radiopaque diagnostic agents is not understood and requires investigation’… .
As its only two pages I will post it here in full.
An interesting MJA I came across showed that whilst there were concerns regarding this “dye” on many fronts they not only kept on using it, but also continued to increase the dose used. The MJA I am referring to was published a year after the hightened concern on its toxicity and dangers to patients, its Title: Large Volume Myelography found in the Annuals of the New York Academy of Sciences 1959, the two authors were Eugene G. Tainter, Charles E. Grayson. [See below] when you read this MJA you will be concerned on some of the comments given, such as …’technical deviations due to errors in needle placement, while professionally embarrassing, produced no untoward clinical effects, immediately or later’… And whilst the authors make mention of such incorrect needle placement into the intradural area (see figure 7a &b) traveling along the dural and the nerve sheaths. Also there was mention of it being seen …’seen in the small pulmonary aeterioles in the base of the lungs’… . The MJA’s Summary is very interesting, the authors make mention of the fact …’the one drawback to this medium [dye] is its lack of rapid adsorption from tissues and spinal fluid’… . They finish off their Summary by stating the following …’The Medicolegal implications of residual dye are frightening’… Finally, they refer to the dangers of patients with …’residual of this dye preclude the use of radioactive-iodine tracer studies for the lifetime of the patient’… . Something I am sure they do not tell the patient, they didnt tell me, when years later I had a radioactive-iodine tracer study done. Please note the following, [last paragraph] …’A new radiopaque agent for myelography is urgently needed. It should have all of the excellent qualities of Pantopaque and, in addition, must be absorbed from they spinal fluid from body tissues at a rapid rate’… . Its very clear that even in 1959 end-users were very much aware that Pantopaque DID NOT absorb as promoted by the developer and manafacturer, and in fact, like Lipiodol it led to [Chemically Induced] Adhesive Arachnoiditis but unlike Lipiodol where they stopped using it on patients due to the harm it was doing, they did NOT do likewise with Pantopaque. In fact, compounding this use 75% to 85% of patients had it then left in their body in most of the 107 Countries it was sold.
Here is the full MJA HereHere is the full MJA as a PDF.
Interestenly, but NOT surprisingly a similar Article was published in the Journal of Radiology titled: ‘Upright Large Volume Dynamic Myelography’ by Kvernland, Grewe, Woolley and Lee. Vol 72 pages 562 – 568. So, what you can see here is one MJA published for Neurosurgeons and another ‘this one for Radiologist I have place a copy of that article below first just the front page and then below it a full copy as a PDF file.
Here below is a full copy as a PDF file.
Soon On the 1st of January 1960 Lafayette Pharmacal produced a Product Insert for ‘Large Volume Pantopaque Myelography’ to date I have been unable to find any application to the FDA for such increase being to 12 cc, or for that fact any FDA related toxicological data on such dose on humans. However, within this Product Insert it refers to …’As many as 40 cubic centimetres of Pantopaque have been slowly injected without the removal of spinal fluid with no untoward reaction’… . Please see a copy of this 1960 Product Insert [PI] below.
Place your cursor key on image above as it is difficult to read like this, and click it will take it to a new page where you will be able to read it.
A FULL set of Product Inserts of the life of this “dye” are available, which shows how ALL developers manipulated the words including removing them ‘later’ after the FDA instructed them to add changes, they complied and submitted new PI and after a little while removed ‘said’ warnings.
ADD the full collection of Pantopaque Product Inserts here.
Throughout the 1960s the scale of deception practised by the Lafayette Pharmacal escalated. Studies performed by Hazleton Laboratories in 1962 looked at intraperitoneal and intramuscular injections of Pantopaque. These showed infiltration of the compound beyond the injection area as well as inflammation and calcification, and was never licensed. In the same year two Doctors by the names of Mason and Raaf wrote a MJA titled: Complications of Pantopaque myelography Case report and review they reported a case of obliteration of the subarachnoid space by Pantopaque arachnoiditis, here is that article first the front page and then the full MJA as a PDF.
Full MJA PDF file below.
Also in 1962 one year before JFK was assassinated he established the Kefauver-Harris Drug Amendments, which required manufacturers to prove to the FDA that their product was both safe and effective prior to marketing. In addition the FDA gained control over advertising.
Here is JFK signing the Amendments into law.
The following year JFK would be dead.
What seems to have been an ‘ongoing’ ploy of not only Developers but those that write “specific” MJAs to report possible causes to adverse reaction by patients to Iophendylate Pantopaque & Myodil etc such as talcum powder used in surgical gloves and blood etc in sodoing ‘it muddies the water’ deflecting the true cause of such from this “dye”. As more and more end-users were not only becoming very worried regarding ‘using Pantopaque’ that some decided to pen MJA’s regarding such, one such MJA was that of Howard and Curry  titled: Pantopaque Arachnoiditis: Experimental Study of Blood as a Potentiating Agent. [See below]Within this MJA they published the outcome of their dog study where they looked at blood as a possible cause of the damage found. Their findings were that …’Pantopaque alone caused a chronic inflammatory response’… . Furthermore, they found reactive changes around encysted oil droplets. They also found that areas of inflammatory was greater when blood was present, however, this was also found in the cervical region and at the base of the dogs brain, all were directly associated to the presence of Pantopaque. Dogs used in this study were injected mainly in the neck area, furthermore, Pantopaque was left in due to the difficulty of removal, and in fact, its impossible to do so with dogs.
Here is a full copy of this MJA as a PDF.
Another MJA that raised further awareness of the dangers of ‘oil based’ contrast mediums [dyes] which was published again in 1963 was in the Journal of Neurosurgery one of the most Prestige MJA being published at that time. In fact, it was for Neurosurgeons those that either carried out the Myelogram or ‘ordered’ such through Neuroradiologists, here you can see this MJA is in two parts the first regarding Lipiodol and then Pantopaque. This specific MJA shared with the reader important facts regarding initially the first dye developed which I mentioned earlier, being Lipiodol. This oil dye was developed in 1901 by Marcel Guerbet and Laurent Lafay and entered the market place in 1921 and ceased being used 9 years later in 1930 due to it causing [Chemically Induced] Adhesive Arachnoiditis. Sicard and Forestier wrote this part of the MJA now recognised as one of the Classic’s it was Titled: General Method of Radiological Exploration by Iodized Oil (Lipiodol). What is disturbing is how they promote not only Lipiodol from an end-users point of view but disregard not only ‘how such would harm patients‘ but the dose used which by increasing [without FDA approval] led finally to [Chemically Induced] Adhesive Arachnoiditis. Likewise this happened with Iophendylate Pantopaque the end result being once again [Chemically Induced] Adhesive Arachnoiditis was due to two specific issues it was always ‘too toxic’ and the fact the end-users continued to increase the dose they used believing it was safe because of the information being provided to them by the developers. Sadly unlike the developers and end-users of Lipiodol who once realised it was too toxic and very harmful to patients stopped using it, Pantopaque end-users did not, they kept not only the FDA in the dark but the end-users for the next 25 years BUT patients. The second part of this Classical MJA was Titled: Iodinated Organic Compounds as Contrast Media for Radiographic Diagnoses III. Experimental and Clinical Myelography with Ethyl Iodophenylundecylate (Pantopaque) I will let you read it [a must] but I would like to record here what the authors wrote at the end of this article in its Summary …’Ethyl iodophenylundecylate (Pantopaque), a new contrast medium for myelography, is more fluid and is thereefore more easily injected and removed than previously described oil-type contrast media’… [Referring to Lipiodol] …’In addition to these physical advantages, the medium IS ABSORBED from the subarachnoid space with relative rapidity’… . [I the writer placed the Capitals] In fact, both oil based dyes do NOT absorb, the just lose their opaqueness, leading to a belief its gone, and any risk of being sued.
Here is a full copy of the MJA as a PDF.
In September 1962 Lafayette Pharmacal submitted a revised ‘Statement of Direction’ for Pantopaque the first since the original Statement of Direction was submitted on the 10th of February 1944. Here is a copy of that revised ‘Statement of Directions’ for Pantopaque it has 4 pages so I decided to post them all here. What is critical for the reader is how the wording has been structured to mislead end-users and endanger the patients. Overtime I will post later Product Inserts and I suggest you copy and print them out to highlight the changes, for they are very pertinent to how Eastman Kodak and Lafayette were able to mislead everyone, except the FDA whom as our ‘gatekeepers’ were MIA.
Here below is the 1944 Product Insert that was released first, and below it the changes seen in the 1962 PI.
The following year 1963 [see below] Lafayette Pharmacal submitted Form 161, which was an IND exemption for human trials this was approved by the FDA.
PLACE COPY HERE
In 1964 Dr. Hagan of the Division of Toxicological Evaluation a Branch of the FDA decided to review the animal toxicity data for Pantopaque [remember KODAK and Co, did NOT submit the damning data found regarding the too toxic nature of this substance,] but this was withheld from the FDA. However, even what they had submitted as part of their original NDA 5-319 on checking raise concerns so much so, that Hagan suggested that they repeat the data provided to them to ensure this substance was in fact ‘safe’, especially regarding its pyrogenicity, misteriously this was NEVER DONE.
Between 1964 and 1969 a collection of medical journal articles were published concerning adverse effects of Pantopaque [USA/WW] and Myodil [GB/WW] whilst there are many held in my library, in fact 1500+ I will mention a few. Fisher’s MJA  found in Radiology titled: An experimental evaluation of Pantopaque and other recently developed Myelographic contrast media. Fisher’s study was on cats and he came to the following conclusion …’mild inflammation in all animals’… …’was poorly absorbed and was more irritating as an emulsion’…
Here is a full copy of the MJA above
This was also found 30 years earlier prior to Pantopaque obtaining its NDA approval, [CRITICAL] please remember they NEVER submitted these specific emulsion test data to the FDA.] Fisher belived that the cause of such irritation was due to reduced particle size of Pantopaque after being injected thereby increasing the area of exposure and thus the meningeal reaction.
Also in 1965 Maupin, Baker and Kerr penned a MJA that was published in Radiology its title: Emulsified Pantopaque, Its possible application in Myelography, where they stated that when they injected Pantopaque into the cistern of dogs they found that the emulsified Pantopaque caused severe reaction obliterating the subarachnoid space and caused dense matting of the spinal roots.
Here is a copy of that MJA
I will place below a list of MJA published between 1963 and 1966 as a PDF file if any of these MJA’s are required to be further investigated by you the reader please let me know and I will forward you a copy.
Whilst the world continues to believe this too toxic substance is fine and ‘doing no harm’ end-users were finding that this “dye” when drops end up on the floor, it ‘ate the tiles’ away. What is sad, minimal reaction took place within the medical arena here is a MJA where such was raised.
Not only was Eastman Kodak and their cohorts becoming concerned so were end-users which created a flurry of MJA’s being published not only raising concerns of the growing problems being seen by them when using Pantopaque, but some documenting Animal studies carried out by themselves to challenge the data being promoted by the Developers. So much so, that I have decided to list a collection of some of these available Published Animal Studies by those other than Eastman Kodak and Co. My reason in doing so, is due to the limited availability to the General Public today of MJA’s due to Medical libraries stoping the general public using them, yes you can buy them [$30+ a pop] but first you need to research and that’s kind of difficult if you cant use the Library in the first place, another way to stop you finding out the truth.
Interestingly, one of the developers of Pantopaque whom was promoting the ‘absorption’ of this “x-ray dye” over the next decade also published a MJA less than one year after Pantopaque was awarded its General Marketing License saying the opposite. The MJA was Titled Iodinated Organic Compounds as Contrast Media for Radiographic Diagnoses: V. Escape of Pantopaque from intercranial Subarachnoid Space of Dogs. this MJA can be found in Radiology year 1945 pages 47 – 50 it was penned by Strain, French and Jones.
To save you time and money here is initial the front page of the MJA, and below It, a full copy as a PDF File.
PDF MJA [copy to be added]
Another MJA that needs mentioning was published in 1954 by Hurteau, Baird and Sinclair which can be found in the Journal of Bone and Joint Surgery Titled: Arachnoiditis following the use of Iodized Oil. whilst I will place a full copy below its important that I share the MJA’s Summary…’Clinical and Laboratory data presented suggest that Pantopaque may contribute to, or possible cause severe reaction within the subarachnoid space. Verbal communication indicating similar experience and a more conservative in their use than is often practised. The importance of complete removal of Pantopaque is evident’… .among Neurosurgeons has suggested to us that there is a need for more critical ???? properties of Pantopaque Due to this increasing concern about the ‘safety’ of Pantopaque by end-users, not only in America but worldwide Kodak in cohort with Lafayette Pharmacal decided to develop ‘another’ Pantopaque that stood up to the approaching re-scrutiny of the FDA approved Pantopaque currently on the market. So to reflect the growing “rumblings” Kodak and Lafayette Pharmacal submitted a supplemental Application to their NDA 5319 Pantopaque product, to produce Pantopaque II containing 15% organically bound iodine, half of that of Pantopaque I being sold on the world market and throughout America. It is important to inform you the reader that Pantopaque I. was the ONLY x-ray dye being sold throughout America and the World and this continued until 1978 in all, 42 years other than some Scandinavian countries where ‘water based x-ray dye was used, but this required the patient to be anaesthetised, and time is money.
Here is a copy of the 1954 MJA by Hurteau, Baird and Sinclair Titled: Journal of Bone and Joint Surgery Titled: Arachnoiditis following the use of Iodized Oil as a PDF file.
place a copy of the PDF MJA
On the 26th of January 1966 Lafayette Pharmacal attorney a Bradshaw Mintener wrote to a Mr. J. Hauser, of the FDA, Bureau of Medicine, regarding IND#1-161 submitted by his client. He stated that Lafayette Pharmacal had previously filed a IND#1-161 on June 6, 1963 to market Pantopaque with 15% iodine. He referenced the NDA that had initially been approved for Pantopaque (30%) in 1944, the comparison of the new Pantopaque product, and informed the FDA that his client now wishes to now withdraw IND1-161 and submit the marketing application as a supplement to NDA5-319. The reason given by Lafayette Pharmacal legal representative was …’in the course of years, because of the trend toward using greater volumes (* bold and italics added for emphasis) of Pantopaque, and because the great density even within the usual amounts of Pantopaque 30% may obscure the more subtle shades of the spectrum of density which one uses to detect the presence of compressive lesions involving the subarachnoid space, many neurosurgeons and radiologists have requested a less dense material’… . [Suzanne Parisian, M.D. 2002] He also informed the FDA that the Company will in due course provide supplemental information to the Department as well as reports of related clinical studies on Pantopaque II. Furthermore, he stated …‘in view of the fact that the 15% product is the same as the 30%, save for the iodinization producing a product with less iodine content, Lafayette Pharmacal would like to submit this supplemental application to their NDA 5319 and recall their IND application 1161, if this is necessary . Also Pantopaque II will be distributed by seven major x-ray companies as well as Lafayette Pharmacal, Inc. and enclosed you will find labeling for all distributors. The study performed at the Neurological Institute was exhibited in the scientific section of the American Neurological Association Meeting, held June 14-16, 1965 in Atlantic City’… .[Suzanne Parisian, M.D. 2002]
On March 17, 1966 Mr. W, S, Bucke, President of Lafayette Pharmacal, Inc. wrote a letter to Dr. Frances O. Kelsey, Chief of Investigational Drug Branch, Division of New Drugs regarding the status of IND 1161: …’Thank you very much for the courtesies extended during my recent visit to your office and this will confirm our discussion relative to your letter of February 17, 1966. The error in the IND number occurred in the office of Mr. Bradshaw Mintener in his letter of January 26, 1966 addressed to Mr. Julius Hauser’… He went on to write …’Referring to paragraph #3 of your letter of February 17, 1966, we do not wish to discontinue our study under Exemption (IND 1161), our reason being that on the suggestion of Mr. Julius Hauser, Bureau of Medicine, we have filed a supplemental application. This was filed by us by Mr. Bradshaw Mintener and we are awaiting your opinion on this supplemental application’… It seems that the FDA did not accept the proposal of Lafayette to submit Pantopaque II as a supplement to NDA 5-319 and withdraw IND 1161 for obtaining clinical data for inclusion in a new NDA. Dr. Kelsey and her staff had determined that FDA’s marketing approval of Pantopaque II was to require the submission of a separate new NDA to FDA by Lafayette Pharmacal.
By this time I am sure Bucke and Co of Lafayette Pharmacal are becoming very concerned about having to do so, due to what they had found through the initial 1967 and now 1969 Rabbit and Dog PII studies. However, this did not stop them going forward trying PII on patients at five different Hospitals using three investigators at each Hospitals, soon most of these Investigators started to “pull out” of these arrangements using a range of reasons as to why, with one group stating it was …“Due to pressing duties,….did not enter into any investigational work.”.. . Soon only one group of investigators were left, Drs. E. Ralph Heinz, Ray A. Brinker, and Juan M. Taveras, from the Neurological Institute, New York interestedly they were the same group which performed the above-described pharmacologic 3-dog study. ….” The authors conclude that they “have been better able to visualize the spinal cord utilizing the less concentrated contrast, as well as visualize small differences in density when external compression of the subarachnoid space is present. The authors feel that this less concentrated Pantopaque offers definite advantages over the conventional 30% Pantopaque. However, they offer no objective confirmation of these claims, no individual case reports, and no criteria by which they measure “better” visualization or “small differences” in density’… . [Suzanne Parisian 2002]
Based on the information shared by Lafayette Pharmacal the FDA at that time [without providing the FDA any animal or clinical human study data] concluded that …’ The application is incomplete under section 505(b)(1), in regard to clinical studies, because of failure to report in full investigations that have been made to show whether or not the drug is safe for use and effective in use, failure to include adequate case reports concerning each subject given the drug or employed as a control, and failure to include substantial evidence consisting of adequate and well-controlled investigations’… .
At the bottom of FDA reviewer’s report there is also a handwritten note from A Ruskin dated 5th May 1966 …’should pharmacologic work be complete before and further tests? is there an IND? [Investigational New Drug] ‘… . The FDA reviewer responded stating …’the FDA Division of Toxicological Evaluation [DTE] did request ‘acute toxicity data in perhaps dogs and rabbits ‘ but apparently never performed’… . Today of course we see they were done but never submitted to the FDA as required. [But you can see then below]
On the June 15th 1966 A. R. Casola of the FDA Manufacturing Control Branch [MCB] authored a draft informing Lafayette Pharmacal that their Application was incomplete, stating …’the NDA failed, among many other things, to provide adequate information regarding the qualifications, educational background and experience of the technical and professional responsible for ensuring that the drug had the safety, quality and purity it purported.
Unearthed is a FDA memo between a W. Gyarfas MD of the FDA and Mr Mintener legal representative for Lafayette Pharmacal regarding a visit without an appointment to the FDA Offices to enquire about the status of the IND and the NDA [New Drug Application] Mr Mintener also enquired of Dr Gyarfas what would be required for Lafayette Pharmacal to answer the agency’s letter of October 11th 1966 that had again requested the submission of an over-due progress report of the status of the clinical studies. The inadequacies of the NDA were reviewed with Mr Mintener kept making references to ‘Julius” and “old timers”. Mr Mintener indicated that he would inform his client Lafayette Pharmacal how to bring their IND up-to-date and recommend that they complete their NDA.
At the same time Kodak and Lafayette Pharmacal continues to try and find ways to ‘keep all this under wraps’, concern overseas continue to grow, a July 1957 MJA published in Germany in the Journal Nervenzart it’s titled” Late damage due to contrast media after pantopaque myelography you can find it in volume 38 (7) page 322 – 324. Sadly its not only is it in German, I have to date been able to access a copy.
On the 19th of September 1967 Doctor Embree of Distillation Products Industries [part of Eastman Kodak] wrote to Doctor Jessup at the Hazleton Laboratories Toxicology Division to whilst appear to agree with Jessup’s earlier thought’s shared with them on the 8th. [Copy of details not available] However, the reader here will get the underlying comments being given to Jessup by Embree with this 19th of September 1967 letter. Embree it seems is wanting Jessup to extend the time the dogs after being injected with PII live to six weeks, one wonders why. Here is a copy of that of that two page letter.
No further written correspondence can be found by me regarding what happened next, but my felling is Doctor Jessup basically was ‘pulled into line‘ to what Embree and Fassett wanted. The next letter I have been able to access is dated 7 months later dated April 10th 1968 sent to the Owner of Lafayette Pharmacal Dr Kunz to regarding not this time the previous “adjusted” Dogs studies using PII but the PII Rabbit Teratology Study and the “required” protocol after …’Dr Jessup success in persuading the FDA to accept studies on only one Species for Pantopaque II rather than the two species specified for most new drugs’… Interestingly, one can also see within this letter that the author of this letter being Embree makes reference to the FDA also stating that they would also require similar Teratology Study data on Pantopaque I [currently being sold worldwide] this request would have have put Eastman Kodak and Lafayette Pharmacal in a spin, this is the last thing they would have wanted, owing to such would “let the cat out of the bag”. [Or should that be rabbit] Here is a copy of that letter.
The next letter of two pages obtained is dated April 23rd 1968 sent to Dr Enbree from Dr Fassett at the Laboratory of Industrial Medicine [Eastman Kodak] stating the protocol for PII Rabbit Teratology Study by Hazleton Laboratories and stating the following [found in second last paragraph on the second page] …’I would recommended that before a final decision is made the matter be re-discussed with the FDA if you think there is any hope of changing their mind in this matter’… . Here is that two page letter.
The following day [24th] Dr Embree send a letter to the Owner of Lafayette Pharmacal c.c. to Jessup stating that [once again] changes have been made and makes reference to the letter above. He then goes on to say …’I shall try to telephone you Monday morning, April 29th to review this matter with the expectation that one or both of us will talk later in the day with Dr Jessup’… . Its quite clear who is steering this ship. Here is that Letter.
The next month being May a meeting took place between representatives of the FDA, Lafayette Pharmacal and Hazleton to discuss the animal tests however, due to serious CNS toxicity the cause was blamed not on the toxic nature of PII [at half strength of that was being sold around the world as well as America, but to ‘mechanical effects’ of the injection rather than the chemical (toxic) effect.
Seven months later Dr Jessup writes to Dr Embree enclosing a copy of the pathologist report for the intrathecal dog study of Pantopaque I and Pantopaque II. Dr Jessup whilst suggesting that there were problems due to the administration of PII he continues to blame the mechanical nature of the effects rather than PII itself. However he goes on to state …’In the final analysis, it appears that there are NO [my capitals] systemic effects on the fetuses’… . Please see a few pages of the final report [later into this blog] to see this is a direct lie, in fact criminal. Here is that letter.
Three days later Dr Embree writes to Dr Fassett at the Laboratory of Industrial Medicine [Kodak Park Division of Eastman Kodak] where he writes among other things the following …’I should like to discuss it’… [my words, the dog studies PI & PII results] …’along with the report on Hazleton experiments on this subject’… . Its clear by what we know today that Dr Embree is deeply concerned regarding these results [such can be found further below] and is indirectly notifying them “they need to talk off the record“. Letter below.
My sincere thanks to Dr Sarah for the following data [In response to Embree’s erlier letter] …’Fassett, of the Laboratory of Industrial Medicine, wrote back to Embree and put forward the idea that the tested animals (rabbits) had problematic anatomy and that this might result in exacerbating the mechanical adverse effects. He also remarked: “removing a more diluted material might be more difficult…”might expect more side effects due to”…”cellular irritant effects of residual radiopaque.” This clearly demonstrates that Fassett was fully aware of the adverse effects and that he informed Kodak’s subsidiary, Dpi, via Embree. To make matters worse, Hazleton submitted the data from their 15-week intrathecal study in dogs to Dpi rather than Lafayette. It seems never to have reached as far as the FDA. Busey, the pathologist involved, wrote extensively about the severe reactions seen in the study and Jessup outlined effects in various organs (surprisingly omitting mention of effects on the liver). The dogs studied suffered from effects such as: granulomatous meningitis in the brain and spinal cord, fibrosis, thickening of the meninges, meninges adherent to the floor of the vertebral column. The majority of reactions were of a subacute or chronic nature. More systemic effects included pituitary cysts, lung nodules, spleen nodes, reddened renal medulla. The spinal effects were of differing location and severity according to which concentration of dye was used; both Pantopaque I and II were studied. 0.014 ml/kg produced predominantly lumbar lesions, whereas 0.14 ml/kg induced severe cervical and thoracic cord reaction, slightly less in the lumbar region. Jessup’s report also mentions clotted blood at the base of the brain and anterior spinal cord in one dog after Pantopaque and four after Pantopaque II. He also noted “oil material, possibly compound, in areas of the meninges.” (What the material could be other than the dye is hard to imagine!). Needless to say, this type of data was pretty damning not only of the newly proposed product (Pantopaque II) but also its predecessor, the original Pantopaque, which was by now in widespread clinical use and had been for some 20 years or so. One might expect that this type of result would raise alarm bells not only within the pharmaceutical company, but also their associates (Kodak) and not least, the licensing authorities. However, one can only assume that they never saw the light of day, because no further action was forthcoming. The only plausible explanation for this was that these results were SUPPRESSED by the company and/or their associates, who stood to lose a great deal financially if the study results became widely known.
The next piece of information in the huge jigsaw comes from 1969, when Siefe of the FDA wrote to Lafayette to inform them that they had failed to submit any annual reports. [for 25 years added by writer of this Blog] and also that they needed to make various changes in the package inserts. See below
[Original copy of this damning letter added by the writer of this Blog]
Thanks Sarah …’Strangely enough, Lafayette saw fit within the same year to conclude that Pantopaque II had no “real improvement over conventional Pantopaque” and attributed this to the summaries of their three principal investigators, Taveras, Peterson and Fager. Accordingly, on June 25, 1969, the President of Lafayette, Bucke, wrote to the FDA to request withdrawal of NDA 16-377 for marketing approval of Pantopaque II.
It appears that the FDA was not informed of the animal toxicity studies that had failed to support the safety of the original Pantopaque. IND 1-161 also had to be amended, and a ‘notice’ from Lafayette was required to notify the authorities of discontinued clinical studies. This should have included information about “clinical studies that have or will be submitted to the NDA before its official withdrawal.” One assumes this covers the 15-week intrathecal study, but this was seemingly ‘overlooked’. The Lafayette representative, Kunz, who liased with the FDA on this matter, appears to have ‘fudged the issue’ by cross referencing information on clinical studies reported in the NDA to serve as a progress report for the IND, In other words, he was ‘killing two birds with one stone!’ The fact that technically Hazleton had sent the study results to Kodak, not Lafayette might excuse Kunz being unaware of them, except that one would expect him to be cognisant of the studies being undertaken, otherwise he would surely not be the right person in the company to be dealing with the NDA requirements. Had he not been aware of the results, he should have taken the necessary steps to rectify the lack of information. Pleading ignorance hardly seems a valid excuse, especially when the FDA representative, Dr. Grigsby documented in a memo that he has specifically indicated to Kunz that the firm was required to be forthright and honest. One wonders why he felt it necessary to stipulate this statutory requirement so bluntly. Perhaps (and this must be conjecture) he sensed that he was not being told the full story! The 1960s thus drew to a somewhat ignominious close as regards the ‘dark industry’ that continued to profit by the marketing of this highly toxic product. This was the peak of its success, but all achieved dishonestly. Matters were not to improve in the 1970s, when the advent of water-soluble contrast media presented rival products that required even more sterling tactics from the manufacturers, despite a growing body of medical literature. Strangely enough, the 1971 DESI review of Pantopaque failed to highlight the dangers of the product, perhaps because it was aimed principally at efficacy rather than safety. 1971 was also the year in which the Drug Bulletin and the National Drug Experience Reporting System were set up in the USA and when Glaxo changed their package insert to include warnings about adverse effects such as arachnoiditis. They concluded, however, “the sporadic nature of reports, and sometimes the sparseness of information about the patient’s condition prior to myelography make it difficult to evaluate the role of iophendylate. However, …”these reports probably add weight to the case for removing as much Myodil as possible.”… . Now that I shared with you Dr Sarahs comments above I now wish to continue with the following just prior to supporting Dr Sarahs remarks with that of Dr Parisian a x FDA Drug Safety Inspector whom whilst was not at the FDA over the life of Pantopaque I and PII investigated its History and submitted such as a Expert Report in a 2002 Court Action.
We go on.
In February 1969 Hazleton finally completed their intrathecal studies using Dogs and Rabbits which aimed to show LD50 [dose at which 50% of the animals die] and among other things reported the following in their 1969 Report …’motor in-coordination was observed as well as connective tissue lesions’… .
What the reader needs to grasp at this stage is this whilst Lafayette Pharmacal has engaged Hazleton to carry out these PII animal tests on Rabbits and Dogs the horrendous findings by Hazleton [see results below] were withheld as Dr Sarah reporte earlier from them [Lafayette Pharmacal] and provided ONLY to Eastman Kodak. [Distillation Products Industries] This is clearly where the BLAME lies ‘LEGALLY’ with Eastman Kodak.
The next piece of correspondence I have been able to obtain is a letter dated 24th April 1969 from the Owner of Lafayette Pharmacal Dr Burke to the Acting Associate Director for Marketing Drugs for the Bureau of Medicine responding not so much regarding the fact they Lafayette Pharmacal did NOT report any adverse reactions and provide annual reports as required under Regulation 130.13 and section 505j of the Food, Drug and Cosmetic Act to the FDA for 25 years. Bur concentrated their response around the FDA required changes to their Product Insert for Pantopaque, changes that reinforced the need to aspirate, completely disregarding the fact that they the FDA had NO prove Pantopaque was safe and its unforgivable that at the same time the FDA was and had been receiving adverse reaction reports and deaths of patients injected. Its clear that within the FDA much like the TGA in Australia the ‘left hand has no idea what the right hand was doing’. Dr Burke then lies to the FDA by stating that they believe that Pantopaque was …’safe and efficacious’… due to it being on the world market for more than 25 years. He then makes reference to a “collection of MJA’s listed at the end of his letter as support of such a statement.[See page 2 below] Of course what Bucke was not stating to the FDA was Lafayette Pharmacal had been withholding adverse reaction reports being sent to them by end-users and related hospitals etc here in America and from around the world.
On another front, things were also becoming very serious for Eastman Kodak and Lafayette Pharmacal regarding the results of PII at half the iodine content of PI which had showed that PII was also far too toxic for human use. ‘They were in a bind’ for they not only had to submit these PII Rabbits and Dogs results BUT those also requested by the FDA being those for Pantopaque I as well, as part of their application. What could they do?
But before I get to that, its important that you read the information below as referred to earlier, this specific section was taken from a 2002 submitted Court Transcript that was seen and accepted by the Court.as being a ‘Expert Report’ by a Dr Parisan [an x-FDA Investigator] on Iophendylate Pantopaque I and Pantopaque II.
I will also provide you with a full copy this this Report as a PDF file further below.
Here is Dr Parisan findings on PI and PII for both the Dogs and Rabbits as seen below.
My thanks to Doctor Parisian for permission to share. 
On September 7, 1967, Hazelton Laboratories completed an Acute Intrathecal Toxicity Study-Rabbits involving 16 rabbits using Pantopaque II that were followed for 14 days.
The study data was [then] submitted to Lafayette Pharmacal,
[written by myself author of this Blog, Please understand whilst below is the 1969 15 week studies for Rabbits and Dogs, here Dr Parisian is referring to the earlier studies of 1967 NOT those of 1969, I will try and obtain these earlier 1967 studies and post here at a later time]
We continue Dr Parisian Expert Report
The summary of the study went as followed: Pantopaque II was evaluated for acute intrathecal toxicity by intraspinal injection to groups of adult albino rabbits (* 4 groups of 4 rabbits each) at graded dosage levels ranging from 0.562 to 316 g/kg of body weight. Partial mortality at the two lower levels and total mortality at the two higher levels were produced. The mortality pattern did not permit an accurate calculation of the acute intrathecal LD50, but it is estimated to be in the order of 0.5 g/kg of body weight. Principal Toxic Effects Observations noted during the 14-day period consisted of the following: Slight ataxia at the four-hour observation period only in all animals at the lowest level and in two animals at the 1.0 g/kg level, rapid respiration prior to death in one animal at the 1.78 g/kg level, limited use of the hindquarters in two animals, and terminal body weight loss in all animals at the lowest level; partial mortality at the two lower levels and total mortality at the two higher levels.
November 13th, 1967 Hazelton Laboratories submitted Acute Intrathecal Toxicity-Dogs Pantopaque II to Lafayette Pharmacal, Inc.
The investigation had been conducted from July 27, 1967 through September 6, 1967. The summary of the data was as follows: Single intraspinal doses of the test material, Pantopaque II, were administered to four groups of two dogs each, at levels of 0.316, 0.562, 1.00, and 1.78 g/kg, respectively. The dogs were observed for 14 to 20 days after dosing and then sacrificed. All dogs showed signs of muscular weakness and incoordination following dose administration, with particular loss of motor control of the hindlimbs. The degree of this motor incoordination did not appear to be related to the dose level. All animals slowly returned to normal or near normal appearance during the observation period except one low level animal which died after two days, apparently from an injury sustained during injection of the compound. Gross necropsies after sacrifice revealed the presence of oily substance resembling the test material in the cerebro-spinal fluid of all but two animals. Connective tissue lesions in the area of the injection were present in about half the animals. The dog that died had received the lowest dose Pantopaque II dose, Group No. 1, (0.316 g/kg) and had appeared normal on the day of dosing. (*Two dogs were used in each of the 4 dose groups.) On day 2, its behavior became vicious and it was found dead on day 3. The other animal in the low dose group appeared normal for several days following dosing. However, on the day 4, the animal appeared uncoordinated and became partially paralyzed in the hindlimbs. The dog’s condition returned to normal by day 8, but it continued to lose weight throughout the study until termination. For the two dogs in the next dose group, Group No. 2, (0.562 g/kg), both became markedly uncoordinated with partial paralysis in the hindlimbs. Their conditions gradually improved until sacrifice. Group No. 3 dogs (1.00g/kg) both exhibited signs of muscular weakness and poor coordination following dosing. Partial paralysis of the hindlimbs were apparent in both and improved in one animal. A similar picture occurred in the highest dose group, Group No. 4, (1.78 g/kg), with initial muscular weakness, lack of coordination and slow improvement until time of sacrifice. Histologically, all animals in Groups No. 2 and 3 had connective tissue lesions of varying severity found at the location of injection. The dog in Group No. 1, the lowest dose group, that died had hemorrhagic and purulent-appearing areas at the base of the medulla and between the meninges and the spinal cord. The spleen of this animal was enlarged to twice normal size. For all dogs, at autopsy, traces of oily substance, varying in amount approximately proportional to the administered dose level, were found within the cerebrospinal fluid.
Almost two years later, February 7, 1969, Hazelton Laboratories completed the study 15-Week Intrathecal Toxicity Study- Dogs which was a comparison of Pantopaque I and Pantopaque II. The data was submitted to Kodak’s Distillation Products Industries, Rochester, NY, not to Lafayette Pharmacal, Inc as had been done with the earlier studies. The purpose of the study was to evaluate the long-term effects of Pantopaque II when compared to Pantopaque I after being left within the spinal column of dogs. Pantopaque I was a lot that had been received by Hazelton Laboratories from Lafayette Pharmacal on November 27, 1967, Lot No. 129666, and appears that it may have been a production lot. The purity was “assumed” to be 100%. Pantopaque II was identified as ethyl phenylundecyclate combined with 15% organically bound iodine ( Lots No 91347 and No. 91374), and appears that it was an experimental product. It was received July 24, 1967 and November 27, 1967 from Lafayette Pharmacal. The purity also was “assumed” to be 100%.
My words, please see a ‘snapshot’ of a study using 24 purebred Walker hounds [used as part of the PI & PII study. Answers a lot of unanswered questions regarding the suffering experienced by patients injected with Iophendylate [Pantopaque -Myodil etc]
The study used 24 purebred Walker hounds, divided into 2 dosage groups (0.014 ml/kg) or (0.14 ml/kg) of either Pantopaque I or II compounds, for a total of 4 groups. The test material was administered by a single injection into the cisterna magna, with all dogs observed for 15 weeks. Full spine lateral x-rays were made for each dog following injection and at regular intervals of 30 and 60 minutes, 3, 24, and 48 hours, and one to two weeks thereafter. Only the brain and spinal cord were examined microscopically. Five animals that received Pantopaque II at 0.14 ml/kg showed a marked increase in leukocyte counts at 24 hours. Five dogs had clotted blood present at the base of the brain and anterior spinal cord – one Pantopaque I and four Pantopaque II. Eight dogs had meninges visibly thickened three Pantopaque I and five Pantopaque II. In two dogs, both Pantopaque II dogs at 0.14 ml/kg, there were adhesions to the floor of the vertebral column. In 6 dogs, oily material was grossly seen in the meninges- three Pantopaque I and three Pantopaque II. Two Pantopaque I dogs receiving 0.014 ml/kg (No. 12686) (No. 12705) (* the lowest dose) microscopically at autopsy had moderate to severe granulomatous reaction surrounding large vacuoles in the space under the meninges and surrounding some of the spinal nerves. The granulomatous reaction involved spinal nerves. There was moderate to severe fibrosis surrounding the spinal cord and scattered areas of granulomatous reaction were present within the white matter of the spinal cord. Most of the granulomatous reaction was associated around large, clear empty (cystic) vacuoles. The spinal cord was surrounded by moderate amounts of old blood present under the meninges. A Pantopaque I dog that had received the same dose (No.12694) had a similar microscopic picture of granulomatous reaction and fibrosis with cystic spaces but had a moderate amount of fresh hemorrhage under the meninges. Pantopaque II dogs receiving the lower dose level (0.014 ml/kg) appeared to have gross acute bleeding at all levels of the spinal cord and brain. Microscopically there was perivascular infiltration of meningeal vessels and spinal cord involving macrophages and mononuclear cells, and scattered clear cystic spaces. Pantopaque II dogs at the higher dose level (0.14 ml/kg) appeared to induce a greater active inflammatory response component. The granulomatous inflammatory reaction was moderate to severe infiltration of mononuclear cells, macrophages, lymphocytes surrounding clear cyst-like areas, moderate to severe adhesion of the arachnoid and dura mater to the spinal cord. Histologically, sections of the spinal cords resembled areas of severe granulomatous reaction seen with Pantopaque I. Severe granulomatous infiltration extended down to the cauda equina, with moderate thickening of the arachnoid, and areas of compression of the spinal cord.
The following was the summary of Hazelton Laboratories, William M. Busey, DVM, Ph.D.’s findings: The intrathecal administration of Pantopaque I and Pantopaque II to mature Walker hounds produced varying degrees of granulomatous meningitis in the brain and spinal cord. In the majority of instances, in the animals possessing meningitis, the inflammatory reaction appeared to be associated with empty vacuoles which could possibly have been the experimental compounds. In addition to the granulomatous type of cellular infiltration, there were varying degrees of fibrosis and thickening of the meninges of the both the spinal cord and brain. In the group receiving Pantopaque I, at a dosage level of 0.014 ml/kg, subdural granulomatous inflammation was present to a moderate to severe degree in three animals. Only a slight to moderate amount of granulomatous inflammation was seen in three of the animals receiving Pantopaque II at 0.014 ml/kg. A slight amount of granulomatous inflammation was present in the cervical and thoracic regions of the spinal cord in Animal No. 12700. There was, however, in this animal, a moderate degree of meningitis in the brain which was associated primarily with two vacuoles in the region of the medulla oblongata. There did not appear to be any difference in the incidence or severity of granulomatous meningitis between the animals receiving Pantopaque I at 0.14 ml/kg and those receiving Pantopaque II at 0.14 ml/kg. Severe granulomatous meningitis was seen in the cervical regions of all of the animals in these two test groups. In addition to the inflammatory cellular infiltration, there was severe fibrosis in this region of the dura mater and arachnoid. …’The majority of the animals receiving Pantopaque I and Pantopaque II at 0.14 ml/kg also possessed some degree of meningitis of the brain’… .
Angry yet readers?
Lets continue the summary of Hazelton Laboratories, William M. Busey, DVM, Ph.D.’s findings: In conclusion, it can be stated that the intrathecal administration of Pantopaque I and Pantopaque II at 0.014 ml/kg and 0.14 ml/kg stimulates a granulomatous meningitis (*bold and italics added for emphasis) in the areas where the compounds appear to localize. The majority of the inflammatory reactions present in the animals on this study were of a subacute to chronic nature. There was a definite difference in the location and severity of the inflammatory reaction between the two dose levels. The dosage level of 0.014 ml/kg of Pantopaque I stimulated a granulomatous reaction in primarily the lumbar region; whereas, the dosage level of 0.14 ml/kg of both Pantopaque I and Pantopaque II produced severe reaction in the cervical and thoracic cords. Granulomatous inflammation was also present in the lumbar cord but to a slightly less degree of severity and incidence.
On February 10, 1969, Hazelton Laboratories submitted the final report of the Teratology Study with Rabbits and Pantopaque II to Distillation Products, Rochester, NY. The purpose of the study had been to evaluate the potential of Pantopaque II to produce embryotoxic and/or teratogenic effects in a study population of albino rabbits. Peanut oil was administered as a control injection to Group No. 1, Pantopaque I to Group No. 2, and Pantopaque II to Group No. 3 rabbits. Each experimental group, which consisted of 40 rabbits, was divided into four subgroups of 10 animals each. The first subgroups received a single dose of the appropriate injection two days prior to insemination; the second subgroups received a single dose of the appropriate injection on Day 5 of gestation; and the third and fourth subgroups were injected on Day 8 and Day 11 of gestation, respectively. The study was begun on June 25, 1968, with sacrifice of the last groups of females completed on September 6, 1968. The final results indicated that there were no meaningful differences between the peanut oil, Pantopaque I and Pantopaque II groups in the number and placement of implantation sites and live fetuses, in the weights and lengths of the fetuses, or in the incubation survival. Females with implantation sites unaccounted for were found in the peanut oil and Pantopaque I groups. The number of resorption sites and incidence of females with resorption sites were high in both the Pantopaque I and II females. The mean value of dead fetuses in the Pantopaque I group was high; (* bold added for emphasis) however, one female only was found with dead fetuses, and the value for this parameter was within normal limits. No dead fetuses were found in the Pantopaque II group. No unusual findings were noted in the external appearance or gross visceral anatomy of any of the fetuses. [My words, please read the 3 pages further below which was taken from the final report ‘you decide’!!!]. The development and skeletal structure of the Pantopaque I and Pantopaque II fetuses were comparable to that the peanut oil (control) fetuses. Therefore, the response for Pantopaque II was essentially the same as for Pantopaque I.
Dr Suzanne Parisian Paper as a PDF file.
To go directly to where the beginning of Pantopaque is documented see page 6>
I went back to my research data to dig out a copy of a 1967 Product Insert for Pantopaque II [see below] which I have been able to source, where the following can be found …’Pantopaque II in rats given intraperitoneally caused ‘no deaths and no toxic effects’ and intrathecal injections in rabbits gave to “no…unusual or delayed damage to the spinal cord”‘… . Play on words, or should I say blatant lies, with great consequences.
Copy of the 1967 PII Product Insert
[place copy here]
After re-reading the 1967 Pantopaque II Product Insert and the written data by them of ...’no deaths’… found in all Rats and …’no toxic reaction’… in the rabbits used, I became very concerned regarding the lies being told here so I decided to dig out the 1936 rat study which I had [it was withheld from the FDA] and compare [you can do likewise] its titled: Acute Toxicity of Ethyl Iodophenylundecylate Given Intraperitoneally to Rats. Amazing how the 1967 Product Insert states …’Pantopaque II in rats given intraperitoneally caused ‘no deaths and no toxic effects’… when the 1936 Rat Study [withheld] shows horrendous toxic effects and deaths in all Rats whatever the dose as you can see below in the PDF file titled Intraperitaneally.
Here below is that 1936 Rat Study for you to compare as a PDF File.
Now please see the cover and then two pages of 80 pages of the Rabbit 1969 study which was done NOT to report on any delayed damage to the rabbit spinal cord which is referred to, being the 1967 Study but Rabbit Fetuses after the Pregnant Mother Rabbit had been injected with Pantopaque II.
Please be WARNED the content is horrendous and disturbing.
Now see the 1936 Rabbit Study below, you compare
Based on the findings above, one would think that to go ahead and injected it into the amniotic sac of pregnant women before they gave a unborn child a blood transfusion would be a definite NO, but sadly they did, here’s a photo of how they did it, the dark area around the baby is Pantopaque.
NOW HERE BELOW IS THE FRONT COVER OF THE 1969 15 WEEK INTRATHECAL TOXICITY STUDY USING PANTOPAQUE I OR PANTOPAQUE II IN DOGS.
BELOW THIS COVER IS A PDF LINK TO THE FULL COPY OF THIS STUDY.
This 15 week Dog Study above was carried out not for altruistic reasons but to try as I said earlier to reduce the toxicity of Pantopaque that now had been directly linked to Chemically Induced Adhesive Arachnoiditis, just as Lipiodol had previously. Eastman Kodak and the manufacturer Lafayette Pharmacal aware that Pantopaque was also causing Chemically Induced Adhesive Arachnoidits just like Lipiodol in a wide range of Animals [see the Animal tests referred to above] but also in Humans they didn’t care, they just continued to manufacture and distribute it throughout America and around the world for ‘MONEY’.
Here is a full copy of this Study as a PDF File.
Below is the Summary for those who wish to ‘cut to the chase’. [3 pages]
In fact whilst Kodak and Lafayette Pharmacal are trying to find a way to ‘hid’ PII results, it as I reported earlier it wasn’t until 1969 that the FDA realized they had not received any further correspondence from Lafayette Pharamacal since their PII application, and later its withdraw. Lafayette Pharmacal later that year realizing that PII was far too toxic even at half the strength of P1 that to go forward with PII would expose pantopaque I something they could not let happen. But far more important as I also mentioned earlier Lafayette Pharmacal had NOT provided the FDA with any Annual Reports or any Adverse Reaction Reports for Pantopaque I since being awarded the License to Market Pantopaque 1 in 1944 over 25 years earlier.
This non-enforcement of Regulation 130-13 and Section 505(j) of the 1938 Federal Food, Drug and Cosmetic Act by the FDA is clearly where the FDA failed us all.
By this time Eastman Kodak and Lafayette Pharmacal were becoming very worried concerning the increasing adverse reactions being reported to them, and the “rumblings” being heard from those using Pantopaque not only here in America but around the world as you read earlier. Furthermore, more and more MJA’s from around the world were reporting their concern regarding this substance, as well as other MJAs that the writer of this Blog believed had some relationship to the broader ‘PICTURE OF WHAT HAPPENED AND HOW’. “where was the FDA”? For a comprehensive list of related and indirectly related available MJA’s over that period please follow this PDF below.
Its now May 6th 1969 and one would think that Eastman Kodak and Lafayette Pharmacal are “on the ropes” but as they haven’t provided the FDA with the PII Rabbits and Dogs 15 day toxicity studies as required by the FDA the FDA has no idea what is going on. Or do they? As you can see within this letter below Marvin Seife Acting Associate Director for Marketing Drugs at the Bureau of Medicine within the FDA informs Lafayette Pharmacal that they have instigated an evaluation of the …’the evidence of this drugs effectiveness’… [Drug being Pantopaque] by the National Academy of Sciences – National Research Council. [Please read the letter below in full to grasp what is happening, I ask this, so you can “understand what comes next]
As an requirement of any company applying for a NDA [new drug application] on a ‘withdraw’ of such application they are required to provide ALL animal and clinical related trials/tests. Based the one of the 5 groups of three investigators Taveras, Peterson and Fager all others had withdrawn from the trials/tests for its reported by some as “work related”. …‘The question one needs answers to, is did Kunz the owner of Lafayette Pharmacal know of the PII results of the 15 week Rabbit and Dog tests, whilst evidence shows that Hazleton whom carried out these tests provided the results to Kodak NOT Lafayette Pharmacal. Does this excuse Kunz no, he was Lafayette Pharmacal representative when dealing with NDA requirements with FDA. Had he not been aware of the results, he should have taken the necessary steps to rectify the lack of information’… . …’Pleading ignorance hardly seems a valid excuse, especially when the FDA representative, Dr Grigsby documented in a memo that he has specifically indicated to Kunz [owner of Lafayette Pharmacal] that his firm was required to be forthright and honest’… . [Dr Sarah]
On the 14th of May 1969 a Review of Lafayette Pharmacal took place regarding their supplement giving the reason as wishing to Revise their labeling S-002 for Pantopaque as instructed by the FDA. [See above April 19th 1969] However, this was seen as unacceptable by the FDA given the reason as …’incomplete’… . See copy of letter below.
The next letter I have been able to find is dated the 27th of May 1969 from Malvin Seife Acting Associate Director for Marketed Drugs Bureau of Medicine FDA. Sadly as you can see the copy is poor
I have decided to try and re-write this as quality is very poor, so here goes.
Attention Mr W E Bucke
Gentleman, We acknowledge the receipt on April 27th 1969 of your supplement new drug application dated April 24th 1969, submitted pursuant to Section 505 (i) of the Food, Drug and Cosmetic Act for Pantopaque (Ethyl Iodophenylundeylate) Sterile Solution. The Supplemental Application is incomplete under section 505 (b) (?) of the Act in that it fails to correct the deficiencies as noted in our letter dated April 24th 1969. ???? the Supplemental application is incomplete under Section 505 (b) (?) of the Act, it may not be filed as a application provided for in Section 505 (b)
Signed Marvin Seife
On the 7th of July 1969 Lafayette Pharmacal sends an official letter to the FDA informing them that they would be discontinuing PII NDA. The contents of this letter is critical for the reader to understand, whilst Kunz of Lafayette Pharmacal states in this letter that 3 volumes in triplicate of data regarding the withdraw of NDA 15-377 and IND #1161. What was NOT provided was the damning 15 week Rabbit and Dog study using PII and the horrendous findings. Please note the date of this letter being 7th of July, stamped the 10th of July which is nearly 2 weeks after Kunz’s stated date delivered being 27th of June. In fact, it would be almost 9 months before these Rabbit and dog studies are delivered but NOT to the Offices of the FDA of Marvin Seife BUT to the FDA Archives where it was accepted, unchecked and placed into Storage.
Only to be inspected by Dr Parisian in 2002 33 YEARS LATER.
But let’s step back a moment, In 1962 seven years before the FDA became aware that Lafayette Pharmacal had NOT provided to them any Annual Adverse Reaction Reports regarding Pantopaque, but worse still, NO recorded deaths of patients after being injected with Pntopaque as required under the Food, Drug and Cosmetic Act. I raise this because when the FDA found out that Lafayette Pharmacal had not provided these Annual Adverse Reaction Reports and Deaths since Pantopaque gained its General Marketing License back in May 1944, 25 years earlier, ‘alarm bells went off’. As you recall I made mention of JFK signing the 1962 Kefauver-Harris Amendments to ensure that …’before marketing a drug, firms now had to prove not only safety, but also provide substantial evidence of effectiveness for its product’s intended use’… Due to the FDA not receiving any Annual Adverse Reaction Reports and Deaths for Pantopaque since issuing the NDA approval to market, they instigated a DESI review. The following has been taken from Doctor Parisian Expert Report with permission.  …’Uncertain about the safety of America’s drug supply continued even after the passage of the Kefauver-Harris Amendments. As a result, Congress opened hearings in March 1964, chaired by Representative L.H. Fountain, to investigate FDA’s efforts to promote drug safety. But Fountain’s hearings took a comprehensive look at the agency’s regulation of drugs, especially those that were removed from the market. To further comply with the requirements of the drug amendments of 1962, the FDA contracted with the National Academy of Sciences/National Research Council (NAS-NRC) in 1966 to study all drugs approved from 1938-1962 from the standpoint of efficacy. [S. Parisian 2002]
What is very clear when you read this 1971 Pantopaque DESI Report is that their review …’failed to highlight the dangers of the product, perhaps because it was aimed principally at efficacy rather than safety’… . [Dr Sarah] Interestingly, if one researches what was also happening at this time 1971] in America one finds that the Authorities had set up a Drug Bulletin and the National Drug Experience Reporting System. If one now visits a Product Insert not for Pantopaque BUT Myodil being the same product but produced by Glaxo UK you will find the following Product Inserts from 1971 onwards. I will place each as a PDF ok here is the first of being 1971 the last 1988
As you can see Glaxo Myodil Product Insert has changed from their 1967 Product Insert to now include the following …’serious after effects are rare’… …’Occasionally arachnoiditis has been reported but that type of reaction has not been associated with a specific disease or technique of investigation’…’ …’the sporadic nature of these reports and sometimes the sparseness of information about the patient’s condition prior to myelography make it difficult to evaluate the role of iophendylate’… [What did they do investigative wise to ensure ‘no relationship’ none,!!!] Glaxo finishes off with the following …’these reports probably add weight to the case for removing as much Myodil as possible’… .
What is scary, and shows the lack of concern by the developer Eastman Kodak and the Manufacturer Lafayette Pharmacal is of the toxic nature of this substance when they “encourage” end-users to increase the dose used, ‘more and more profit’ disregarding any harm such would cause in fact, some end-users were using up to 100 c.c. Here below are a three MJA’s promoting such use. [NO FDA approval of such use, can be found] The first was dated 1958 and promoted at the 44th Annual Radiological Society of North America what wasn’t stated there was such use was NOT approved by the FDA and NO animal studies of such dose had taken place.
Here is that MJA
If you have got this far and wish we to continue with this blog for 1969 onwards
please make contact.
THIS WHERE THE BLOG IS UP TO, STILL SO MUCH TO DO