Where a question mark appears the text is questionable.
Where a question mark appears beside a word or letter that word or letter is a best guess.
Where a consecutive series of dashes appears the word is unreadable.

Memorandum of Interview

September 9 1941

Present: Dr W. H. Strain, of the University of Rochester, School of Medicine and Dentistry, Rochester, N. Y.
Dr Walton Van Winkle, Jr
Dr ?.F(?) Kennedy

The visitor called to discuss a new contrast medium for radiography of body cavities which is being developed by the University of Rochester. Dr Strain stated that the preparation has been disignated "Pantopaque", the chemical name of which is ethyl iodophenylundecylate. He(?) stated that the drug is to be used in radiography of the spinal canal, sensory(?) nasal sinuses, the common duct, and the fallopian tubes. Dr. Strain stated that this chemical has been under study for the past two years in the chemical laboratories, that pharmacological studies on dogs and other animals also have been in progress for the same length of time, and that 15 intrathecal injections have been made. He stated that the advantage of this preparation over those now proposed for the same use is that his product is absorbable, whereas substances like Lipiodol remain in the site of injections for the duration of the patient's life. He then discussed the various cases in the which the drug had been injected intrathecally and pointed out that only one case had experienced a reaction. This reaction had consisted of a ----cytosis, altration of temperature, and caudal(?) pain. He stated that, in experimentation with the chemical in rabbits, the injection of it into a ---- of the ----- had been followed in 33 percent of the cases by a sloughing of the ---------trium. No clinical studies as yet have been done on use of the drug in sinuses or common duct.

Dr. Strain then stated that neurosurgeons were reluctuant to use Lipiodol (an iodised poppy seed oil) since it had been demonstrated that this preparation becomes encysted in the spinal canal. He stated that two prominent neurosurgeons had become interested in the use of Pantopaque, namely, Dr. R. Glen Spurling of Louisville, Kentucky, who has injected the drug intrathecally in 6 cases, and Dr. Eric Oldberg of Chicago Illinois. He stated that they hoped to have at least 100 intrathecal injections of this material prior to submitting a new drug application , and requested comment as to our opinion concerning the adequacy of this number. It was pointed out to Dr. Strain that this 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. Dr. Strain was told that obviously the number of cases selected should be proportional to the frequency with which a procedure such as this would be used in medicine. He also pointed out that it would appear desirable for more than two investigators to submit reports of of clinical use of this drug.

Page 2 (Memo of Interview - Pantopaque)

Dr. Strain then asked for comment form us concerning the quality and quantity of the pharmacological and clinical evidence which he had previously recited. He was told that we should like to have complete data on the fatal dose of the preparation not only when given intrathecally, but also when given parentarally(?) and by mouth, since, when used for visualisation of the nasal sinuses most of the material will be ultimately 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 administrations 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 inwhich it is proposed to use it. We suggested that a simple comparison of its ablility to produce irritation, as compared with like substances, could be made by using a frog muscle nerve preparation and applying this material in various concentrations in spinal fluid to the exposed nerve and noting the amount required and the time of onset for muscular twitchings to occur. Comparisons could be made with plain 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 of irritation with this material, using the rabbit's eye as a test object. Additional pharmacological evidence, including the rate of absorption from intramuscular injection,
intrathecal injection, and oral administration, together with complete histological studies of the animals used - particularly those showing any reactions to the material - should be submitted.

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 the various investigators was then submitted, reading as follows:
6 Ampoules - 10 cc. Size - Sterile
Pantopaque Contrast Medium for
Radiography of Cavities - Do not
Expose to Sunlight

"Caution: New Drug - Limited by Fed-
eral Law to Investigationer's Use"

Prepared and Distributed by the De-
partment of Radiography, School of
Medicine and Dentistry, University of Rochester, Rochester, N.Y.
Each Ampoule Contains Sufficient For the Withdrawal and Administration
of 10 cc

NOT FOR INTRAVENOUS USE

A third sheet of paper is attached in handwriting. My experience as a Leading Writer (Administrator) in the Royal Navy suggests that this is the minute sheet which would have been attached inside the front cover i.e. left side. The document itself would have been on the right side. This sheet is known as the "Minute Sheet" and would have been used during the circulation of the file within the FDA.

The handwriting is not clear, I will apply the same rules as those used in the transcription of the typewritten document. In the interests of reading clarity I have double spaced the text and my remarks appear under the translated black text, those words which I cannot translate are treated the same as in the text above.
By Van Winkle,

While the material perhaps has advantages over Lipiodol it also would appear definately more dangerous to use.

The clinical reports and the animal work undoubtedly i-dix that something in the preparation is capable of setting
(indicates?)
up definite(sic) meningismus(?). The similarity of these symptoms to those suffered by patients injected with
(underneath the word "symptoms" is another which is lined through, it appears to read "reactions")
Winthops Pyrogen Pontocain combination raise the question as to whether they have taken any precautions to

Sc----- of ye-g---(?). Certainly any ------(?) for intraspinal injection ought to be pyrogen free. It is probable that

Lipiodol doesn't contain much in the way of pyrogens because it is an oil and would have little affinity for

pyrogens. Also the intense foreign body reaction around cysts of the material is disturbing.

It would be interesting to know the temperature reactions after filtrating(?) this Scity a E-til(?) 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 wonder if physical constants given are adequate to ensure uniformity of composition. In

regard to stability there is nothing said other than that the material darkens readily if exposed to sunlight. Is any

free iodine liberated? If so is the material contra-indicated in such diseases as --perthy------(?) - I assume they

haven't had time to answer the last paragraph of you letter of Nov 9 1943(?).

Their so called assay(?) is not very satisfactory since almost anything is allowable except death of the animal.

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