Chapter XV: Introduction: The Council on Pharmacy and Chemistry was established (8)

Casta-Flora is one of those complex preparations which are offered to the medical profession, with plausible arguments in support of the claims made. It is put out by the Wm. S. Merrell Chemical Co., Cincinnati. Each fluidounce is said to represent:

“Castanea, fresh leaves, 40 gr.; Passiflora, fresh plant, 40 gr.;
Gelsemium, green tincture, 8 minims; Inula, represented by the
camphoraceous stearoptene Helenin, 20 grs.; Iodized Lime, 8 grs.;
Menthol, 1-4 grs.; Aromatic Syrup Yerba Santa, 60 minims.”

It is said to be:

“A new combination of well-tried remedies of especial value in
pertussis and other spasmodic coughs. It is composed of astringent,
antispasmodic, sedative and expectorant agents, that control the
paroxysms, relieve the irritation, promote expectoration, and give
tone to mucous membranes involved.”

Still more exaggerated claims are made for the individual constituents of Casta-Flora, partly by direct statement, partly by inference. For example:

“Castanea is almost a specific in whooping cough and other
spasmodic coughs.

“Passiflora is a narcotic, sedative and antispasmodic without
habit-forming properties, nor does it lock up the secretions and
upset digestion like opiates.

“Inula (elecampane) has been employed as a cough remedy in England
for centuries. Its action is similar to guaiacol and creosote. Its
active principle, helenin, is destructive of tubercle bacilli in
dilutions of 1 to 10,000.

“Iodized Lime, Menthol, and Yerba Santa are too well known as
expectorants and antiseptics to require more than passing mention.”

That Casta-Flora is a “new” combination may be admitted; it is improbable that exactly this combination of obsolete drugs was ever before selected for any purpose whatever, but the statement is misleading in that no new principle of therapeutics is involved. On the contrary, the combination is just what might be expected from haphazard choosing of discarded and nearly forgotten drugs. It seems incredible that a reputable firm of manufacturing pharmacists would make the positive statement that castanea is _almost_ a specific in whooping cough. Why not say it is a specific? It would be about as true. A specific or “almost specific” for this disease would rank among great medical discoveries; but castanea is merely a slightly astringent drug neither better nor worse than scores of other astringent drugs that have been tried, found valueless and discarded.

Hardly less surprising are the statements regarding passiflora. This herb has been on the market about three quarters of a century. Not only has it never established itself in scientific medicine, but it is not even mentioned in modern standard works on therapeutics.

Of all the statements made in the circular perhaps the most remarkable, in that it is so dangerously misleading, is that regarding helenin, the active principle of elecampane. The statement that this principle (helenin) is destructive of tubercle bacilli in dilutions of 1-10,000 can only mean that it is of extraordinary value in the treatment of tuberculosis; in fact, it is definitely stated that the action of elecampane is similar to that of guaiacol and creosote.

It is obvious that any drug which would destroy the tubercle bacilli in the human lungs without exerting a toxic action on the patient would be a great contribution to medicine. But although elecampane may have been used for centuries it has proved to have little, if any, merit, and even the National Standard Dispensatory, p. 848, says: “Elecampane was formerly employed as a tonic, stimulant, diuretic, diaphoretic, expectorant, and emmenagogue, but has now largely fallen into disuse.” One looks in vain in the standard textbooks on therapeutics for a description of the uses of inula (or elecampane), and of its so-called “active principle,” helenin.

The circular to which reference has been made says, referring to the use of castanea and passiflora in the treatment of whooping cough:

“Gelsemium, when made from the fresh, green plant--as is
Merrell’s--is an excellent adjuvant to the above drugs, and allays
the nervous irritability so frequently present.”

H. C. Wood, Jr. (Pharmacology and Therapeutics, 1916, p. 160), says of gelsemium: “Gelsemium was originally employed as an arterial sedative and febrifuge in the malarial fevers of the South, and subsequently in sthenic fevers. It appears in some way to depress the bodily temperature, but it does not appear probable that any advantage to be derived from it will counterbalance the danger attending its employment in the large doses required. In asthma, spasmodic laryngitis, whooping cough, and nervous cough it has been recommended by Bartholow, but is little used.”

That is about as favorable a statement for the drug as is to be found in the textbooks, and it serves to illustrate how little new there is in this mixture of obsolete drugs that Merrell seeks to market as one possessing extraordinary therapeutic value.

Even though the ingredients, or certain of them, were singly useful in the treatment of those conditions for which Casta-Flora is recommended, no one could possibly foresee the effect in any given case of such a jumble of drugs, both active and inert, as is said to be represented in this preparation. The prescribing of such mixtures, the action of which cannot in any way be foreseen, is plain charlatanism.

In addition, the various drugs in Casta-Flora are present in such proportions that the dose of each of the several ingredients bears no relation to the commonly accepted dose.

Casta-Flora is not acceptable for New and Nonofficial Remedies.--(_From The Journal A. M. A., Jan. 27, 1917._)

FIRWEIN

Report of the Council on Pharmacy and Chemistry

Firwein is a product of The Tilden Company, New Lebanon, N. Y. It is sold under the claim that when swallowed it has a “predilection” both for the bronchial mucosa and also for the genito-urinary organs. To quote:

“Expectorant, Sedative, Antispasmodic in the Treatment of
Inflammations of the Bronchial and Genito-Urinary Mucosæ.”

“Firwein being a bland, soothing balsam possesses a wide range of
adaptability and increased potency because of its healing virtues
and usefulness as an expectorant, sedative and antispasmodic in
bronchitis, and inflammation and catarrh of nose, throat and lungs.”

“Firwein has a special predilection for mucosæ, this being as
marked in diseases of the genito-urinary system as it is in the
respiratory organs. In inflammatory diseases of the genito-urinary
organs, its bland, curative properties are exerted in a gratifying
degree. In cystitis and uritis it is clearly indicated....”

Little information is given concerning the composition of Firwein. An old circular says:

“Firwein contains Phosphorus, Iodin and Bromin finely blended with
a balsameous elixir made from the fir tree.”

From a more recent circular we quote:

“Firwein is prepared from the inside fresh green bark of the fir
tree ...”

The label on the product reads:

“Firwein is pleasantly and effectively blended with salts of iodin
and bromin, held in solution with 20 per cent. alcohol.”

The therapeutic claims made for Firwein and the mystery enshrouding its composition make it obvious that the product is intended to appeal to those who are either thoughtless or ignorant. This is emphasized by the suggestion that Firwein be combined with (1) cod liver oil (under the claim that it will “promote the efficiency of the oil”), with (2) whisky for the treatment of bronchorrhea of the aged, and with (3) syrup of hypophosphites for the treatment of persistent bronchitis.

As the composition of Firwein is secret, the therapeutic claims unwarranted, and its use irrational, the Council declared it inadmissible to New and Nonofficial Remedies.--(_From Journal A. M. A., Feb. 17, 1917._)

FIROLYPTOL PLAIN AND FIROLYPTOL WITH KREOSOTE

Report of the Council on Pharmacy and Chemistry

Firolyptol, another product of The Tilden Company, is, we are told, composed of eucalyptol 10 drops, cottonseed oil 1/2 ounce and Firwein enough to make 1 ounce. As the composition of Firwein is secret, it is evident that the composition of Firolyptol is also unknown, except to the manufacturers. “Firolyptol with Kreosote” is said to contain, in addition to whatever may be the component parts of Firolyptol, 10 minims of creosote to each ounce. According to an advertisement, Firolyptol with Kreosote is “antituberculous, antistrumous” and “contains all the desired features of cod liver oil and is readily assimilated.”

The advertisements of “Firolyptol Plain” and “Firolyptol with Kreosote” seem to have for their key-note the assertion that cottonseed oil is a particularly valuable nutriment and that when combined with constituents of Firolyptol and Firolyptol with Kreosote becomes particularly valuable to the tuberculous. To quote from an advertising circular:

“Now that the reconstructive properties of cottonseed oil are
better appreciated by the profession, the advantages that follow
the administration of a palatable emulsion of this strengthening
and fattening food product are being demonstrated in hundreds
of cases where formerly reliance would have been placed in cod
liver oil.... A recent writer says that pure cottonseed oil is
the greatest and purest vegetable oil known to chemistry, and
will do much toward revolutionizing the treatment of the GREAT
WHITE PLAGUE.... If the treatment of tuberculosis could resolve
itself into the administration of a fatty substance in a readily
assimilated form, there would be no need for any part of FIROLYPTOL
but the Cottonseed Oil.... The toxic material constantly produced
in the system by the germs of tuberculosis tend to expose it
more and more to the ravages of the disease, and the physiologic
functions of the body suffer a constant depression. To neutralize
this germ activity with a consequent production of toxins it seems
most logical to employ such agents as have demonstrated their
suitability for such purposes, for which reason Eucalyptol and
Kreosote with Firwein are incorporated in FIROLYPTOL.”

The assertion that cottonseed oil is an especially valuable form of fat is without warrant, but even if it were true the fat is available in cheap and palatable forms in numerous other cottonseed oil products. It is unnecessary to discuss the problematic value of creosote in the treatment of tuberculosis or the value of eucalyptol (now generally abandoned), or even of the secret mixture Firwein. Food and fresh air, not drugs, constitute the fundamentals of the treatment of tuberculosis, and it is both irrational and detrimental to the interests of the tuberculous to administer various potent agents in fixed and unknown amounts with such simple articles of food as cottonseed oil. Neither of these products is acceptable for New and Nonofficial Remedies.

Editorial Note.--Firwein[110] has been advertised to physicians for twenty-five or thirty years and it is a sad commentary on the intelligence of our profession that a preparation sold under such obviously false and misleading, not to say silly, claims, should still be in existence. Firwein is claimed to “prevent waste of tissue” in tuberculosis. If it had this power, it would have found its place long ago among the few great agents in drug therapy. As a matter of fact, Firwein has gained virtually no recognition outside of the “literature” of the Tilden concern. The claims made for Firwein are a peculiar mixture of studied candor--when the truth is not likely to hurt its sale--and inane vaporing--when the facts would not redound to its credit. The Tilden Company declares that “Firwein stands without a peer in its class.” But the company adds 10 drops of eucalyptol and some cottonseed oil to this peerless product and an improvement is born--“Firolyptol”! Then, to perfect the already perfectly perfected, 10 drops of creosote are added to “Firolyptol” and the profession is offered “Firolyptol with Kreosote”! In just what verbal pyrotechnics the Tilden Company might indulge, should it decide to add ten drops of something else to “Firolyptol with Kreosote,” one shudders to contemplate.

[110] Three other Tilden products have been the subject of deserved and unfavorable comment in the J. A. M. A: “Narkine” in the issue of Oct. 24, 1908, “Hydrocyanate of Iron-Tilden” in the issue of June 19, 1909, and “Febrisol,” in the issue of June 29, 1912. The first two articles are reprinted in the latest (9th) edition of “The Propaganda for Reform.”

If we are accused of exhibiting undue levity in discussing a therapeutic problem, we can only answer that it is impossible to consider seriously the Charlie Chaplins of the nostrum world.--(_From The Journal A. M. A., Feb. 17, 1917._)

BINIODOL

Report of the Council on Pharmacy and Chemistry

In accordance with the usages of the Council, the report which appears below along with the reports of the clinical investigation by Drs. Cole and Keidel upon which the recommendations of the referee were based were sent to the manufacturer for comment. The reply of the manufacturer contained no evidence which justified the Council in modifying the action already taken. Publication of the report was therefore authorized.

W. A. Puckner, Secretary.

Biniodol was submitted to the Council by the manufacturer, Charles C. Yarbrough, Memphis, Tenn. The manufacturer claims the product is a solution of 1 per cent. of red mercuric iodid and 2.75 per cent. of guaiacol in bland vegetable oil. It is marketed with the implication that it is new and superior to other oil solutions of mercuric iodid. For instance:

“... it is a straight solution of this mercurial compound, as
no alkaline iodide or other chemical is used to bring about the
solution.” “... It is probably the first and only one-percent oil
solution of straight mercury biniodide made in America....”

[The manufacturer, in a letter addressed to the secretary of the
Council, explains: “By straight solution, I mean that the solution
of the red mercuric iodid is effected without the aid of any
alkaline iodid or other chemicals.... Biniodol was first offered
early in 1912 ...”]

“Biniodol is, therefore, superior and much to be preferred to
other mercurials used for like purposes. It is highly active
therapeutically, producing the desired effects, usually without
the inevitable disadvantages of other mercurials. It rarely causes
salivation, diarrhea, or other symptoms of mercurial intolerance,
even when pushed to full therapeutic effect and when given for a
considerable period of time. Nor does it produce anemia.”

The Chemical Laboratory of the American Medical Association found that Biniodol contained 1 per cent. of mercuric iodid and 2.5 per cent. of guaiacol; hence the composition is essentially as claimed. It is not true, however, that Biniodol is the “first and only one-percent solution of straight mercury biniodide made in America.” As shown in The Journal A. M. A., Dec. 9, 1914, p. 2247, formulas by Lemaire and Dunning for making a “straight” solution of mercuric iodid were published in this country in 1909 and 1910, respectively. Moreover, a 1 per cent. solution of mercuric iodid in oil is on the market and is described in New and Nonofficial Remedies.

To determine whether or not Biniodol is “superior and much to be preferred to other mercurials used for like purposes,” the Council secured the cooperation of the Department of Dermatology and Syphilology of the Western Reserve University cooperating with the Cleveland City Hospital, and of the Johns Hopkins Hospital. Each received three samples, labeled respectively, 1, 2 and 3: 1 contained Biniodol; 2, a 1 per cent. solution of mercuric iodid in oil; 3, a solution made up according to the formula of Biniodol, namely, 1 per cent. of mercuric iodid and 2.5 per cent. of guaiacol in oil. All the solutions were sterile. The investigators were not informed which preparation was designated by the respective numbers, but they were asked to use the preparations when intramuscular injections of a 1 per cent. oily solution of mercuric iodid were indicated, and to note what differences, if any, were observed following the use of the different solutions regarding pain, discomfort, induration and any other evidences of effects of the medicaments.

The Cleveland investigator reports that the patients were more or less confused in their replies to inquiries and gave rather indefinite and conflicting answers. After carefully tabulating the replies, however, the following summary resulted:

1 was worse than 2 or 3 in 6 cases.
2 was worse than 1 or 3 in 5 cases.
3 was worse than 2 or 1 in 1 case.

The report from Johns Hopkins records a series of 117 injections followed by the estimated reactions recorded below:

1. Severe, 13; mild, 14; none, 4; unrecorded, 8 = 39
2. Severe, 5; mild, 15; none, 16; unrecorded, 5 = 41
3. Severe, 7; mild, 25; none, 3; unrecorded, 2 = 37

That is, when recorded in percentages:

1. (Biniodol) severe, 33.3; mild, 35.9; none, 10.3;
unrecorded, 20.5.
2. (Without guaiacol) severe, 12.2; mild, 36.8; none, 39.0;
unrecorded, 12.2.
3. (With guaiacol) severe, 18.9; mild, 67.5; none, 8.1;
unrecorded, 5.5.

The manufacturer of Biniodol supplied the names of several physicians who have used that preparation in their practice. Correspondence with these elicited the following statements:

One had used Biniodol in forty-eight cases and states that “only a few patients complain of pain at all and then only of a general soreness in the muscle.” This physician reports a limited experience with the use of another manufacturer’s “mercury biniodide oil solution” (apparently six cases), but severe pain following the injections made it necessary to abandon that preparation.

Another of these physicians named by the manufacturer, without reference to any series of cases, reports that “Biniodol is superior to any [oily solution of mercury biniodid] that I have tried.”

A third physician has “used it [Biniodol] a few times” and is “convinced that it has no special action or virtue” over “any red mercuric iodide in oil.”

This evidence, in its most favorable estimate, shows Biniodol to be a good 1 per cent. solution of mercuric iodid in oil, but fails to justify attributing to the preparation any unique characteristics. The preparations made in the laboratory were as satisfactory, or better than the Biniodol, and the presence or absence of the guaiacol was of no consequence.

Biniodol conflicts with Rule 6, since claims of superior therapeutic efficiency made for it are not established; and with Rules 8 and 10, since it is an unessential modification of an established nonproprietary article marketed under a proprietary name.

In view of the foregoing, the referee recommends that Biniodol be not accepted for New and Nonofficial Remedies, and that this report, including the clinical investigations of Drs. Cole and Keidel, be authorized for publication.

COMPARATIVE SYMPTOMS RESULTING FROM THE USE OF SEVERAL OILY
SUSPENSIONS OF RED MERCURIC IODID (MERCURY BINIODID)

Report of Dr. H. N. Cole[C]

[C] From the Department of Dermatology and Syphilology of the Western Reserve University and of the Cleveland City Hospital.

At the request of Prof. Torald Sollmann of the Council on Pharmacy and Chemistry of the American Medical Association, we made a comparative study of several oily preparations of red mercuric iodid for intramuscular injections in syphilis.

The information, concerning the preparations submitted to the investigators, was as follows:

OILY SOLUTION OF RED MERCURIC IODID

“It is desired to ascertain whether there is any difference between three preparations, each containing 1 per cent. of mercuric iodid, as to pain, discomfort, induration, etc. The preparations will be labeled “1,” “2” and “3.” They will be sterile.

“One of these preparations will be a plain solution in oil; another will contain, in addition, 2.5 per cent. of guaiacol; the third will be a proprietary preparation containing the guaiacol.

“It is also desirable to know how the oily solution compares with the plain watery solution; but this is of secondary importance.”

The preparations all had the same appearance. The patients were taken indiscriminately, and we attempted to keep them on the injections as long as possible, in order to compare symptoms. Owing, however, to discharge from hospital, symptoms of mercury intoxication, etc., we were unable in all cases to give a thorough trial with each preparation.

In all, eleven patients were treated and seventy-one injections given--by which time our experimental supply was exhausted.

In each case the drug was given intramuscularly in the buttocks and the patients carefully observed for subjective symptoms of pain and for objective symptoms of swelling, induration, abscess formation, etc. The details are given in Table 1.

As will be noted, in several of the cases the patients were more or less confused and gave rather indefinite and conflicting answers. In attempting to compare the results from the different drugs, by careful tabulation one finds that symptoms were more marked with the respective sample as follows:

Preparation 1 was worse than Preparation 2 or 3 in six cases.

Preparation 2 was worse than Preparation 1 in two cases.

Preparation 2 was worse than Preparation 3 in five cases.

Preparation 3 was worse than Preparations 2 or 1 in one case.

TABLE 1.--DETAILS OF INVESTIGATION BY DR. COLE*
====+===+===+============+=======+======+===============+==============
| | | | | | Symptoms
| | | |Prepar-|Dose, +---------------+--------------
Case|Age|Sex| Date | ation | Grain| Induration-- | Objective
| | † | | | | Pain |
| | | | | | |
----+---+---+------------+-------+------+---------------+--------------
1 | 25| ♂ | 6/11/16 | 2 | 1/5 |None |Still painful
| | | 6/12/16 | 1 | 1/4 |None |None
| | | 6/13/16 | 2 | 1/5 |None |Quite painful
| | | 6/14/16 | 2 | 1/4 |Hurt for some |Very tender
| | | | | | time |
| | | 6/16/16 | 2 | 1/5 |Hurt for some |Very tender
| | | | | | time |
| | | 6/17/16 | 3 | 1/5 |Not so painful |Less tender
| | | | | | | than with
| | | | | | | Prepar-
| | | | | | | ation 2.
| | | 6/18/16 | 3 | 1/5 |Not so painful | Can sit on
| | |Discontinued| | | | area; as
| | |(salivation)| | | | needle prick
| | | | | | | is only place
| | | | | | | that it hurts
| | | 6/22/16 | 2 | 1/4 |Hurt, but not |Slight indur-
| | | | | | so long | ation and
| | | | | | | slight
| | | | | | | tenderness
| | | 6/24/16 | 2 | 1/4 |Hurt, but not |Pain “dead
| | | | | | so long | stinging”
| | | | | | | lasts 1 hour
| | | 6/25/16 | 1 | 1/4 |Not so bad |About the same
----+---+---+------------+-------+------+---------------+--------------
2 | 32| ♂ | 6/24/16 | 2 | 1/4 |Some pain |No induration
| | | 6/25/16 | 1 | 1/4 |More pain |Slight indur-
| | | | | | | ation
----+---+---+------------+-------+------+---------------+--------------
3 | ..| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |Painful
| | | 6/13/16 | 2 | 1/4 |No symptoms |Painful
| | | 6/14/16 | 2 | 1/4 |Says the last |Painful
| | | 6/16/16 |Arseno-| | two have hurt |
| | | |benzol | | the more |
| | | 6/17/16 | 3 | 1/5 |More pain than |Small painful
| | | | | | previously | area
| | | 6/17/16 | 3 | 1/5 | |
| | | 6/18/16 | 3 | 1/5 |Not so much |Some indur-
| | | | | | pain: in | ation at site
| | | 6/19/16 | 3 | 1/5 | fact, patient | of injections
| | | 6/20/16 | 3 | 1/4 | says he is |
| | | 6/21/16 | 3 | 1/4 | over it in a |
| | | | | | very short |
| | | | | | while; com- |
| | | | | | plained of |
| | | | | | last one |
| | | 6/22/16 | 2 | 1/4 |Some pain |Considerable
| | | | | | | tenderness
| | | 6/24/16 | 2 | 1/4 |Not so much as | now after so
| | | | | | previously | many injec-
| | | 6/25/16 | 1 | 1/4 | | tions
----+---+---+------------+-------+------+---------------+--------------
4 | 36| ♂ | 6/22/16 | 2 | 1/4 |No pain |No tenderness
| | | 6/24/16 | 2 | 1/4 |Some pain |Some tender-
| | | | | | | ness
| | | 6/25/16 | 1 | 1/4 |Could not sleep|Some tender-
| | | | | | at night | ness; slight
| | | | | | | induration
----+---+---+------------+-------+------+---------------+--------------
5 | 32| ♂ | 6/20/16 | 3 | 20 |Some pain |No induration
| | | | |minims| |
| | | 6/21/16 | 3 | 25 |Some pain |
| | | | |minims| |
| | | 6/23/16 | 2 | 1/4 |Worse pain |No induration
| | | 6/24/16 | 2 | 1/4 |Worse pain |
| | | 6/25/16 | 1 | 1/4 |Worse than any |Slight tender-
| | | | | | |ness
----+---+---+------------+-------+------+---------------+--------------
6 | 20| ♂ | 6/ 8/16 | 1 | 1/6 |Very little |
| | | 6/10/16 | 1 | 1/5 |Very little |
| | | 6/13/16 | 1 | 1/4 |Very little |
| | | 6/14/16 | 2 | 1/4 |Bothered more |
| | | | | | than others |
| | | 6/17/16 | 2 | 1/5 |Quite a little |Still some
| | | | | | pain | soreness
| | | 6/18/16 | 2 | 1/5 |Quite a little |Still some
| | | | | | pain | soreness
| | | 6/19/16 | 3 | 1/4 |Considerably |Very little
| | | | | | less pain than| tenderness
| | | 6/20/16 | 3 | 1/4 | with Prepar- |
| | | 6/21/16 | 3 | 1/4 | ation 2 |
----+---+---+------------+-------+------+---------------+--------------
7 | 30| ♂ | 6/12/16 | 1 | 1/5 |Little pain |None
| | | 6/13/16 | 2 | 1/4 |No pain |
| | | 6/14/16 | 2 | 1/5 |Some pain |
| | | 6/16/16 |Arseno-| | |
| | | |benzol | | |
| | | 6/17/16 | 3 | 1/5 |Not so much |No tenderness
| | | 6/18/16 | 3 | 1/5 |Not so much |No tenderness
| | | 6/19/16 | 3 | 1/5 |Very little |Only slight
| | | | | | pain | amount of
| | | 6/20/16 | 3 | 1/4 | | induration
| | | 6/21/16 | 3 | 1/4 | |
| | | 6/22/16 | 2 | 1/4 |Some pain |Some little
| | | | | | | induration
| | | 6/24/16 | 2 | 1/4 |Considerable |Some indura-
| | | | | | pain | tion
| | | 6/25/16 | 1 | 1/4 |“Fine” |Slight indura-
| | | | | | | tion
----+---+---+------------+-------+------+---------------+--------------
8 | 28| ♂ | 6/13/16 | 2 | 1/5 |Little pain |Little pain
| | | | | | | afterward
| | | 6/15/16 | 2 | 1/5 |Little pain |Little pain
| | | | | | | afterward
----+---+---+------------+-------+------+---------------+--------------
9 | 28| ♀ | 6/17/16 | 2 | 1/5 |Some complaint |Very little
| | | | | | of pain. | induration
| | | 6/18/16 | 2 | 1/5 | Fairly severe |
| | | 6/19/16 | 3 | 1/5 |Some pain; says|Very slight
| | | | | | these have | induration
| | | 6/20/16 | 3 | 1/4 | hurt very much|
| | | 6/21/16 | 3 | 1/4 | less than |
| | | | | | others |
----+---+---+------------+-------+------+---------------+--------------
10 | 37| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |None
| | | 6/13/16 | 1 | 1/4 |No symptoms |None
| | | 6/14/16 | 1 | 1/5 |No symptoms |None
| | | 6/15/16 | 3 | 1/5 |No symptoms |None
| | | 6/16/16 |Arseno-| | |
| | | |benzol | | |
| | | 6/17/16 | 3 | 1/5 |“Much less pain|None
| | | | | | than biniodid |
| | | | | | or grey oil” |
| | | 6/18/16 | 3 | 1/5 |No complaint |None
| | | 6/19/16 | 3 | 1/5 |Says he is over|Some indura-
| | | 6/20/16 | 3 | 1/4 | it in one hour| tion at site
| | | 6/21/16 | 3 | 1/4 | | of injection
----+---+---+------------+-------+------+---------------+--------------
11 | 30| ♀ | 6/11/16 | 1 | 20 |Considerable; |Considerable
| | | | |minims| not so much | pain and
| | | 6/12/16 | 2 | 20 | | tenderness on
| | | | |minims| | palpation
| | | | | | | over area
| | | 6/13/16 | 1 | 25 |Not much pain |Indurated area
| | | | |minims| | at pt. of
| | | | | | | each.
| | | | | | | Painful
| | | 6/14/16 | 1 | 25 |Not much pain |Slight indura-
| | | | |minims| | tion
----+---+---+------------+-------+------+---------------+--------------

* The diagnosis in Case 5 was primary syphilis, and in the other cases,
secondary syphilis.

† In this column, ♂ indicates male, and ♀ female. In no case did
Wassermann become negative.

The criticism may be raised that the number of cases and of injections is too small to permit the drawing of any just conclusions. Even should we grant it, the statistics certainly do not prove any marked superiority of any one of the preparations over the others. We wish to thank Dr. Sollmann for advising and directing us in this work, and Drs. Bailey, Bernstein, Markus and Reycraft for assistance in carrying it out.

Report of Dr. Albert Keidel

Twenty cases were chosen at random from the syphilitic patients attending the clinic. They were given intramuscular injections of the three solutions, in amounts varying from 1 to 2 c.c., at intervals (in most instances) of two days. The injections were invariably made into the gluteal muscles, at depths of from 2 to 2-1/2 inches, and ordinary care exercised to preserve asepsis. After injection the patient was allowed to depart, and the result was recorded at the succeeding visit. The result was determined from the patient’s statement and our examination. Some patients received injections of only one solution; some were treated with first one and later with another, and one patient received all three at different times. The solutions were never mixed for a single injection, of course.

TABLE 2.--REACTIONS IN TWENTY CASES REPORTED BY DR. KEIDEL

==================================================================
Preparation Reactions Number of
┌────────────┴────────────┐ Injections
Severe Mild None Undetermined
1 13 14 4 8 39
2 5 15 16 5 41
3 7 25 3 2 37
---
117
------------------------------------------------------------------

The solutions are understood to contain a 1 per cent. solution of red mercuric iodid in oil, two of them containing in addition 2.5 per cent. of guaiacol, one of these being a proprietary preparation. The solutions are designated as Preparations 1, 2 and 3, respectively, corresponding to the numbers on the labels of the bottles in which they were originally received. The local reactions are recorded as “severe” (S), “mild” (M), “none” (O) and “Undetermined” (U). By “severe” is meant very severe pain lasting for from several hours to several days; by “mild” is meant slight pain or numbness for several hours, or less than an hour; “none” indicates that there was no local reaction, and “undetermined,” that the patient has failed to return after the last injection.

In Table 3 all the details of the investigation are recorded. Under “Local Reaction,” the letters represent the type of reaction after each injection, in the order in which they were given; when two solutions were used in the same case, the letters represent the reactions following the solution opposite which they stand. In the fifth column the plus and minus symbols indicate the Wassermann reaction; plus indicates a completely positive, and minus a completely negative reaction. When there is only one sign, it refers to the reaction at the end of treatment; when there are two, to the reaction before and after. The seventh column shows the clinical result at the end of treatment; when no note is made, it means that there was no change noted. In the eighth column are noted any objective results observed at the time of examinations of the patients.

The injections were made and the result charted by Dr. E. L. Zimmermann, of my staff, under my directions and supervision.--(_Abstracted in The Journal A. M. A., Feb. 24, 1917._)

TABLE 3.--DETAILS OF INVESTIGATION BY DR. KEIDEL

====+===+=======+=========+========+======+=======+==========+==========+============
| | | | Total |Dura- |Effect | | |
Case|No.|Prepar-| Local | Amount | tion | on | Type of | Result | General
| | ation |Reaction |Solution| of |Wasser-| Case | | Remarks
| | | | Given, |Treat-| mann | | |
| | | | C.c. | ment | | | |
----+---+-------+---------+--------+------+-------+----------+----------+------------
1 | 3 | 2 | OOO | 3 | 6 da.| + |Latent | |
2 | 5 | 2 | MOSMS | 5.6 | 9 da.| + |Gummas....|Marked |
3 | 7 | 1 | MMM; | 9.5 | 3 mo.|- to + |Latent | improve- |
| | | others U| | | | | ment |
| 3 | 2 | UUU | | | | | |
4 | 1 | 2 | U | 0.75 | ... | + |Latent | |
5 | 4 | 1 | SSSM | 4.4 | 9 da.| - |Gummas....|..........|After 4th
| | | | | | | | | injection,
| | | | | | | | | developed
| | | | | | | | | diarrhea;
| | | | | | | | | melena
6 | 9 | 1 |OOUMSOSMU| 9.1 | 1 mo.| - |Latent | |
7 | 2 | 3 | MM | 3.8 | 2 da.| + |Latent |..........|Well
| | | | | | | | | tolerated
8 | 7 | 2 | OOOOMOU | 9.6 |17 da.|+ to + |Primary...|Primary |
| | | | | | | | healed |
9 | 4 | 1 | SMMU | 5.5 | 9 da.| |Gumma.....|Improved |
10 | 3 | 3 | MSS | 3 | 6 da.| + |Palmar |Markedly |
| | | | | | | syphilis;| improved |
| | | | | | | tertiary | |
11 | 7 | 3 | MSMMMMM | 10.6 |13 da.|+ to + |Latent | |
12 | 3 | 2 | MMO | 5.4 |14 da.| + |Secondary |Rash |Developed
| 2 | 1 | SM | | | | (papular)| disap- | toxic ery-
| | | | | | | | pearing.| thema on
| | | | | | | | | thighs.
| | | | | | | | | Cleared up
| | | | | | | | | on stopping
| | | | | | | | | HgCl₂ and
| | | | | | | | | under local
| | | | | | | | | treatment
13 |10 | 3 | MMMMMMMM| 12.6 |20 da.|+ to + |Secondary |Rash |Small
| | | MMU | | | | (lichen | not | induration
| | | | | | | syph.) | improved.| following
| | | | | | | | | injection
| | | | | | | | | of 1.2 c.c.
14 | 6 | 2 | OOMSMM | 7.2 |17 da.|+ to + |Old |..........|Responded to
| 2 | 1 | SM | | | | cerebro- | | doses of
| | | | | | | spinal | | 1 c.c. with
| | | | | | | syphilis | | salivation;
| | | | | | | | | fever after
| | | | | | | | | injection
| | | | | | | | | of 1.2 c.c.
15 | 4 | 1 | SOMS | 4.2 | 7 da.|+ to + |Secondary |No |
| | | | | | | (condyl- | improve- |
| | | | | | | omas) | ment |
16 | 9 | 3 |OMOMMSMSO| 10.4 |12 da.| + |Secondary |Pustules |Slight
| 2 | 2 | SO | | | | (pustular| dried up;| gingivitis
| | | | | | | syph.) | headache | following
| | | | | | | | and fever| dose of
| | | | | | | | gone | 1.5 c.c.
17 | 5 | 1 | SSMSU | 13.3 |18 da.|+ to + |Tertiary; |General |
| 2 | 2 | MS | | | | aortitis.| condition|
| 2 | 3 | MS | | | | | improved |
18 | 4 | 2 | OOMM | 9.5 |13 da.|- to + |Latent | |
| 2 | 1 | MM | | | | |Markedly |
| | | | | | | | improved |
19 | 2 | 3 | MU | 2.5 | 5 da.| + |Gumma.....| |
20 | 5 | 2 | MMMMO | 9 |14 da.|+ to + |Latent....|Marked |Small
| 2 | 3 | MS | | | | | general | induration
| | | | | | | | improve- | following
| | | | | | | | ment | No. 3
----+---+-------+---------+--------+------+-------+----------+----------+------------

CORPORA LUTEA (SOLUBLE EXTRACT), PARKE, DAVIS & CO.

Report of the Council on Pharmacy and Chemistry

Following inquiries, the Council took up for consideration “Corpora Lutea (Soluble Extract),” marketed by Parke, Davis & Co. in the form of ampules and proposed for hypodermic administration. The report which appears below was submitted to the Council by a committee, and was adopted by the Council. Corpora Lutea (Soluble Extract) was declared inadmissible to New and Nonofficial Remedies, and publication of the report authorized.

W. A. Puckner, Secretary.

Corpora Lutea (Soluble Extract) has not been submitted by the manufacturer. The information of the referee is based, therefore, on the claims made in the trade package, and on the statements in the price list. These show that the product is essentially secret and claims made for the actions and uses of the preparation do not make clear the essentially experimental status of the article, and are therefore misleading.

_Conflict with Rule 1._--No definite statement of composition appears beyond the indefinite claim that it is an aqueous solution of “soluble Corpora Lutea Extract,” each ampule corresponding to 0.2 Gm. of desiccated gland. How these soluble products are obtained, whether they represent _all_ the water-soluble principles, or whether some have been eliminated, are questions that are not answered. Yet such information is essential to intelligent and scientific use, for, as there is no method of standardization, the method of preparation is the only mark of identity. For instance, we do not know at this time whether proteins have anything to do with the supposed value of corpora lutea. It is, therefore, essential to know whether or not the proteins have been eliminated.

_Conflict with Rule 6._--The circular in the package advises the hypodermic use of this extract, not only in functional amenorrhea and the ordinary reflex consequences of physiologic or artificial menopause, but also in:

“‘neurasthenic’ symptoms during menstrual life”;

“sterility, not due to pyogenic infection or mechanical
obstruction”;

“repeated abortions, not due to disease or mechanical factors”;

“hyperemesis in the early months of pregnancy.”

These are not stated merely as conditions in which various enthusiasts have tried corpus luteum, but as conditions “for which it will be found serviceable.”

It is not necessary to inform the medical profession that this statement is calculated to raise expectations which cannot possibly be fulfilled. Even the manufacturers seem to realize this; at least they speak somewhat indefinitely of “suitable cases,” “good judgment,” “real indications,” etc. But they proceed to nullify this warning--if it was intended as a warning--by their illustrations of unsuitable cases, for instance, “amenorrhea due to extreme anemia, dysmenorrhea due to cervical stenosis,” etc. Finally, they sum up the case:

“Therefore, additional emphasis on the necessity for the proper
selection of cases is essential in order that this useful
preparation may not be unjustly discredited.”

How these cases of sterility, abortions, etc., are to be selected is not revealed. In other words, the restriction is no more than a convenient device by which every improvement is to be attributed to the medicine, and every failure to the physician.

The referee recommends that Corpora Lutea (Soluble Extract), Parke, Davis & Co., be held ineligible to N. N. R., because it is a secret preparation advertised under extravagant claims.

[Editorial Comment.--Was it not in Weir Mitchell’s “Adventures of François” that the itinerant promised to pull teeth without any pain, _if the patient would hold absolutely still_? And, _mirabile dictu_, the ones who suffered were those who had not held absolutely still!]--(_From The Journal A. M. A., April 7, 1917._)

WHEELER’S TISSUE PHOSPHATES

Report of the Council on Pharmacy and Chemistry

The Council held that the contribution from the A. M. A. Chemical Laboratory, “Wheeler’s Tissue Phosphates,” demonstrates that this is a semisecret, complex and irrational preparation, sold with misleading claims concerning its medicinal constituents and therapeutic properties.

The Council directed that the report be included with the Annual Council Reports and declared Wheeler’s Tissue Phosphates in conflict with Rules 1, 6, 8 and 10.

W. A. Puckner, Secretary.

WHEELER’S TISSUE PHOSPHATES

L. E. Warren, Ph.C., B.S.

“Wheeler’s Tissue Phosphates,” known also as “Compound Elixir of Phosphates and Calisaya,” is advertised as a nerve food and a nutritive tonic. The label states that it contains calcium, iron, sodium trihydrogen phosphates, alkaloids of Peruvian bark with 12-1/2 per cent. of alcohol. The preparation is sold by the T. B. Wheeler, M. D. Co., of Rouses Point, New York. According to the manufacturer, Wheeler’s Tissue Phosphates

“... is an _inorganic_ combination of the phosphates of iron and
calcium and hydrogen (phosphoric acid) together with hydrochloric
acid, hydrocyanic acid, and quinine, cheerful coloring, and a
delicious, cordial-like flavoring.”

“... The iron is the green, inorganic phosphate and the calcium the
simple white phosphate of your early student days....”

The preparation is a red liquid, having an acid reaction, a sweet-bitter taste and the odor of wild cherry. Qualitative tests indicated the presence of calcium, iron, a phosphate, a chlorid, a sulphate, quinin or cinchona alkaloids, alcohol, sodium, cochineal coloring and invert sugar. Ammonium salts, glycerol, citrates or lactates were not found. From the quantitative values obtained the preparation may be taken to represent:

Sp. gr at 25C./25C. 1.1087
Alcohol (per cent, by volume) 11.35

Gm. per 100 c.c.
Calcium phosphate [Ca₃(PO₄)₂]*  0.397
Iron phosphate (FePO₄.4H₂O)* 0.068
Chlorid (as hydrochloric acid) 0.407
Sodium sulphate (Na₂SO₄.10H₂O)  0.043
Quinin sulphate (U. S. P.) 0.041
Sodium phosphate (Na₂HPO₄.12H₂O)  0.065
Invert sugar 26.824
Water, cochineal and flavor, to make 100 c.c.

* It should be understood that the calcium and iron salts are held in
solution by the hydrochloric acid.

The dose of Wheeler’s Tissue Phosphates recommended by the manufacturer is a tablespoonful or about 15 c.c. (1/2 oz.). The total calcium in a dose of the preparation is equivalent to about one-sixth of an average dose of the official calcium chlorid, and the total phosphate to each dose is equivalent to about one-fourth of a dose of the official diluted phosphoric acid. Each prescribed dose of the preparation contains about 0.01 gm. (2/13 grain) of iron phosphate or about one twenty-fifth of the average dose, and to obtain a Pharmacopeial dose of iron phosphate the patient would be obliged to take three-fourths of the contents of an entire bottle--or 12 ounces--of the preparation. If it be assumed that all of the chlorid present is in the form of free hydrochloric acid, each dose of the preparation contains the equivalent of about two-thirds of one Pharmacopeial dose of diluted hydrochloric acid. Each dose of the preparation contains about 0.0062 gm. (1/10 grain) of quinin sulphate, or about one-sixteenth of the average tonic dose. In other words, to obtain the amount of quinin sulphate given in the U. S. Pharmacopeia as the tonic dose, the patient would be required to swallow 7-1/2 fluidounces of the proprietary preparation, or the contents of nearly half a bottle. The fallacy of prescribing Wheeler’s Tissue Phosphates either for its quinin or its iron content is apparent.

Wheeler’s Tissue Phosphates is, then, a mildly bitter flavored syrup which contains nearly 12 per cent. of alcohol, small quantities each of calcium phosphate and hydrochloric acid and insignificant amounts of iron and quinin salts. In other words, essentially it is a sweetened solution of small quantities of calcium phosphate in very dilute hydrochlorid acid together with 12 per cent. of alcohol.

Bearing in mind the analysis of the preparation, how ludicrous some of the claims appear:

“_Tissue Phosphates_ is not a hypophosphite preparation; it is
not a combination of glycerophosphates or other organic salts, or
so-called peptonates and manganates, all recently condemned by
the best therapeutic opinion here and in Europe, as much slower
and less active than the simpler salts. The iron is the green,
inorganic phosphite and the calcium the simple white phosphate of
your early student days. Nature takes these simple salts and builds
them rapidly into lecithin, bone, and other tissue, without the
delay incurred by splitting up the organic salts before she can
recombine them.”

“Tissue phosphates is in fact a _chemical food_.”

“The formula, suggested by Professor Dusart, of Paris, combines in
an easily assimilable and agreeable cordial; medium medicinal doses
of Phosphorus, the Generator of Nerve Force; Calcium Phosphate,
for Cell Development and Nutrition; Sodium Phosphate, a stimulant
of Liver and Pancreas and Corrective of Acid Fermentation in the
Alimentary Canal; Iron, generating in the Blood, Heat and Motion,
Phosphoric Acid, Tonic in Sexual Debility; Alkaloids of Calisaya,
Antimalarial and Antipyretic; Extract of Wild Cherry, Tonic, yet
Calming Irritation and Diminishing Nervous Excitement; Ethyl
Alcohol 12.5%; and Aromatics.”

Although the claim is made that the “formula” of Wheeler’s Tissue Phosphates has been “suggested by Professor Dusart,” such of Dusart’s papers as were available in this country[111] failed to disclose any “formula” that was at all comparable to this product.

[111] Dusart, L.: Recherches expérimentales sur le rôle physiologique et thérapeutique du phosphate de chaux, Paris, 1870; Quel est l’acide du suc gastrique? Lille, 1874, unbound, 8 pages; Notice sur l’emploi et les proprietés du lacto-phosphate de chaux, Clichy, 1868, unbound, 8 pages. Dusart and Blache: Recherches sur l’assimilation du phosphate de chaux, Paris, 1868, unbound, 15 pages.

[Editorial Note.--The investigation verifies facts that must be obvious to every physician who has given the matter thought. “Wheeler’s Tissue Phosphates” is an unscientific, shotgun mixture whose most active and powerful drug is the alcohol it contains. That it was not years ago relegated to the realms of obsolete and discarded preparations is a commentary alike on the lack of scientific discrimination and the persuasive power of advertising. While in the past “Wheeler’s Tissue Phosphates” has been advertised extensively in medical journals, it seems that now the chief, if not the only beneficiary of the advertising appropriation for this product is the _New York Medical Journal_, which weekly heralds the “Delicious” and “Sustaining” qualities of “The Ideal Tonic for Fastidious Convalescents.”]--(_From The Journal A. M. A., May 5, 1917._)

THE CLAIMED GALACTAGOGUE EFFECTS OF NUTROLACTIS
AND GOAT’S RUE NOT SUBSTANTIATED

Report of the Council on Pharmacy and Chemistry

Specific lactagogues--drugs which stimulate the secretion of milk--are unknown to science. Yet medical publications give space to advertisements of a proprietary--“Nutrolactis”--which is said to increase the milk supply of nursing mothers. Since dependence on a preparation of this kind is likely to cause neglect of the only means of increasing a scanty milk supply of nursing mothers--care of the general health and a sufficient quantity of proper food--this proprietary and the drug “goat’s rue,” (_Galega officinalis_) which the proprietors hint as being the potent constituent, were subjected to a critical study to determine their possible influence on milk secretion. For this purpose the Council secured the help of A. J. Carlson, Ph.D., professor of physiology, University of Chicago. Dr. Carlson, with the aid of A. Woelfel, M.D., and Marian Lewis, Sc.M., undertook to estimate the effect of Nutrolactis and of goat’s rue on nursing dogs and goats with the intention of extending the study to nursing mothers if the animal experiments so warranted. The contribution, “The Alleged Galactagogue Action of Galega and Nutrolactis,” by Marian Lewis and A. J. Carlson from the Hull Physiological Laboratory of the University of Chicago, which appears below, shows that Nutrolactis and goat’s rue are without influence on the milk secretion in nursing animals.

The Council endorsed the work of Lewis and Carlson and held that the claimed galactagogue effects of Nutrolactis and goat’s rue are not substantiated.

W. A. Puckner, Secretary.

THE ALLEGED GALACTAGOGUE ACTION OF GALEGA AND NUTROLACTIS[D]

Marian Lewis, Sc.M., and A. J. Carlson, Ph.D.

CHICAGO

[D] From the Hull Physiological Laboratory of the University of Chicago.

[D] This investigation was begun in 1915 by Drs. A. Woelfel and A. J. Carlson.

It is well established that the food best adapted to the energy and growth requirements of the infant is normal mother’s milk. Any decrease in quantity or deterioration in quality of the maternal secretion is soon followed by a parallel impairment of growth, loss of weight, or lowered resistance to infection in the infant. The widespread occurrence of deficient milk secretion is a matter of common knowledge. The discovery of true lactagogues, or specific substances which increase the quantity and quality of the milk on being administered to nursing mothers, would therefore be of very great importance. In view of this great medical and economic interest in true lactagogues it is not surprising to find that the medical and biologic literature records discoveries of lactagogues based on hope rather than demonstration, and that spurious lactagogues are on the market.

Some of the factors known to affect milk secretion are general health, food supply, psychic state, and heredity. The mechanism of secretion and the method by which these factors affect it are imperfectly understood. In general it has been observed that milk yield improves both in quantity and in quality with improvement in general health, better food supply, and more favorable psychic state. The influence of heredity is taken advantage of by dairymen who are well acquainted with the potential milk production of the different breeds of cattle.

Among the substances which have been reported to stimulate milk secretion may be mentioned the extract of the posterior lobe of the hypophysis. But pituitary extract is not a true lactagogue, because its action is confined to the smooth musculature of the gland ducts, causing a more or less complete ejection of the milk already formed; it has no effect on the gland cells or the actual secretory process in the direction of increasing the milk yield. Extracts of thymus, corpus luteum, ovaries, uterus, placenta, fetus, and the mammary gland itself have also been reported to have a temporary stimulating effect on the quantity of milk secreted, but when these extracts are given by mouth they are apparently without specific influence on the mammary gland.

Galega, or goat’s rue (_Galega officinalis_), is an herb described in the National Formulary as being slightly bitter and astringent. In 1873, Gillet-Damotti,[112] in a communication to the French Academy, stated that this plant when fed to cows increases the secretion of milk from 35 to 50 per cent. Other French writers have affirmed that goat’s rue is a lactagogue. In Germany, Fragner[113] made a preparation called Galegal, using galega as the active principle and combining it with lactose to give it a pleasant taste and make it soluble in water, milk, coffee, and tea. This preparation was reported on favorably by Scherer,[114] who asserts that he obtained positive results in fifty-four of the eighty cases in which he used it.

[112] Gillet-Damotti: Comp. rend. Acad. d. Sc., July 7, 1873.

[113] Fragner: Wien. med. Wchnschr. =60=:1033-1036, 1910.

[114] Scherer: Wien. med. Wchnschr. =60=:1033-1036, 1910.

More recently Huët[115] tested the effects of Theinhardt’s Hygiama lactogene on four lactating women. This preparation is said to be composed of hygiama,[116] galega and anise. Analysis showed that it contains albumins, fat, soluble and insoluble carbohydrates, salts and water. Huët could not observe any influence from the use of this preparation, either on the quantity or on the composition of the milk secreted.

[115] Huët: Nederlandsch Tijdschr. v. Geneesk. =1=:1353-1370, 1914.

[116] Hygiama is said to be a food consisting of condensed milk, with (fatless) cocoa and cereals added to it (Encyclopedia and Dictionary of Medicine and Surgery, 1907).

Nutrolactis[117] is a commercial preparation sold by the Nutrolactis Company of New York at $1 a bottle. The label states that it contains 5 per cent. of alcohol; that it contains fluid extracts of the family of “galactagogic plants,” and that it is intended to “increase the supply of mother’s milk.” It is recommended to maintain “quality and quantity until the end of normal lactation.” Nutrolactis is also recommended for a mother debilitated by lactation. It is claimed that “Nutrolactis does not _force_ the secretion of milk but merely assists such secretion.” Years ago Millbank[118] reported good results from the use of Nutrolactis. After more than a year’s use he concluded that it was more satisfactory than any other lactagogue hitherto employed by him, which is not saying very much, as specific lactagogues are as yet unknown. Nutrolactis is still (1916) extensively advertised in various medical journals as a lactagogue.