Volume 1 / Part 1 — FOREWORD (continued 5)
Reading edition
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*
CaseAgeSex†DatePrepara- tionDose, GrainSymptoms
Induration—PainObjective
125♂M6/11/1621⁄5NoneStill painful
6/12/1611⁄4NoneNone
6/13/1621⁄5NoneQuite painful
6/14/1621⁄4Hurt for some timeVery tender
6/16/1621⁄5Hurt for some timeVery tender
6/17/1631⁄5Not so painfulLess tender than with Preparation 2. Can sit on area; as needle prick is only place that it hurts
6/18/1631⁄5Not so painful
Discontinued (salivation)
6/22/1621⁄4Hurt, but not so longSlight induration and slight tenderness
6/24/1621⁄4Hurt, but not so longPain “dead stinging” lasts 1 hour
6/25/1611⁄4Not so badAbout the same
232♂M6/24/1621⁄4Some painNo induration
6/25/1611⁄4More painSlight induration
3..♂M6/12/1611⁄5No symptomsPainful
6/13/1621⁄4No symptomsPainful
6/14/1621⁄4Says the last two have hurt the morePainful
6/16/16Arseno- benzol
6/17/1631⁄5More pain than previouslySmall painful area
6/17/1631⁄5
6/18/1631⁄5Not so much pain: in fact, patient says he is over it in a very short while; complained of last oneSome induration at site of injections
6/19/1631⁄5
6/20/1631⁄4
6/21/1631⁄4
6/22/1621⁄4Some painConsiderable tenderness now after so many injections
6/24/1621⁄4Not so much as previously
6/25/1611⁄4
436♂M6/22/1621⁄4No painNo tenderness
6/24/1621⁄4Some painSome tenderness
6/25/1611⁄4Could not sleep at nightSome tenderness; slight induration
532♂M6/20/16320 minimsSome painNo induration
6/21/16325 minimsSome pain
6/23/1621⁄4Worse painNo induration
6/24/1621⁄4Worse pain
6/25/1611⁄4Worse than anySlight tenderness
620♂M6/ 8/1611⁄6Very little
6/10/1611⁄5Very little
6/13/1611⁄4Very little
6/14/1621⁄4Bothered more than others
6/17/1621⁄5Quite a little painStill some soreness
6/18/1621⁄5Quite a little painStill some soreness
6/19/1631⁄4Considerably less pain than with Preparation 2Very little tenderness
6/20/1631⁄4
6/21/1631⁄4
730♂M6/12/1611⁄5Little painNone
6/13/1621⁄4No pain
6/14/1621⁄5Some pain
6/16/16Arseno- benzol
6/17/1631⁄5Not so muchNo tenderness
6/18/1631⁄5Not so muchNo tenderness
6/19/1631⁄5Very little painOnly slight amount of induration
6/20/1631⁄4
6/21/1631⁄4
6/22/1621⁄4Some painSome little induration
6/24/1621⁄4Considerable painSome induration
6/25/1611⁄4“Fine”Slight induration
828♂MM6/13/1621⁄5Little painLittle pain afterward
6/15/1621⁄5Little painLittle pain afterward
928♀M6/17/1621⁄5Some complaint of pain. Fairly severeVery little induration
6/18/1621⁄5
6/19/1631⁄5Some pain; says these have hurt very much less than othersVery slight induration
6/20/1631⁄4
6/21/1631⁄4
1037♂M6/12/1611⁄5No symptomsNone
6/13/1611⁄4No symptomsNone
6/14/1611⁄5No symptomsNone
6/15/1631⁄5No symptomsNone
6/16/16Arseno- benzol
6/17/1631⁄5“Much less pain than biniodid or grey oil”None
6/18/1631⁄5No complaintNone
6/19/1631⁄5Says he is over it in one hourSome induration at site of injection
6/20/1631⁄4
6/21/1631⁄4
1130♀M6/11/16120 minimsConsiderable; not so muchConsiderable pain and tenderness on palpation over area
6/12/16220 minims
6/13/16125 minimsNot much painIndurated area at pt. of each. Painful
6/14/16125 minimsNot much painSlight induration
* The diagnosis in Case 5 was primary syphilis, and in the other cases, secondary syphilis.
† In this column, ♂M indicates male, and ♀F 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 21⁄2 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
PreparationReactionsNumber of Injections
SevereMildNoneUndetermined
11314 48 39
2 515165 41
3 725 32 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
CaseNo.Prepar- ationLocal ReactionTotal Amount Solution Given, C.c.Duration of TreatmentEffect on Wasser- mannType of CaseResultGeneral Remarks
132OOO 3 6 da.+Latent
252MOSMS 5.6 9 da.+GummasMarked improvement
37 31 2MMM; others U UUU 9.5 3 mo.– to +Latent
412U 0.75 ...+Latent
541SSSM 4.4 9 da.–GummasAfter 4th injection, developed diarrhea; melena
691OOUMSOSMU 9.1 1 mo.–Latent
723MM 3.8 2 da.+LatentWell tolerated
872OOOOMOU 9.617 da.+ to +PrimaryPrimary healed
941SMMU 5.5 9 da.+GummaImproved
1033MSS 3 6 da.+Palmar syphilis; tertiaryMarkedly improved
1173MSMMMMM10.613 da.+ to +Latent
123 22 1MMO SM 5.414 da.+Secondary (papular)Rash disappearingDeveloped toxic erythema on thighs. Cleared up on stopping HgCl2 and under local treatment
13103MMMMMMMM MMU12.620 da.+ to +Secondary (lichen syph.)Rash not improvedSmall induration following injection of 1.2 c.c.
146 22 1OOMSMM SM 7.217 da.+ to +Old cerebro- spinal syphilisResponded to doses of 1 c.c. with salivation; fever after injection of 1.2 c.c.
1541SOMS 4.2 7 da.+ to +Secondary (condylomas)No improvement
169 23 2OMOMMSMSO SO10.412 da.+Secondary (pustular syph.)Pustules dried up; head- ache and fever goneSlight gingivitis following dose of 1.5 c.c.
175 21 2SSMSU MS13.318 da.+ to +Tertiary; aortitisGeneral condition im- proved
23MS
1842OOMM 9.513 da.– to +Latent
21MMMarkedly improved
1923MU 2.5 5 da.+Gumma
205 22 3MMMMO MS 914 da.+ to +LatentMarked general improvementSmall induration following 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 121⁄2 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 sugar26.824
Water, cochineal and flavor, to make100 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 71⁄2 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 country111 failed to disclose any “formula” that was at all comparable to this product.
[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.
Marian Lewis, Sc.M., and A. J. Carlson, Ph.D.
CHICAGO
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, Fragner113 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.
More recently Huët115 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.
Nutrolactis117 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 Millbank118 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.
METHODS OF INVESTIGATION
The alleged lactagogue action of galega and Nutrolactis was tested on lactating dogs and goats. In these animals the psychic factors, or suggestion, are largely eliminated. If the results had been positive or had indicated lactagogue action, the test would have been extended to nursing women. The puppies and kids were weighed before and after nursing and a record kept of the amount of milk obtained at each nursing (the animals nursing from three to five times daily). The mothers were fed with varying doses of the drugs, and the milk yield compared with that of a control period during which no drugs were administered. An effort was made to keep the conditions of the experiments uniform throughout.
The galega was ground and mixed with the food. The Nutrolactis was mixed with food given by the stomach tube, or in some cases with a spoon. Galega was tested on two goats and Nutrolactis on one goat and nine dogs. The results are given herewith:
GALEGA
Goat 1: Control period, 1,600 gm., milk av. daily yield for 7 days. Galega period (30 gm. galega mixed with oats), 860 gm., milk av. daily yield for 8 days. Kids weaned at end of period.
Goat 2: Control period, 1,161 gm. milk av. daily yield for 9 days. Galega period (30 gm. galega mixed with oats), 860 gm. milk av. daily yield for 8 days. (25 gm. galega in same way), 810 gm. milk av. daily yield for 10 days. Control period, 896 gm. milk av. daily yield for 6 days.
NUTROLACTIS
Goat 3: Control period, 896 gm. milk av. daily yield for 6 days. Nutrolactis period (30 c.c. Nutrolactis mixed with oats), 658 gm. milk av. daily yield for 9 days. Control period, 666 gm. milk av. daily yield for 5 days.
Dog 1: Control period, 176 gm. milk av. daily yield for 7 days. Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 55 gm. milk av. daily yield for 12 days.
Dog 2: Control period, 189 gm. milk av. daily yield for 6 days. Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 72 gm. milk av. daily yield for 11 days.
Dog 3: Control period, 93 gm. milk av. daily yield for 8 days. Nutrolactis period (8 c.c. Nutrolactis on bread), 17 gm. milk av. daily yield for 5 days.
Dog 4: Control period, 28 gm. milk av. daily yield for 7 days. Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 47 gm. milk av. daily yield for 6 days. (10 c.c. Nutrolactis by stomach tube), 43 gm. milk av. daily yield for 8 days. Control period, 41.5 gm. milk av. daily yield for 6 days. Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33.5 gm. milk av. daily yield for 4 days.
Dog 5: Control period, 67 gm. milk av. daily yield for 6 days. Nutrolactis period (10 c.c. Nutrolactis on bread), 81 gm. milk av. daily yield for 6 days.
Dog 6: Control period, 40 gm. milk av. daily yield for 5 days. Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33 gm. milk av. daily yield for 8 days. Control period, 26 gm. milk av. daily yield for 4 days.
Dog 7: Control period, 283 gm. milk av. daily yield for 9 days. Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 155 gm. milk av. daily yield for 15 days. (15 c.c. Nutrolactis by stomach tube), 82 gm. milk av. daily yield for 6 days. Control period, 33 gm. milk av. daily yield for 3 days.
Dog 8: Control period, 238 gm. milk av. daily yield for 8 days. Nutrolactis period (20 c.c. Nutrolactis on bread), 223 gm. milk av. daily yield for 4 days. (20 c.c. Nutrolactis on bread), 46 gm. milk av. daily yield for 6 days.
Dog 9: Control period, 223 gm. milk av. daily yield for 6 days. Nutrolactis period (10 c.c. Nutrolactis on bread), 178 gm. milk av. daily yield for 15 days. (15 c.c. Nutrolactis on bread), 146 gm. milk av. daily yield for 5 days.
COMMENT AND CONCLUSION
Goat 1 had already been lactating for over two months, and the yield was gradually decreasing at the time the observations were begun. The administration of galega did not check this decrease. Goat 2 should have been a very favorable subject, for the kid was about a week old at the time the observations were begun. Both galega and Nutrolactis caused a decrease in milk yield of this animal. This decrease is perhaps partly due to the animal’s distaste for the drugs and her consequent failure to eat as well as during the control periods.
Administration of Nutrolactis was accompanied by an increase in milk in only two animals, Dog 4 and Dog 5. A detailed examination of the records of these two dogs shows that in both cases there was a progressive increase in milk yield during the control period and that administration of the drug failed to accelerate this increase. On the contrary, the curve for Dog 5 takes a sudden drop immediately after the first administration of the drug.
The records of Dogs 6 and 7 show that the yield during the second control period is lower than that of the preceding periods. Although the administration of the drug in both cases was followed by a decrease in the yield, it may be urged that the drug has some lactagogue action, for its discontinuance was followed by a decrease in yield. This effect, however, is also apparent rather than real, for the data show a gradual falling off in yield during the period of administration of the drug, which decrease was not accelerated by withdrawing the drug.
Our data show that galega and Nutrolactis, when taken by mouth, and the elements of suggestion excluded, had no beneficial effect on lactation—at least in so far as the quantity of milk is concerned.—(From The Journal A. M. A., May 26, 1917.)
THE RUSSELL EMULSION AND THE RUSSELL PREPARED GREEN BONE
Report of the Council on Pharmacy and Chemistry
The following report on “The Russell Emulsion” and “The Russell Prepared Green Bone,” marketed by the Standard Emulsion Company, was submitted to the Council by a referee. The Council endorsed the report and authorized its publication.
W. A. Puckner, Secretary.
The Russell Emulsion is put up in a neat package and advertised in an attractive pamphlet, on the cover of which we are told: “Truth Always Justifies The Superlative Degree.” As what follows in the booklet and in the printed circulars certainly does not lack superlatives, this is doubtless a warning.
In addition to the pamphlet and circular advertising, the product seems to be systematically boomed by a lecture scheme in which one Dr. Hague talks before medical societies and distributes advertising matter. The lecture is succeeded by a follow-up letter scheme through which matter is sent to members of the society. Hague ostensibly discusses “lime starvation in tuberculosis,” but medical societies soon learned to estimate his work as essentially to advertise the Russell products. Last April the Medical Society of the State of Pennsylvania sent out a circular letter to its county organizations on the subject of the Russell-Hague propaganda which opens in this way:
“You have doubtless received a letter from Dr. William Grant Hague of New York, offering to address your county society on Tuberculosis. After due investigation, it is respectfully suggested that it may not be desirable to ask him to address your society....”
The statements in the pamphlet and circular published are typical of the whole method of exploitation. For example, can such claims as these be surpassed by the veriest quack?
“Science cannot improve the means employed in producing The Russell Emulsion.”
“Genius has not devised better methods than are used in manufacturing The Russell Emulsion.”
“Money cannot buy better products than are used in The Russell Emulsion.”
“Experience cannot suggest a more nutritious combination of fats than we use in The Russell Emulsion.”
The emulsion is said to be made of equal parts of beef-fat, coconut, peanut and cottonseed oils, held in suspension by albumin. The latter we are told is applied to each globule of the emulsion by an “elaborate technical process” devised by Dr. Russell. The mixture is everywhere spoken of as a “physiological” emulsion, but the word is always in quotation marks. Why it is called “physiological” is not clear, but the term may be counted on to impress the unthinking or the unscientific.
Numerous false and exaggerated statements are made about this “physiological” emulsion with reference to food value. For instance:
“The nutritional value of fats differ; the nutritional value of these fats and their increased efficiency by combination over all others have been determined by extensive clinical observation.”
And also:
“The Russell Emulsion is approximated in food value by no other emulsion or food product in existence.”
“A ‘physiological’ emulsion is a predigested food. It is absorbed with little assistance from the digestive juices, and with no waste of energy. It is, therefore, the ideal food ...”
These are sample statements found in the pamphlet and accompanying circular. A dozen or more pathologic conditions are mentioned in which this “ideal food” is specifically indicated; but we find, also, this curious statement: “Patients can rarely take this dose [speaking of the maximum dose of 2 ounces night and morning] for more than three or four weeks without showing symptoms of over-feeding.” This unguarded remark about an ingestion of 48 grams of fat daily prompts one to ask what is wrong with the “ideal predigested food.”
Russell is wedded to the idea that “lime starvation” is the main factor in tuberculosis, and insists on the importance of large amounts of fat for the “lime starved.”
“Dr. Russell was the original interpreter of the Lime Starved State and originated The Lime Starvation Treatment in Tuberculosis. He also first pointed out and emphasized the therapeutic importance of regarding the combination of lime phosphate and casein, as brought down by the rennet enzyme, as a chemical union.”
This overworked lime-starvation theory certainly lacks any tangible confirmation (see in this connection a recent paper by Halverson, Mohler and Bergeim, in The Journal, May 5, 1917), and to urge it to promote the sale of a fat preparation is preposterous. On the uninitiated the exaggerated pseudo-scientific language of the pamphlet and circular advertisement will probably make some impression. Unfortunately such things count not only with the layman who, having no technical knowledge of physiology, cannot be expected to weigh the evidence but also with those medical men who, while scientifically educated, are influenced by unscientific claims when plausibly presented. The pamphlet is a striking example of a style which is dangerous because it smacks of science.
The Russell Company sells also a mixture called “Prepared Green Bone,” said to be made by partially digesting ground chicken bones with hydrochloric acid and pepsin and adding glycerin at the end of the digestion. The product is a sticky, unappetizing looking mass, put up in little earthenware boxes and advertised as a lime food, apparently to go along with the fat emulsion. The greater value of a few glasses of milk daily is evidently overlooked.
“The Russell Emulsion” and “The Prepared Green Bone” were declared inadmissible to New and Nonofficial Remedies.
[Editorial Comment.—There are always those who are ready to exploit the unfortunate tuberculous. It is, unfortunately, a fact that many physicians accept as true, statements clothed with obscure and voluminous quasi-scientific verbiage. Such men would laugh at the bald claim that the moon is made of green cheese; when, however, one plausibly and with due solemnity, affirms that the nocturnal luminous earthly satellite is composed of an infinite aggregation of molecules of bewildering and awe-compelling complexity, built up from the recently discovered polypeptids, the whole being of a verdant tint, the person addressed looks impressed and opines that it sounds reasonable! The advertising for The Russell Emulsion and The Russell Prepared Green Bone is dangerous because it appeals to the thoughtless—layman and physician, alike.]—(From The Journal A. M. A., June 23, 1917.)
BROM-I-PHOS
Report of the Council on Pharmacy and Chemistry
Brom-I-Phos (National Drug Company, Philadelphia) was submitted to the Council with a label bearing the following statement:
“ ‘ALCOHOL 25 PER CENT.’
COMPOSITION—Per Fluidounce
Iodin1 gr.
Bromin1 gr.
Phosphorus8-100 gr.
Aromatic Baseq. s.”
A request for further information in regard to the composition of Brom-I-Phos was sent to the National Drug Company. It was suggested that since the preparation cannot contain the stated amounts of free bromin, free iodin and free phosphorus, the form of combination in which these elements are present should be set forth. In reply, the firm said, first, that “Brom-I-Phos consists of Bromin, Iodin, Phosphorus, Glycerin, Wine, Water and Volatile Oils. The Iodin is rubbed up with a small percentage of Potassium Iodid and 95 per cent. Alcohol, which solution is mixed with a solution of Bromine and Spirits of Phosphorus which are combined with the base and aromatics.” The manufacturer also admitted that phosphorus reacts with bromin and iodin and that other reactions might occur, but maintained that it was “justified in assuming the greater part, if not all of these elements, are actually existent in the nascent state,” and asserted that its “printed formula complies with our working formula in point of quantities involved as well as existence of elements in an uncombined state.”
The A. M. A. Chemical Laboratory reported, on the contrary, that no free phosphorus, free bromin or free iodin could be found in Brom-I-Phos, and that no bromate or iodate could be found; bromid and iodid were present. The addition of silver nitrate to an acidulated portion, diluted with water, gave an amount of silver halid roughly agreeing with that which would be obtained had the claimed amount of bromin and iodin (together with some potassium iodid) been used in the preparation of Brom-I-Phos and in the process of manufacture become converted to bromid and iodid.
The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies, for conflict with Rules 1, 4, 6, 8 and 10.
The statement of composition is unsatisfactory and misleading in that it suggests that the preparation contains bromin, iodin and phosphorus in the free (elementary) state. The presence of the potent elementary phosphorus is especially suggested by the small amounts of “phosphorus” declared.
The following statement on the label of the trade package constitutes an indirect advertisement to the public:
“INDICATIONS: Scrofula, Coryza, Hay Fever Necrosis, Bronchial and Throat Affections, Catarrhal Pneumonia, Glandular enlargements of the Spleen, Thyroid, and Lymphatics, Rickets and Syphilis.”
The following claims are therapeutic exaggerations:
“The Ideal Alterative”
“... indicated in all cases where an alterative is desired ...”
“The association of Bromin with Iodin in Brom-I-Phos materially enhances the product in the treatment of chronic affections of the skin, depraved conditions of the mucous membranes, tertiary syphilis, glandular enlargements, etc.”
In that it suggests that the phosphorus in Brom-I-Phos is more readily assimilated than ordinary phosphate, the following is misleading:
“The Phosphorus contained in Brom-I-Phos is readily assimilated and at once acts as a nutrient to the nervous and osseous structures of the body, stimulates metabolism and increases mental activity.”
The recommendation: “Your specification of Brom-I-Phos in the treatment of Syphilitic cases will immediately prove beneficial to the patient” is not supported by evidence. The name does not indicate that Brom-I-Phos is an alcoholic preparation with iodid as its essential constituent, but suggests that phosphorus is an important constituent, whereas the amount of phosphate or phosphite, produced by the action of iodin on elementary phosphorus (if the amount of phosphorus used in making the preparation is correctly stated) is insignificant.
The combination of bromin, iodin and phosphorus, or bromid, iodid and phosphate, is irrational because these elements are not of mutual assistance to each other in the conditions for which Brom-I-Phos is advertised.
The Council’s report was submitted to the manufacturer of Brom-I-Phos for comment; the reply contained nothing to permit a revision of the previous conclusions.
The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies.—(From The Journal A. M. A., June 30, 1917.)
CREOSOTE-DELSON AND CREOFOS
Report of the Council on Pharmacy and Chemistry
Creosote-Delson and Creofos, or Creosote with Hypophosphites, were submitted by the Delson Chemical Co., Inc., New York City. Creosote-Delson is said to be “beechwood creosote from which the irritating and caustic properties are removed by fractional distillation.” It is claimed that Creofos contains “2 grains of Creosote-Delson and 33⁄5 grains of the combined Hypophosphites in each fluidrachm of the mixture or emulsion, the lime salt predominating.” It is also claimed that “the primary object of the hypophosphites in this preparation is that of maintaining the refined creosote in a pure, unoxidized state, and that no particular claim for therapeutic action on their part is advanced.” It is explained further, however, “the addition of the lime was prompted by the belief ... that the fundamental cause of pulmonary tuberculosis is lime starvation....”
The assertions are made that Creosote-Delson is superior to the official creosote because it can be taken “abundantly and persistently without harm to or interference with stomach and kidneys” and can be “taken uninterruptedly and indefinitely,” while the dosage is “unlimited by any former knowledge of Creosote Therapy.” Creosote-Delson is not on the market except in the combination Creofos, although it is supplied on request.
Creofos is advised in the treatment of tuberculosis, whooping cough, measles, “Grippe and Colds,” bronchitis, asthma, “Intestinal Affections (Colitis, Summer Diarrhoea, etc.),” while its use is suggested for the “prevention of the spread of contagious diseases,” and for “preventing contagion in minor contagious diseases at any rate, in schools and families.”
The following advertisement has recently appeared in the New York Medical Journal and in the Therapeutic Gazette:
CREOFOS MEDICATION
is the successful development of the most advanced practice in the treatment of infectious diseases. It destroys completely the causative organisms by a bactericide many times more powerful than phenol, yet absolutely harmless to animal life.
Unlike serums, its activity is not confined to any specific disease, and its use insures against sequelae (as pneumonia following grippe).
Especially valuable in the treatment of infants and patients of delicate constitution and in cases where time is of importance.
The Delson Chemical Co. was requested to supply information regarding the identity of Creosote-Delson and to support the claim that although it is “the whole drug” its dosage is “unlimited by any former knowledge of Creosote Therapy.” The reply was virtually an admission that the toxic, caustic, phenolic components of creosote were present in Creosote-Delson just as in the official creosote.
The referee of the Committee on Therapeutics in submitting his report to the Council pointed out that it is difficult to discuss the pharmacologic merits of a semisecret preparation, like Creosote-Delson, claimed to be more acceptable to the human organism than the official product it is intended to supplant, when the action of the parent drug is still questioned or disputed by eminent clinicians.
Absorption experiments have been carried out with creosote and creosote compounds, such as creosote with hypophosphites or calcium or creosote carbonate, chiefly by a study of the elimination products in the urine. But any evidence so far offered that these combinations increase absorption and lessen the irritating, caustic or toxic properties has been wholly inconclusive. The evidence offered by the Delson Chemical Co. presented no control experiments with the official creosote and did not prove that either Creosote-Delson or Creofos was less toxic than a corresponding amount of ordinary beechwood creosote.
The referee concluded that no proof had been offered that these preparations are materially superior to ordinary creosote preparations from the pharmacologic or therapeutic standpoint, and that the claims made for Creosote-Delson and Creofos are unwarranted in the light of our knowledge of the properties of creosote. The advertisement quoted above is an example of unproved and unwarranted claims.
On the recommendation of the referee, the Council declared Creosote-Delson and Creofos inadmissible to New and Nonofficial Remedies, for conflict with the rules as follows:
Creosote-Delson: The information so far available is not sufficient to define the nature, or composition, of Creosote-Delson, or to indicate in how far this product differs, if at all, from the official creosote (conflict with Rule 1). No methods are furnished for determining the identity or composition of Creosote-Delson (conflict with Rule 2). The available information does not show that Creosote-Delson has advantages over creosote (conflict with Rule 6).
Creofos: The composition of Creosote-Delson not having been furnished, the statement concerning the composition of Creofos is also unsatisfactory (conflict with Rule 1). The therapeutic claims are unsubstantiated and grossly exaggerated (conflict with Rule 6). The name is not descriptive of its composition as is required for pharmaceutical mixtures (conflict with Rule 8). There is no evidence that hypophosphites prevent decomposition of creosote (if this occurs). Hence the inclusion of hypophosphites must be considered irrational (conflict with Rule 10).
The Council’s report was sent to the Delson Chemical Co. for consideration. The firm’s reply contained nothing to warrant a revision of the report, and the Council voted that Creosote-Delson and Creofos were inadmissible to New and Nonofficial Remedies and authorized the publication of this report.—(From The Journal A. M. A., July 7, 1917.)
TRINER’S AMERICAN ELIXIR OF BITTER WINE
Report of the Council on Pharmacy and Chemistry
Triner’s American Elixir of Bitter Wine is a wine to which bitter drugs and laxatives have been added. Though evidently intended for public consumption, it is also advertised to physicians, and consequently the Council publishes this report.
Some recent advertisements read:
“It Acts Well and Is Very Palatable. These are the reasons why so many physicians recommend TRINER’S AMERICAN ELIXIR OF BITTER WINE. Free from any chemicals. Prepared from bitter herbs roots and barks of eminent medicinal value and pure natural red wine. A safe relief in auto-intoxication, constipation, weakness, etc. Price $1.00. At drug Stores. Samples gratis upon request only to physicians.”
“A Laxative Tonic. In cases of constipation and its sequelæ, autointoxication, weakness and nervousness you should try Triner’s American Elixir of Bitter Wine. This preparation consists of Cascara Sagrada, Dandelion, Gentian Root, with Licorice in Pure Red Wine as a base, with Aromatics.”
Triner’s American Elixir of Bitter Wine is put up in bottles said to hold 1 pint, 51⁄3 fluidounces. The label declares the presence of from 16 to 18 per cent. alcohol by volume, and states that “no special tax is required by the laws of the U. S. for the sale of this medicinal preparation.” The circular contains the following recommendations for its use:
“... It should be used in all cases calling for a safe evacuation of the bowels, without weakening the body or causing any pain or other discomfort; in loss of appetite, nervousness and weakness.”
“Triner’s American Elixir of Bitter Wine consists of two principal ingredients, viz., Red Wine and Medicinal Herbs.”
“Red Wine strengthens the intestines and regulates their work. It also increases the appetite, stimulates and strengthens the body.”
“Use Triner’s American Elixir of Bitter Wine always when a thorough cleaning out of the intestines is needed. Arrange the dose to suit your condition and habits.”
“In Chronic Constipation the dose of Triner’s American Elixir of Bitter Wine should be increased or taken oftener.”
“Many Female Troubles are caused or aggravated by constipation and ladies should always pay good attention to this fact.”
In addition to Triner’s Elixir of Bitter Wine, the circular—in English, Polish, Russian, Spanish and other languages—advises the use of Triner’s Angelica Bitter Tonic, Triner’s Red Pills, Triner’s Liniment and Triner’s Cough Sedative.
The composition of this “wine”—some bitter drugs, a laxative and a tannin-containing, constipating red wine—and advertising propaganda all tend to the continued use of this alcoholic stimulant and thus to the unconscious formation of a desire for alcoholic stimulation. As the medical journal advertisements may lead physicians to prescribe this secret and irrational preparation and thus unconsciously lead to alcoholism, the Council authorized publication of this report.—(From The Journal A. M. A., July 14, 1917.)
TRIMETHOL
Report of the Council on Pharmacy and Chemistry
Trimethol is the trade name for a substance said to be trimethyl-methoxy-phenol of the formula C6H(CH3)3(OCH3).OH—1:2:4:5:6, originated by J. T. Ainslie Walker. It is sold as a nontoxic germicide, having a Rideal-Walker phenol-coefficient of 40, even in the intestinal canal. It is described as insoluble in water and not to be decomposed in the alimentary tract, and to be excreted unchanged in the feces.
Trimethol itself is not obtainable. Pharmaceutical preparations—Trimethol Syrup, Trimethol Capsules and Trimethol Tablets, said to contain Trimethol—are prepared by The Walker-Leeming Laboratories and sold by Thos. Leeming and Co., New York.
Trimethol preparations are advertised for use in all conditions dependent on intestinal putrefaction. The advertising claims made are very extensive and some of them give to “Trimethol” the scope of a panacea. For example:
“Physicians are constantly reporting cases where Trimethol has been especially efficient, and describing conditions (until recently not associated with intestinal infection) which have been distinctly benefited by its use. This would seem to bear out the contentions of Charcot and Metchnikoff that 90% of all human ailments have their origin in intestinal infection.
“The careful practitioner, when in doubt, will bear this in mind, now that we have a really efficient and non-toxic intestinal germicide—not a mere antiseptic.”
The Walker-Leeming Laboratories have not formally requested the Council to consider the Trimethol preparations, though in a personal letter to a member of the Council J. T. Ainslie Walker invited an investigation of his compound.
For the investigation of Trimethol and its preparation the Council secured the aid of a bacteriologist who has given much attention to the study of the intestinal flora. The Walker-Leeming Laboratories and J. T. Ainslie Walker were both asked to submit details of experimental studies and also to furnish a supply of the pure “Trimethol.” But the only data sent that had any definiteness set forth the bacterial counts made of plate cultures of stools of one patient before and after the administration of Trimethol Capsules.
REFUSE TO FURNISH TRIMETHOL
The request for the pure substance was refused, on the grounds that the substance was not used in the undiluted form. The failure to furnish the chemical substance claimed as the essential constituent of the Trimethol preparations is to be deprecated if indeed it has not greater significance. At least it made it impossible for the Council’s expert to express his results in terms of absolute Trimethol of established composition. The data obtained apply only to the market preparations claimed to contain Trimethol. So far as the investigation and report go, “Trimethol” is a hypothetical substance.
Clinical or animal tests of the asserted intestinal antiseptics have hitherto given equivocal results because it is impossible, on the one hand, to predict the course of any intestinal infection, or, on the other hand, to determine what effect, if any, was produced by administration of the medicament. It therefore seemed unwise to undertake this line of investigation until the more direct laboratory bacteriologic methods had been exhausted. Consequently the investigator checked, in the first place, the phenol coefficient of one of the Trimethol preparations and then also determined its “penetrability” coefficient. Although by both methods Trimethol was found to be a germicide, the results did not indicate any remarkable potency or other properties suggesting that the drug possessed special therapeutic value. From the results obtained it appeared inadvisable to proceed further with the work until more definite evidence of the nature and of the value of the substance should be at hand. The report of the bacteriologic investigation follows:
THE BACTERIOLOGIST’S REPORT
“I have made no attempt to study the effects of internal administration of Trimethol on the intestinal flora. The methods available at the present time of enumerating the numbers of viable bacteria in the feces are probably not accurate within 100 per cent. and the precision of such determinations is equally variable. The physiologic factors involved are so complex that they would appear to make a really valuable assay a question of many months’ careful study. If it were possible to administer known amounts of Trimethol, as such, the problem might be worth while; inasmuch as the available reactive substance is not at present quantitatively assayable, this phase of the investigation barely seems practicable.
“ ‘Trimethol Syrup,’ as such, appears to be about 10 per cent. as efficient in its germicidal value as carbolic acid. If the assay, 3⁄4 m. Trimethol per drm. (as the label indicates), is correct, the substance would appear to possess germicidal merit provided enough could be administered, if it is not influenced by passage through the stomach.
“A package containing four four-ounce bottles labeled ‘Trimethol, A Non-Toxic Germicide SYRUP Representing 3⁄4 m. Trimethol per drm., Alcohol 11⁄2 per cent.’ was received at the laboratory Dec. 15, 1916. Later a smaller package containing, according to the label, 100 Trimethol tablets, each 5 gr., representing 11⁄4 m. Trimethol, was received. The tablets were apparently chocolate coated.
“Two separate series of tests were made upon the syrup. (a) Phenol coefficient, using the method outlined in Bulletin No. 82, Hygienic Laboratory, Method of Standardizing Disinfectants With and Without Organic Matter. (b) A Penetrability coefficient by the method of Kendall and Edwards, Journal of Infectious Diseases, 8, 250.
“The former method compares the viability of naked germs in a 1 per cent. carbolic acid solution as a standard, with various dilutions of the germicide to be tested. The latter measures the relative diffusibility and germicidal power of carbolic acid and various dilutions of the germicide to be tested upon Bacillus coli suspended in 1.2 per cent. agar which is molded in cylinders of one centimeter diameter after infection with the organism.
“The first method—phenol coefficient—possesses advantages and disadvantages which are well known and need no mention here. It is worthy of notice, however, that as the death rate of the bacteria increases during the progress of the test, it becomes increasingly difficult to maintain a uniform suspension of living organisms so that each loopful removed shall exactly represent the developmental potentiality of the residual organisms.
“The second method theoretically covers the possibility because all the organisms are immobilized and are exposed to the germicide in direct proportion to its diffusibility until the center of the agar mass is reached, where the residual viable bacteria are presumably located. Inasmuch as the penetrability of an intestinal mass is involved in a discussion of intestinal germicides, the propriety of utilizing this ‘penetrability coefficient’ in this connection is obvious, in spite of its patent shortcomings.
“It is unnecessary to discuss the technique—the standard broth mentioned in the Hygienic Bulletin, a temperature of 70 F., a standard 4 mm. loop and careful attention to dilutions (using distilled water) were all observed. The various dilutions of Trimethol Syrup were made with accurate volumetric pipettes, measuring flasks and distilled water was used as a diluent.
“The results of several determinations, using Trimethol Syrup from three separate bottles, were in sufficient accord to warrant the statement that a dilution of 1⁄10 of Trimethol Syrup was equivalent to a 1⁄100 dilution of carbolic acid, using Bacillus typhosus as the test organism. Both solutions—the Trimethol and phenol—killed the organism in the interval between 71⁄2 minutes and 10 minutes’ exposure. That is to say, our observations indicate that under standard conditions as defined above, a 10 per cent. solution of Trimethol Syrup is equivalent in germicidal powers, as defined by the phenol coefficient to a 1 per cent. solution of phenol. Naturally, no predictions can be drawn from these observations indicative of the value as an intestinal germicide of Trimethol itself.
“The Penetrability coefficient resulted as follows: A 5 per cent. solution of phenol killed Bacillus coli, suspended uniformly throughout a cylinder of 1.2 per cent. agar in the interval between 60 and 90 minutes. A 1 per cent. solution of phenol killed the same organisms under the same conditions in the interval between two and one half and three hours. An undiluted solution of Trimethol Syrup killed the organisms in the interval between two and one half and three hours. A 10 per cent. solution (nine volumes of distilled water to one volume of Trimethol Syrup) failed to kill the organisms in four hours. It would appear that undiluted Trimethol Syrup has the same combined penetrability and germicidal value as a 1 per cent. phenol solution.
“The Phenol coefficient: A 10 per cent. solution of Trimethol Syrup in distilled water (nine volumes of distilled water to one volume of Trimethol Syrup) possesses the same germicidal power as a 1 per cent. solution of carbolic acid. This coefficient takes no cognizance of the actual amount of Trimethol as such—it merely indicates the relative germicidal power of the Trimethol Syrup as sold.”
The preceding report shows that Trimethol Syrup has a phenol coefficient of 1⁄10, and, assuming Trimethol Syrup contains the amount of Trimethol declared, the substance Trimethol would have a phenol coefficient of 81⁄3 instead of 40, as is claimed. According to Kendall and Edwards’ method, the penetrability-germicidal value of the syrup is equal to a 1 per cent. solution of phenol.
WALKER’S REPLY TO CRITICISM
The report of the bacteriologist was submitted to The Walker-Leeming Laboratories for comment. The following reply was received from J. T. Ainslie Walker:
(May 22, 1917) “In reply to your letter of the 15th inst., which has just been placed before me on my return to town, I have to inform you that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid.
“As you will see from the enclosed extracts from clinical reports, the therapeutic value of Trimethol has been well established.
“As regards penetrability, no claim has ever been made for Trimethol in this connection; and, as I pointed out in my original paper (American Medicine, September, 1914), when referring to the independent tests made by Dr. Frederick Sondern, ‘No attempt was made to determine the bacterial content of the solid particles, as in the opinion of the writer sterilization of the interior of these particles is not only absolutely impossible, but wholly unnecessary. The fact of the fluid contents of the canal being sterile may be taken to indicate that the exterior of all solid particles is in a like condition, and therefore harmless. It is the organisms in the fluid portions only that produce the deadly effects through the chemical substances they secrete; those in the interior of the solid portions (i. e., as evacuated) may be disregarded, as they are not available for good or evil.’
“I must confess to no little surprise on learning that your investigator is still using the Hygienic Laboratory method of determining phenol coefficients. I would respectfully suggest that you call his attention to the critical comparison of the Hygienic Laboratory and R.-W. Tests, which he will find in the enclosed reprint from the New York Medical Journal of March 11, 1916: ‘Instead of being an improvement upon the standard R.-W. Test, the so-called Hygienic Laboratory Method is so defective as to be wholly unreliable, and incapable of furnishing results of any scientific or practical value whatever.’ ”
As to the statement that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid, attention is called to a leaflet, which accompanies each bottle of Trimethol Syrup, that reads:
“Trimethol is insoluble in water, but when properly emulsified has a Rideal-Walker co-efficient of 40; that is to say, it is 40 times more efficient as a germicide than phenol (pure carbolic acid).”
The Trimethol Syrup which was used in the investigation, when mixed with water produced an almost perfectly transparent solution, which justifies the assumption that the proper physical conditions were observed and that this objection is not well founded.
As regards the relation of pancreatic fluid to bactericidal availability of Trimethol, there is little to say, other than that the published statements in the advertising accompanying the packages make no mention of this point. It would be interesting to know what, if any, relation the pancreatic fluid has to this substance, in view of the statement that it “has a Rideal-Walker coefficient of 40.”
The Trimethol “literature” does not throw light on the question, What is the germicidal value of Trimethol Syrup as compared with phenol? The only available method of determining the germicidal value of a liquid disinfectant is to make a direct comparison of the substance in question with phenol under similar conditions. Given parallel conditions, not obviously prejudicial to the substance tested in contrast to the standard solution, the results are comparable, and furnish a basis for estimating the relative germicidal power of the two substances. In the investigation, Trimethol Syrup and phenol were thus compared.
As regards the contention that the bacteria within fecal masses are harmless, this may be granted. But it must also be admitted that these intestinal masses are constantly being reformed so that buried micro-organisms do not remain in the interior. For this reason, the determination of the penetrability coefficient of a germicide is pertinent.
Regarding the respective merits of the old Rideal-Walker and the newer U. S. Hygienic Laboratory method of determining the phenol coefficient, the Rideal-Walker method was found to possess certain drawbacks, and in an attempt to overcome these the “Lancet Method” was evolved; this method in turn was improved in the U. S. Hygienic Laboratory and led to the United States Public Health Service Hygienic Laboratory method for the determination of the phenol coefficient of disinfectants (published in Hygienic Laboratory Bulletin 82). In 1913 this method was formally adopted by the Council for the valuation of disinfectants or germicides of the phenol type, and the method is now in general use for this purpose in the United States.119 In this connection Hiss and Zinsser may be quoted (Ed. 2, page 80): “The most precise method of standardizing disinfectants is that now in use in the United States Public Health Service.” Stitt, director of the United States Naval Medical Schools, in his Practical Bacteriology, Blood Work and Parasitology (Ed. 4, page 473) says: “In the United States disinfectants are rated according to the Hygienic Laboratory Phenol Coefficient.”
The Council adopted the recommendation of the Committee on Pharmacology to the effect that the claims made for Trimethol are unsupported by acceptable evidence. Accordingly, Trimethol and the pharmaceutical preparations said to contain it—Trimethol Syrup, Trimethol Capsules, and Trimethol Tablets—were held ineligible for New and Nonofficial Remedies.—(From The Journal A. M. A., Aug. 11, 1917.)
FERRIVINE, INTRAMINE AND COLLOSOL IODINE
Report of the Council on Pharmacy and Chemistry
E. Fougera & Co., Inc., New York, acting as agent for The British Drug Houses, Ltd., London, advertise “Ferrivine,” “Intramine” and “Collosol Iodine” to the medical profession. A circular entitled “Ferrivine, The New Anti-Syphilitic Remedy” begins:
“FERRIVINE is the name given to ferric tri-para-amino-benzene sulphonate. This iron compound was first prepared by Mr. J. E. R. McDonagh, F. R. C. S., by whom it has been both biologically and clinically tested. It is slightly soluble in water, the solution having an acid reaction.
“INDICATIONS
“According to Mr. J. E. R. McDonagh’s researches, the phases of the Leucocytozoon syphilids are killed by the lipoid-globulin molecules of the serum, which possess a stereochemical molecular configuration homologous to those of the lipoid-globulin molecules of the parasite. The process is one of absorption, a chemico-physical reaction which is in part dependent upon the supply of active oxygen. Active oxygen is formed directly by oxidation processes and the peroxide necessary for its formation directly by reducing processes. Oxidation is increased by metals and reduction by non-metals. The non-metal which acts in the body as the normal reducing agent is sulphur, hence the discovery of Intramine (see separate pamphlet). The metal which acts in the body as the normal oxidising agent, is iron, hence the discovery of Ferrivine.”
A circular, “Intramine, a New Non-Toxic Compound for the Treatment of Protozoal and Chronic Bacterial Diseases,” expounds Mr. McDonagh’s ideas of the treatment of syphilis with Ferrivine and Intramine by means of the oxidising action of Ferrivine and the reducing action of Intramine and asserts:
“As the ultimate administration of oxidising and reducing agents will benefit almost any infection, it may be said that Intramine is indicated in all protozoal diseases, and in all chronic bacterial diseases, especially in tuberculosis, presumably in leprosy and possibly in malignant disease [cancer?]. To the administration of Intramine there are no contraindications.”
We are also told that:
“Intramine is useful injected into the urethra.... In cases of chronic urethritis and perifolliculitis ... invaluable as a local application to chronic ulcers ...”
The Intramine circular includes a “Scheme of Treatment for Syphilis” which advises, in addition to Intramine, Ferrivine or salvarsan, mercury and iodids, the use of another proprietary called “Collosol Iodine.” An inquiry addressed to Fougera & Co. in regard to the character and composition of this preparation, brought the reply that the firm had no knowledge of its identity.
This “scheme of treatment” is objectionable in that it advises the “stock” treatment of a disease which demands individualization and further in that whatever beneficial effects may result from the use of mercury and iodid is likely to be ascribed to the preparations “Intramine,” “Ferrivine” and “Collosol Iodine.”
The advertising for Ferrivine and Intramine sent out by Fougera & Co. contains no experimental or clinical data on which an estimate of their value may be based. Apparently in England, where these products were originated, little has been published regarding them.
There is, however, one report which may be accepted as a carefully controlled clinical trial. In the Lancet (June 17, 1916, p. 1214) L. W. Harrison, D.S.O., M.B., Ch.B.Glasg., and C. H. Mills, M.R.C.S., L.R.C.P.Lond., report on “The Effect of Ferrivine and Intramine on Syphilis.” After briefly reviewing the theories which form the basis of McDonagh’s proposed treatment of syphilis with his discoveries “Ferrivine” and “Intramine” the authors point out:
“... that Mr. McDonagh’s biological discoveries ... have not been publicly confirmed by any biologist of standing ...”
While:
“... eminent chemists have confessed themselves unable to understand his chemistry.”
The authors explain:
“Recognizing that this might prejudice our practical tests of Intramine and Ferrivine, we have taken particular care to guard against their influence, cross-checking our observations and submitting them to others for confirmation or otherwise.”
Harrison and Mills chose for a test three ordinary cases of secondary syphilis, cases with well marked lesions, the clinical progress of which could easily be watched and from which it was easy to obtain specimens for microscopic examination. After a detailed account of the three cases—which records grave conditions resulting from the treatment and which shows the inefficiency of the drugs—they write:
“From the above account it will be seen that the local and general reactions which follow the injection of these preparations are by no means pleasant. In the case of Intramine the pain is undiluted torture and lasts so for two or three days. One of us had previously treated four cases with Intramine and the same local reaction occurred in these. In two of them abscesses have burst outwardly, one of which is still discharging necrotic débris, ten weeks after the injection, and will take many more weeks to close. In those cases where no abscess has yet burst it is easy to feel by the gap in the muscles that considerable necrosis has occurred. None of these effects can be ascribed to sepsis, as most rigid aseptic precautions were taken. Further, particular care was taken to make the injections strictly intramuscular. The constitutional symptoms which follow immediately upon the injection of Ferrivine are distinctly alarming, and such as would cause one to hesitate before injecting this remedy into any but robust patients.”
Harrison and Mills estimate the therapeutic effects of these drugs thus:
“1. That Ferrivine entirely failed to cause S. pallida to disappear from the lesions of three well-marked cases of secondary syphilis.
“2. After the failure of Ferrivine to cause the disappearance of Spirochaeta pallida from a mucous patch a single dose of 0.3 gm. salvarsan effected this in 18 hours, and the patch, which had hitherto been uninfluenced, had healed within 48 hours.
“3. Clinically we were unable to detect any influence of either or both these compounds on syphilitic lesions, although each of them was of the variety which heals in a week or ten days under salvarsan treatment.
“4. Further syphilitic lesions appeared immediately after the treatment in one of the two cases treated with both Ferrivine and Intramine. A mucous patch appeared on one tonsil as well as further syphilitic papules from which spirochetes were obtained. The other case developed nephritis, with albumin and epithelial casts; which was not present prior to the injections.”
While from these cases the obvious conclusion was drawn that Intramine and Ferrivine “have no specific effect on early syphilis,” these authors subsequently treated a case of tertiary syphilis with the drugs. An Intramine injection caused pain for several days but did not stop the progress of the disease. Ferrivine was then administered “not without a feeling of grave responsibility” in view of their previous experiences. They state that “the reaction which resulted in this instance was the most severe” they ever experienced after an intravenous injection of any of the antisyphilitic remedies with which they had previously worked. It is stated that “for a period of some minutes there was grave doubt as to the patient’s survival.” After resuscitation the patient passed a disturbed night, and rigors which ensued lasted until the following afternoon. The author’s report that in this case also no clinical improvement occurred and that the Intramine-Ferrivine treatment was replaced by a course consisting of salvarsan, potassium iodid and mercurial inunction.
Ferrivine, Intramine and Collosol Iodine were declared inadmissible to New and Nonofficial Remedies.—(From The Journal A. M. A., Sept. 8, 1917.)
ESKAY’S NEURO PHOSPHATES
Report of the Council on Pharmacy and Chemistry
For the information of the profession the Council has prepared and authorized for publication the following report on Eskay’s Neuro Phosphates.
W. A. Puckner, Secretary.
Eskay’s Neuro Phosphates (Smith, Kline & French Co., Philadelphia) is offered to physicians under the claims that it contains alcohol, 17 per cent., and sodium glycerophosphate, 2 grains, calcium glycerophosphate, 2 grains, and strychnin glycerophosphate, 1⁄64 grain, in each dessertspoonful. It is called a “Nerve Tissue Reconstructive,” and its advertising claims are based on the discredited theories that certain disorders are due to a deficiency of phosphorus in the nerve structure of the body, and that glycerophosphates are assimilated more readily than ordinary phosphates. This assumption was based on the knowledge that the lecithins, which form a part of the nerve structure, contained the glycerophosphate radical in the molecule. In line with this, Smith, Kline & French Co. aver:
“Eskay’s Neuro Phosphates is of marked value in many acute and chronic conditions, in nervous exhaustion following mental and physical strain, neurasthenia, paralysis, anemia, tuberculosis, marasmus, debility and wasting diseases generally, and the nerve-weakness of the aged. It is particularly useful in convalescence from acute diseases and in the nervous condition following la grippe.”
In its report on “The Therapeutic Value of the Glycerophosphates” (The Journal, Sept. 30, 1916, p. 1033) the Council pointed out that the therapeutic use of the glycerophosphates was based on the assumption that the inorganic phosphates cannot supply the body’s needs of phosphorus or that the use of organic compounds “spared” the system the necessity of making such synthesis. The report presented evidence to show that the glycerophosphates are not absorbed as such, but that they are split into inorganic phosphates before absorption. The Council showed that there was convincing evidence that the animal organism synthesizes its complex organic phosphorus constituents from inorganic phosphates, and that organic phosphorus is of no more value as a food than inorganic. Despite this the Neuro Phosphates advertising makes use of the fallacious assumption regarding the action of the glycerophosphates.
Pleading for the particular mixture represented by the proprietary, it is asserted that:
“Sodium glycerophosphate is of special value in neurasthenia, Addison’s disease, phosphaturia and phthisis.”
and that calcium glycerophosphate “is employed in bone fracture, rachitis, tuberculosis and various wasting diseases.”
The phosphorus content of 1⁄64 grain of strychnin glycerophosphate is ridiculously small. Yet it is asserted that this strychnin salt is of superior value because it combines the effects of strychnin with a “food-like form of phosphorus.” Eskay’s Neuro Phosphates has an acid reaction which is capitalized, thus:
“Experiments have shown that the acid glycerophosphates are more rapidly absorbed and are more efficient than the neutral salts.”
And as a further illustration of extravagant claims:
“As a glycerophosphoric acid in the form of lecithin is normally present in spermatozoids, it is but natural that the glycerophosphates should exhibit aphrodisiac effects (as has been observed), but this result does not seem to obtain in all cases.”
Is this a clumsy attempt to exploit this “nerve phosphate” as a “lost manhood” cure?
The Council held Eskay’s Neuro Phosphates ineligible for New and Nonofficial Remedies because unwarranted therapeutic claims are made for it and because the administration of strychnin, calcium, phosphate and alcohol is not conducive to rational therapeutics, particularly when such a mixture is marketed under a name which indicates but one of its constituents.—(From The Journal A. M. A., Sept. 29, 1917.)
K-Y LUBRICATING JELLY
Report of the Council on Pharmacy and Chemistry
Because of inquiries received, the Council has authorized publication of the following report declaring K-Y Lubricating Jelly inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
K-Y Lubricating Jelly (Van Horn and Sawtell, New York), originally advertised as a lubricant for instruments and the hands, is now also recommended as a therapeutic agent. If the claims for “K-Y” were limited strictly to such effects as result from the purely mechanical properties of a lubricant, it might be held that it would not come under the purview of the Council. The preparation, however, while introduced as a lubricant, is now offered for a broader field of use, and the manufacturers make claims which are not supported by any evidence available to the Council. Evidence the following, taken from a circular that accompanies the package:
“K-Y allays smarting and burning at once through its pronounced soothing and cooling effects, and thus makes an admirable dressing for burns.”
“Many physicians make a practice of anointing the bodies of their measle and scarlet fever patients with ‘K-Y,’ in this way affording gratifying relief from itching and irritation, and effectively preventing dissemination of infectious material.”
And this from another circular:
“I had one of the most troublesome cases of pruritus vulvæ that I had ever seen. I guess I must have tried everything and the case had been referred to me by another man, who had previously tried everything, including cauterization. Well, one day I was examining her, and of course K-Y on the speculum—the irritation seemed to quiet down, and the following day she said she felt no effects from it at all. Then later on, it returned, and I couldn’t imagine what had done so much good, unless it could have been the lubricant, so I told her to buy a tube, which she did. Every once in a while she has a return of it slightly, but she just applies K-Y and clears it all up.”
The manufacturers state that they do not know why K-Y is so soothing, but suggest:
“Possibly the cooling action of the combination, and the effect of the 4% boric acid contained, are factors that enter. Be all that as it may, the fact certainly remains that oftentimes, after other local measures fail, ‘K-Y’ lubricating Jelly gives relief.”
Elsewhere it is claimed to be germicidal, and to give relief in other conditions, thus:
“Diabetic and uremic irritations, not only of the genitalia, but of other parts, have been found fully as amenable as pruritus vulvae to the soothing influence of ‘K-Y’ Lubricating Jelly, especially if the previous application is removed with water every time a new one is put on.”
The foregoing citations are obviously intended largely for the public, and make it plain that “K-Y” Jelly is not in the class of nonmedical and harmless external applications; on the contrary, these claims tend to create the impression that the spread of measles and scarlet fever can be prevented in the stage of desquamation. To place such statements in the hands of the patient supported by the tacit endorsement of a prescription is to create a false and dangerous sense of security and to lead to a failure to observe other and more important means of preventing dissemination of these diseases.
The Council held K-Y Lubricating Jelly in conflict with Rules 1, 4, 6 and 10, and authorized publication of this report.—(From The Journal A. M. A., Sept. 29, 1917.)
ZIRATOL
Report of the Council on Pharmacy and Chemistry
Ziratol (Bristol-Myers Company, New York), in compliance with the federal “insecticide law,” is declared to contain 32 per cent. water and 30 per cent. glycerin as inert constituents. Regarding its active constituents the manufacturer makes the following and meaningless statement:
“Ziratol is prepared from Phenols of the Naphthalene series and consists of a solution of such Phenols in a mixture of soap, water and glycerin.”
In response to inquiry, the A. M. A. Chemical Laboratory examined Ziratol and reported that its essential constituent appears to be alpha-napthol,120 and that it has, essentially, the following composition by weight: Alpha-napthol 18 per cent., soap 20 per cent., glycerin and water sufficient to make 100 per cent.
A Ziratol advertising circular gives a tabulated report of germicidal tests, said to have been made according to the method of the Hygienic Laboratory of the U. S. Public Health Service. When this work was done is not stated. According to these tests Ziratol possesses a phenol-coefficient of 13.66. The claim that Ziratol is ten times more efficient than carbolic acid (phenol) is evidently based on this report.
These claims of high germicidal value are contradicted by an examination made for the Council. A specimen purchased in the open market was examined independently by two operators, to determine the Hygienic Laboratory phenol-coefficient. One observer found the phenol coefficient to be 2.54. The other reported it to be 3.09. Evidently the germicidal value of Ziratol is greatly exaggerated in the advertising claims and, in fact, does not exceed that of the official compound solution of cresol (Liquor Cresolis Compositus, U. S. P.) for which a phenol-coefficient of about three has been established. (See New and Nonofficial Remedies, 1917, p. 82.) The claim that Ziratol is “the Universal Antiseptic and Germicide” is manifestly an unwarranted exaggeration.
The referee in submitting this report to the Council recommended that Ziratol be held in conflict with Rule 1 (secrecy of composition) and Rule 6 (unwarranted and exaggerated claims). After the report had been submitted, it was found that a new advertising circular, accompanying a trade package, no longer contained the claim that “Ziratol is ten times more efficient than Carbolic Acid.” The older circular made the following statement:
“1. Strong Activity.—Compared with the bactericidal action of Carbolic Acid by the method of the Hygienic Laboratory of the Marine Hospital Service, Ziratol has the Carbolic Acid Coefficient of more than TEN, that is, Ziratol is TEN times more efficient than Carbolic Acid,—a strength unapproached by any other of its class. Ziratol in dilution of 1:1400 kills the Typhoid Bacillus in 21⁄2 minutes, thus proving that it is strongly active even in very weak solutions.”
The new advertising circular reads:
“1. Strong Activity—Extensive bacteriological investigations on many pathogenic organisms, conducted in the Lederle Laboratories of New York, prove conclusively the high bactericidal value of Ziratol in extremely dilute solutions. (A copy of the complete report will be mailed upon request.)”
In response to a request, the Bristol-Myers Company sent a copy of the bacteriologic investigations of Ziratol, said to have been made by the Lederle Laboratories. The organisms employed for these tests were Staphylococcus aureus, Staphylococcus albus, Streptococcus, Green pus bacillus, B. coli, and saliva. No tests are given with the typhoid bacillus. The conclusion is reached that “in all the tests the solutions of Ziratol have several times greater killing efficiency than those of phenol.” The “coefficients” or comparative values which can be calculated from the results after exposure of 15 minutes to the disinfectants range from 2.0 to 4.0. This is in substantial accord with the referee’s findings as regards the phenol-coefficient with B. typhosus as the test object. While the new advertising circular avoids the former claim that Ziratol is ten times more efficient than carbolic acid, in germicidal value, it still makes the unwarranted claims that Ziratol is the “universal disinfectant.”
The Council declared Ziratol inadmissible to New and Nonofficial Remedies (1) because its composition is secret (Rule 1); (2) because the phenol coefficient, determined according to the method of the Hygienic Laboratory, U. S. P. H. S., is not stated on the label (Rule 2); (3) because the label and the circular accompanying the trade package advises its use by the public as a “vaginal douche” (Rule 3); and (4) because the claim that Ziratol is the “universal disinfectant” is exaggerated and unwarranted (Rule 6).
Before authorizing publication of the preceding report the Council submitted it to the Bristol-Myers Company in order to give that company the opportunity of revising its method of marketing Ziratol. In reply the company enlarged on its withdrawal (on “our own initiative”) of the claim that Ziratol had a phenol-coefficient of over ten when this claim was shown to be incorrect “by authoritative sources.” One wonders whether this is a euphemistic reference to the proceedings of the federal authorities under the Insecticide Act against the Bristol-Myers Company, just made public,121 because of the false claims made for the germicidal efficiency of Ziratol. This prosecution resulted in the seizure and condemnation of two lots of this proprietary which had passed in interstate commerce.
The Bristol-Myers Company in replying to the Council’s report made no offer to declare the exact composition of Ziratol, to state the actual phenol-coefficient, or to remove the other objections pointed out in the report of the Council. In other words, the Bristol-Myers Company has abandoned a definite but false claim of high germicidal power—a claim which subjected the firm to federal prosecution—and has substituted therefor indefinite statements which do not define the actual germicidal efficiency of Ziratol.—(From The Journal A. M. A., Oct. 6, 1917.)
GONOSAN
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report on Gonosan and authorized its publication.
W. A. Puckner, Secretary.
Gonosan (Riedel and Company, Inc., New York City) comes in the form of capsules, each said to contain 5 minims of a mixture composed of oil of sandalwood 80 per cent., and 20 per cent. of alpha- and beta-resin of kava, isolated by a patent process. The mixture, as the name implies, is intended for the treatment of gonorrhea.
This proprietary preparation was under consideration by the Council at various times from 1905 to 1910. During this time, the Council agreed to accept the preparation if the suggestive name was changed, the therapeutic exaggerations abandoned, and the drug kava admitted to New and Nonofficial Remedies. The name was not changed, the other questions were left open, and the preparation was not accepted.
Recent and more objectionable advertising of Gonosan makes it advisable for the Council to take action and to publish a report. The tone of this advertising is reflected by the following quotation from a recent advertising circular:
“The old-established balsamic treatment of gonorrhea, for some years neglected in favor of the local injection of organic silver and other germicidal salts, has, with the increasing knowledge and attention paid to the composition and purity of the balsams, regained to a large extent the confidence formerly reposed in them.
“It may now be said that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy.”
Any one conversant with current medical literature and practice would stamp these statements as misleading exaggerations. The balsams, oleoresins and volatile oils may have some value as minor adjuvants in the treatment of gonorrhea, but that is all. The position in this respect has not changed materially in recent years. These agents do not have a value equal to that of local treatment, as the quoted statement implies.
The claims made for Gonosan might with equal force be made for oil of santal alone. Kava kava, the other constituent, belongs to the pepper family; it had a temporary vogue some two or three decades ago, but has failed to maintain a place. It has never been recognized officially. There is no scientific evidence that it has any value either alone or as an adjuvant to sandal oil. The “clinical reports” quoted in the advertising circulars, rather curiously, nearly all date back ten years or more, viz., to a period when the attitude of the profession toward proprietary remedies was less critical than it is now. It would be interesting to know whether these authors still adhere to their opinion, or whether any of them have subsequently had experiences similar to that of a correspondent who wrote:
“Gonosan, at my hands, did not prove to be of more essential value in the treatment of gonorrhea than any other sandalwood oil preparation. The various claims made for Gonosan, that it possesses sedative and anesthetic properties, that by its continuous use the urethral discharge disappears more rapidly and that, if combined with appropriate diet and rest, it is liable to prevent complications, are, according to my experience, not corroborated by actual results.”
The only experimental work quoted in support of Gonosan, that of Pohl, is not convincing. The doses that Pohl found necessary to influence experimental purulent pleurisy makes it impossible to transfer his work to the clinic. (He found a dosage of oil of santal corresponding to an ounce per day, for man, inefficient; positive results were obtained only with 2 ounces per day.)
In order to learn the estimate placed on the therapeutic value of the “balsams,” an inquiry was sent to the authors of the papers presented to the section of Genito-Urinary Diseases at the recent meeting of the American Medical Association in New York. The inquiry read:
“Dear Doctor:—An advertising circular for Gonosan ‘Riedel’ which is now being distributed begins thus:
‘The old-established balsamic treatment of gonorrhea, for some years neglected in favor of the local injection of organic silver and other germicidal salts, has, with the increasing knowledge and attention paid to the composition and purity of the balsams, regained to a large extent the confidence formerly reposed in them.’
‘It may now be said that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy.’
“Is the statement correct that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy? Your reply to the above will be appreciated by the Council.”
Seventeen replies were received. They bear out the position that has been outlined. Only one writer considered the statement even approximately justified, and this in the sense that “the majority of cases receive no other treatment” than a combination of local applications and systemic medication. Another stated that, “in a general way their statement is true though a trifle too sweeping,” and then added that the field of the balsams is rather restricted. With the exception of these qualified endorsements the remaining (fifteen) replies characterized the statement as incorrect and misleading. The replies are a valuable contribution to the status of the “balsam” treatment of gonorrhea, and extracts of them are appended to this report.
It is recommended that the Council declare Gonosan inadmissible to New and Nonofficial Remedies, because the therapeutic claims are exaggerated (Rule 6); because there is no evidence that the combination of kava resin with oil of santal is superior to oil of santal alone (Rule 10); and because the therapeutically suggestive name is conducive of indiscriminate and unwarranted use of the preparation both by the profession and the public (Rules 4 and 8).
Appendix
The extracts from replies received to the inquiry above referred to, follow:
Dr. B., Penn., wrote:
“In my practice I have found that local injections are very valuable in the treatment of gonorrhea, but I have never found that the internal administration of natural balsamics dominated modern gonorrheal therapy; while it is an aid, I consider the quoted statement to be very erroneous.”
Dr. F., D. C., wrote:
“While it is doubtless true that acute urethritis, gonorrheal, is now generally treated by local injections of solutions of organic silver salts, and that santal oil is often used, it is not true, as one would infer from the quotation, that the balsams are now considered more efficacious than they were formerly. So far as I know they have not lost or regained anything during the past dozen years in the way of confidence reposed in them. The indications for their use is very definite and very limited.”
Dr. B., Ga., wrote:
“... In recent years I have almost abandoned the use of balsams, etc., in the treatment of gonorrhea. Patients, who are properly treated otherwise, seem to get along as well without such drugs as with them, in fact apparently better for they have no gastric disturbance. It is important for patients to drink freely of water and when so doing the balsams are so diluted that I cannot conceive of their doing much good. Formerly my patients often lost weight during the treatment of gonorrhea; now, without balsams and with plenty of water, they usually gain in weight.”
Dr. S., Mich., wrote:
“... we believe that in a general way their statement is true though a trifle too sweeping. We do not ordinarily use the balsams in uncomplicated anterior urethritis. We do however, find indication for their administration in from sixty to seventy five per cent. of all cases of acute gonorrhea at some time during the course of the disease.”
Dr. L., Mo., wrote:
“I would say that the statement that, ‘The combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy,’ is far from representing the facts. While the balsamics may occasionally have an indirect soothing effect on the mucous membranes involved, the dominant factor is local treatment, aiming at disinfection and restoration to normal of the inflamed tissues.”
Dr. R., Mich., wrote:
“Regarding your request although I am willing to reply it is difficult to do so because if I should do so in the affirmative that could apply only to certain acute cases without complication of any kind and such cases are rare. In such, however, the advertiser is not far from right—since vaccine therapy has proven absolutely worthless we must fall back on antiseptics in acute urethritis when there are no objections to such treatment ...”
Dr. K., Ill., wrote:
“I am under the impression that the internal administration of balsamics is used only when complications arise, such as acute posterior urethritis. Personally I use the balsamics very, very rarely. From my observation, however, I am led to believe that many men still use internal drugs in the treatment of gonorrhea, and during the past few years, I should say the use of hexamethylenamin has been on the increase, and the use of the balsams on the decrease. I do not believe that hexamethylenamin is of any value in the treatment of gonorrhea, and am simply citing this as my observation of the widespread use of this drug in the treatment of gonorrhea.”
Dr. T., Penn., wrote:
“... I believe that more men use salol or hexamethylenamin, or no urinary antiseptic whatsoever, than use the balsamics.”
Dr. B., Ind., wrote:
“... The only systemic treatment that is considered necessary today is rest, plenty of water and neutralize the acidity of the urine with bicarbonate of soda or some sodium salt.”
Dr. Y., Mass., wrote:
“Sandal wood oil during the acute stage of gonorrhea certainly tends to make the patient more comfortable and undoubtedly does lend some (tho I believe slight) gonococcidal action. That it plays any considerable part in actual cure I think is doubtful. The statement as quoted is true in so far as it states that local treatment plus internal medication with a balsam comprises most of the modern treatment of gonorrhea but it is grossly misleading in that it lets one draw the inference that the balsam plays a large if not the principal part.”
Dr. H., New York, wrote:
“For a period of at least three years in my hospital, dispensary and private practice, I conscientiously tried out most of the balsamics on the market (including Gonosan, which I favored for some time) both alone, and combined with local injections. As a result of this study, I have come to the conclusion that the balsamics have little, if any value in the treatment of gonorrhea. During the past few years I have relied almost entirely on local therapy, and seldom prescribed any of the balsams in my private practice, certainly in not more than 5 per cent. of the cases. My results I find are just as satisfactory, and my patients appreciate the fact that they are not loaded up with disagreeable medication. Instead of the balsamics, I am using sodium bicarbonate more and more, and feel convinced that the proper use of this drug is of more value than all of them combined.”
Dr. K., Cal., wrote:
“The statement that the combined treatment with local injections and internal administration of natural balsamic products completely eliminates modern gonorrheal therapy, would at present not be justifiable even with reference to the initial or acute stage of gonorrhea, while in the subacute and chronic forms of the disease local injections and balsams play an almost insignificant rôle as compared with various other recognized therapeutic measures.”—(From The Journal A. M. A., Oct. 13, 1917).
ALCRESTA IPECAC
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
In 1915 Alcresta Ipecac Tablets (Eli Lilly and Co.) were admitted to New and Nonofficial Remedies as a preparation of ipecac that is insoluble in the stomach but soluble in the intestines. It was supposed that this property would permit the administration of ipecac without the accompanying nausea and vomiting, and that this would be of especial advantage when using the drug in amebic dysentery. The systemic effects, of course, would be those of ipecac.
More recently, the manufacturers of Alcresta Ipecac have been advising its use in conditions which were not contemplated by the Council when the preparation was accepted for New and Nonofficial Remedies. They now claim that ipecac alkaloids have been shown to be useful in the treatment of typhoid fever, flatulence, diarrhea and constipation and that Alcresta Ipecac has these properties. Such a statement is misleading. While it is true that at one time ipecac was used promiscuously against “flatulence, diarrhea and constipation” there never has been and is not now any scientific evidence of its efficiency in such conditions except, of course, in diarrhea of the amebic type. As to the alleged usefulness of ipecac in typhoid fever: This has not even the sanction of tradition and the claim certainly should not be accepted until there is strong evidence to support it.
The advertising matter on Alcresta Ipecac also contained statements to the effect that ipecac alkaloids have a demonstrated usefulness in pyorrhea. Such an unequivocal statement is unwarranted. In spite of the enthusiastic advocacy, in the past, of ipecac alkaloids as a specific in pyorrhea alveolaris the preponderance of scientific evidence indicates that ipecac is of questionable value in this condition. Neither is there any substantial evidence to warrant the claim that ipecac alkaloids, when absorbed through the intestines, are demonstrably useful in amebic infections of the tonsils.
The reputation of the best drugs, whether unofficial or official, is bound to suffer if extravagant claims for them are permitted to go unchallenged. The referee of the Council, therefore, believed it necessary to call the attention of the manufacturers of Alcresta Ipecac Tablets to the statements made for the product and suggested that they submit evidence to substantiate the claims. This the manufacturers have refused to do. Their attitude in the matter, as well as their attitude toward the Council’s work is expressed in the following letter:
“Responding to your letter of March 10th, we beg to suggest that literature covering the different matters at issue are readily available to your referee, and all statements emanating from us are made advisedly.
“If you cannot satisfy yourselves that this preparation is a scientific product, ethically advertised, and a desirable advance in therapeutics, you can only delete it from your next issue of New and Nonofficial Remedies.”
It is to be regretted that Eli Lilly and Co. refuse either to withdraw or modify their claims or to substantiate these claims by scientific evidence. The statements as they stand are exaggerated, misleading and harmful. As such they conflict with Rule 6 of the Council and necessitate the omission of Alcresta Ipecac from New and Nonofficial Remedies. The referee recommended the adoption and publication of this report.—(From The Journal A. M. A., Oct. 20, 1917.)