ARTICLES REFUSED RECOGNITION

PreparationPancreaticJuice Drops10 c.c. secretin2010 c.c. secretin digested with 0.5 c.c. gastric juice1510 c.c. secretin digested with 3 c.c. gastric juice1310 c.c. secretin digested with 10 c.c. gastric juice8

10 c.c. secretin

10 c.c. secretin digested with 0.5 c.c. gastric juice

10 c.c. secretin digested with 3 c.c. gastric juice

10 c.c. secretin digested with 10 c.c. gastric juice

* The digestive time was kept constant at fifteen minutes. (The gastric juice used had beendilutedwith stomach washings.)

The reader will observe in Table 1 that the results obtained from the control injection of secretin at the beginning of the experiment is uniformly greater than that obtained after several injections of digested secretin.

In view of the established fact that equal quantities of secretin can generally be relied on to produce results,62one might suggest that the injections of the split products of secretin have inhibited to some degree the action of the pancreas. We can submit the data in Table 3 in support of this view, showing among other things that the action of secretin is not influenced by previous injections of inert depressor substances, though it by the injection of the cleavage products of secretin. (The various injections in the experiments were made at about fifteen-minute intervals).

We have carefully analyzed the reaction in blood pressure that follows the injection of the various preparations. We find no constant effect. Digested secretin gives a fall in blood pressure that is at times less, at times equal, and at other times greater (Fig. 1) than that produced by the original preparation.

Besides the bearing that it has onthe therapeutic use of secretin, this destructive action of the digestive enzymes is also of prime physiologic interest. Failure to realize it has led to misconceptions as to the intrinsic nature of secretin.

TABLE 3.—EXPERIMENTS 8 AND 9

PreparationPancreaticJuice DropsExperiment 8:10 c.c. secretin, five injections of inert depressor substances2910 c.c. secretin, two injections of completely digested secretin2810 c.c. secretin, eight injections of inert depressor substances1610 c.c. secretin16Experiment 9:10 c.c. secretin (control, beginning of experiment)2110 c.c. secretin, after thirty minutes incubation with 1 c.c.boiledgastric juice2710 c.c. secretin, after thirty minutes incubation with 1 c.c.freshgastric juice1110 c.c. secretin (control, end of experiment)18

10 c.c. secretin, five injections of inert depressor substances

10 c.c. secretin, two injections of completely digested secretin

10 c.c. secretin, eight injections of inert depressor substances

10 c.c. secretin

10 c.c. secretin (control, beginning of experiment)

boiledgastric juice

freshgastric juice

10 c.c. secretin (control, end of experiment)

The findings of Lalou, confirmed by us, explain the anomaly that has ledDelezenne88to put forward the antisecretin theory.

It is a constant claim that so many and complex are the factors concerned in physiologic processes, that it is not unusual for clinical deductions to establish themselves in the face ofa priorilaboratory dicta. We considered it desirable, therefore, to test the action of secretin, orally administered, in the most direct manner, and the one freest from possible criticism. With this in view, we performed a series of experiments on normal unanesthetized dogs having permanent pancreatic fistulas.

Method.—In the operations for permanent pancreatic fistulas we followed closely the technic developed by Pawlow,89and with excellent results. The dogs maintain themselves in splendid condition if proper care is taken. This consists in feeding them only with bread and milk, and giving sodium bicarbonate daily. The dogs were given this treatment in the evening so that experimental procedure might be carried on in the day with empty stomach under constant conditions. Freshly prepared secretin in large quantities was given by stomach tube to these dogs, and the response of the pancreas studied and compared with the response obtained from control preparations. The same preparation was generally not given on consecutive days.

TABLE 4.—DETAIL OF TYPICAL EXPERIMENTS

Dogs with pancreatic fistulas, showing that secretin given by mouth has no action on the pancreas

Material Fed by Stomach TubeRate of Secretion of Pancreatic Juice in C.c. per Hr.Continuous SecretionBefore FeedingContinuous SecretionAfter FeedingFirstHourSecondHourThirdHourFirstHourSecondHourThirdHour150 c.c. active secretin, slightly acid6.53.63.920.06.08.0150 c.c. active secretin, slightly alkaline13.011.05.023.026.012.0150 c.c. secretin passed through Berkefeld7.87.57.423.013.011.0150 c.c. extract of colon11.612.011.430.019.614.8150 c.c. extract of gastric mucosa10.07.08.023.07.54.0150 c.c. extract of muscle6.911.06.435.05.07.0150 c.c. 0.4% HCl (diluted to 250 c.c.)6.08.04.033.036.017.0

150 c.c. active secretin, slightly acid

150 c.c. active secretin, slightly alkaline

150 c.c. secretin passed through Berkefeld

150 c.c. extract of colon

150 c.c. extract of gastric mucosa

150 c.c. extract of muscle

150 c.c. 0.4% HCl (diluted to 250 c.c.)

Results.—We have data from six dogs with a total of seventy-six experiments. As shown in Table 4, the administration of secretin causes an increase in the flow of pancreatic juice,butthe administration of inert substances asextracts of colon, gastric mucosa or muscle causes a like increase. The activity of the secretin may be reduced to a low value by exposure to sunlight, or filtering through a Berkefeld filter, yet the response of the pancreas is not correspondingly reduced. The secretion that occurs in the control cases, every one will admit, is but secondary to the production of gastric juice with its accompanying hydrochloric acid, that is, excited by virtue of the extractives and water in the preparations. Such, we can prove, is the only action of secretin. A mixture of gelatin, peptone and salt water, the chief incidental constituents of a secretin preparation, gives as striking results as ever obtained from secretin administration. Yet the objection may be made that the response of the pancreas that is due to the incidental constituents of secretin is maximal, and that the secretin consequently has no opportunity to display its particular potency. But, as inspection of the accompanying tables illustrate, the administration of hydrochloric acid shows that the response is by no means maximal. Let us cite a striking experiment. For three hours before the administration of hydrochloric acid, the secretion in cubic centimeters was respectively 29.4, 11.75 and 35.4 c.c.; for the three hours after, respectively 88.0, 49.0 and 40.5 c.c.

Fig. 1.—Tracings (reduced two-thirds) showing failure of Secretogen, Elixir Secretogen, and Duodenin to stimulate the flow of pancreatic juice even when administered intravenously in amounts three times greater than that recommended to be given by mouth. Dog: light ether anesthesia; cannula in the pancreatic duct;a, carotid blood pressure;b, flow of pancreatic juice in drops;c, signal showing where the intravenous injections were made. Tracing A: Reading from left to right, the five intravenous injections are: (1) three tablets of Secretogen digested with 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (2) three tablets of Secretogen boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Secretogen in 15 c.c. 0.9 per cent. sodium chlorid; (4) three tablets of Secretogen in 15 c.c. of 70 per cent. alcohol; (5) 15 c.c. Elixir Secretogen. Tracing B: reading from left to right, the four intravenous injections are: (1) 5 c.c. secretin made fresh from dog’s duodenal mucosa; (2) three tablets of Duodenin digested in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Duodenin boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (4) three tablets of Duodenin in 15 c.c. sodium chlorid (0.9 per cent.).

TABLE 5.—SUMMARY OF EXPERIMENTS

Dogs with pancreatic fistula, weight 14 kg. Secretin given by mouth

No. ofExperimentMaterial FedRate of Secretion of PancreaticJuice in C.c. Per HourIncreasein C.c.Three HoursBefore FeedingThree HoursAfter Feeding3Secretin slightly acid51165Secretin slightly alkaline243064Secretin passed through Berkefeld182351Secretin exposed to sun for 4 hrs1629132Extract of colon (rabbit)1929103Extract of gastric mucosa142393Extract of muscle81682Mixture of gelatin, peptone and salt23331011 per cent. peptone solution68240.2 per cent. hydrochloric acid1337243Milk and bread72013

Secretin slightly acid

Secretin slightly alkaline

Secretin passed through Berkefeld

Secretin exposed to sun for 4 hrs

Extract of colon (rabbit)

Extract of gastric mucosa

Extract of muscle

Mixture of gelatin, peptone and salt

1 per cent. peptone solution

0.2 per cent. hydrochloric acid

Milk and bread

It is possible by large doses of sodium bicarbonate given shortly before the administration of a preparation so to depress the stomach that it does not respond with the usual production of hydrochloric acid. Under these conditions the administration of secretin is uniformly negative, but the administration of hydrochloric acid on the contrary still serves to increase the pancreatic secretion (Table 6).

TABLE 6.—SECRETIN IN EXPERIMENTAL “ACHYLIA GASTRICA”

Exp.No.Material FedRate of Secretion of Pancreatic Juice in C.c. Per HourContinuous Secretion Before Feeding*Secretion After FeedingFirstSecondThirdFirstSecondThird1150 c.c. secretin8.77.56.83.01.04.824.56.510.06.07.57.6315.68.116.03.94.92.91150 c.c. 4% HCl (diluted to 250 c.c.)9.87.06.065.128.07.1217.418.517.034.018.020.0

150 c.c. secretin

* Five gm. Na HCO3given at beginning of each first two hours.

Secretogen and Elixir Secretogen.—The Carnrick Company offersSecretogen90for use in a large number of conditions. The following indications for the use of the preparation purport to be based on clinical tests covering a period of several years: dyspepsia, and the indigestions generally, fermentative disorders, gastric catarrh, flatulence, nausea; pancreatic insufficiency, intestinal indigestion; gastric secretory deficiencies, apepsia; constipation and hepatic torpor; intestinal stasis; diarrhea; infantile diarrhea, “summer complaint,” marasmus, inanition and malnutrition; gastric atony and dilatation; cholecystitis and gallstones; nephritis, neurasthenia, cachexia and cancer; epilepsy and high blood pressure. Testimonials are presented as to results in most of these conditions.

A quantity of “Secretogen” and “Elixir Secretogen” was bought in the open market, and the preparations were tested on suitably prepared dogs. The tablets were ground, thoroughly macerated with the solvent used (water, normal salt solution, alcohol, or 0.4 per cent. hydrochloric acid), and filtered. If hydrochloric acid was used, the pulverized tablets were boiled with it, in the manner that secretin is made from duodenal mucosa, and the preparations neutralized previous to injection. The injections were made in from 15 to 20 c.c. of the solvent. All the operations were carried on immediately before the experiment, and as rapidly as possible, so as to avoid oxidation. The Elixir Secretogen was injected directly, without dilution.

TABLE 7.—SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF SECRETIN IN “SECRETOGEN”AND “ELIXIR SECRETOGEN” EXCEPT IN OCCASIONAL TESTS WHEN ADMINISTERED IN ENORMOUS DOSES

Dogs under ether anesthesia

Exp.No.Quantity of Secretogen andElixir Secretogen Used*Secretion of Pancreatic Juice in Drops,Following Intravenous InjectionControl10 C.c.SecretinSecretogen inElixirControl10 C.c.SecretinDistilledWater0.4%HCl70%Alcohol0.9%NaCl1Secretogen, 1 tablet; Elixir, 15 c.c.10900000591Secretogen, 6 tablets.....0........2Secretogen, Elixir, 15 c.c. 3 tablets;1600001(?)163Secretogen, 5 tablets.....1(?)........4Secretogen, 25 tablets14..1(?)......85Secretogen, 100 tablets110......21..676Secretogen, 100 tablets; Elixir, 125 c.c.19..5..12(?)87Elixir, 50 c.c............1(?)..

Secretogen, 1 tablet; Elixir, 15 c.c.

Secretogen, 6 tablets

Secretogen, Elixir, 15 c.c. 3 tablets;

Secretogen, 5 tablets

Secretogen, 25 tablets

Secretogen, 100 tablets

Secretogen, 100 tablets; Elixir, 125 c.c.

Elixir, 50 c.c.

* One to three tablets is (according to the label) the therapeutic dose of Secretogen; 4 to 12 c.c. the dose of Elixir Secretogen.

Results.—In only one case was a slight response obtained, the others gave none. Small and large doses were equally inert (Table 7, Figs. 2, 3). The preparations, though inert, always produced a depression in blood pressure, sometimes even greater than that caused by active secretin. Among our many tests, one bottle was found, however, to be a little different from the rest (Experiment 4). Its entire content, 100 tablets, had been ground and boiledin 0.9 per cent. sodium chlorid. The extract on injection was found to have a small but unmistakable secretin reaction, equivalent to about 2 c.c. of the control secretin used. But repeated experiments were unable to duplicate this result. The “Secretogen” and “Elixir Secretogen” were all supposedly fresh preparations, the retail drug store informing us that a fresh supply was obtained from the wholesale house each week.

Secretogen, then, contains practically no secretin, and even if it did contain secretin, it can have no effect on the pancreas when taken by mouth. The indications for Secretogen, therefore, are based on false premises, and the testimonials are worthless.

Fig. 2.—Tracings (reduced one-half) showing no stimulation of the pancreas by Secretogen, Elixir Secretogen, and Duodenin, even when administered intravenously in quantities one hundred times greater than the therapeutic dose by mouth. Dog: Light ether anesthesia; cannula in the pancreatic duct;a, carotid blood pressure;b, flow of pancreatic juice in drops. Tracing A: atx, intravenous injection of 10 c.c. secretin prepared from duodenal mucosa of dog. Tracing B: atx, intravenous injection of 100 tablets of Secretogen digested with 0.4 hydrochloric acid and neutralized. Tracing C: atx, intravenous injection of 100 tablets of Secretogen, prepared as in Tracing B. Tracing D: atx, intravenous injection of 50 c.c. Elixir Secretogen. Tracing E: atx, intravenous injection of 100 tablets of Duodenin (dissolved in 0.9 per cent. sodium chlorid).

Duodenin.—This is a preparation manufactured by Armour & Company, which purports to be “secretin plus enterokinase.” The claims for this product are similar to those for Secretogen, but somewhat less sweeping. According to the manufacturers, “Duodenin (Armour) is recommended in the treatment of intestinal disorders where an increased flow of pancreatic, hepatic and intestinal secretion is desired. It is of specific value in proteid digestion on the theory that secretin and enterokinase stimulate the pancreas and activate its secretion.”

Fig. 3.—Tracings (reduced one-half) showing practically complete destruction of secretin by the gastric juice. Dog under light ether anesthesia; cannula in the pancreatic duct;a, carotid blood pressure;b, record of flow of pancreatic juice in drops. Time, twenty-five minutes. Tracing A: intravenous injection of 10 c.c. secretin (prepared fresh from dog’s duodenal mucosa) atx. Tracing B: intravenous injection (atx) of 10 c.c. of the same secretin as in Tracing A, after being digested in normal human gastric juice at 37 C. for two hours.

We bought a quantity of Duodenin in the open market, and carried out on this product the same series of experiments as that used in the case of Secretogen. The results were similarly negative (Table 8).

TABLE 8.—SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OFSECRETIN IN “DUODENIN”

Dogs under ether anesthesia

Exp.No.NumberDuodeninTabletsUsedSecretion of Pancreatic Juice in Drops,Following Intravenous InjectionControl10 C.c.SecretinDuodenin inControl10 C.c.SecretinDistilledWater0.4%HCl70%Alcohol0.9%NaCl13290001(?)2816.....1(?)......21816..6....163514..0008325.....1(?)......4100110..0....67515019..0..08

In regard to both Secretogen and Duodenin, we assume that the manufacturers have tried to put secretin in them, but have been unable because they have failed, in all likelihood, to check their methods by physiologic standardization. These firms do not give any details as to the procedure they employed in their manufacture of secretin. Desiccated secretin of extreme potency has been prepared by various physiologists,911 mg. (1⁄64grain) of which is active when given intravenously. It is difficult to conceive that any of these methods were used in the preparation of Secretogen or Duodenin.

1. Secretin is quickly destroyed by gastric juice and by trypsin.

2. Secretin is not absorbed in active form from the alimentary tract.

3. The presence of secretin or prosecretin cannot be demonstrated in the commercial preparations “Secretogen,” “Elixir Secretogen” and “Duodenin” even when the therapeutic dose of the preparations is given intravenously. In the case of “Secretogen,” intravenous injection of 100 times the therapeutic dose reveals occasionally an insignificant trace of secretin.

It is, of course, objectionable that preparations containing no secretin should be advertised to the medical profession as containing this substance. The more important blunder, however, consists in the attempt to offer such preparations for oral administration, because even chemically pure secretin would be equally ineffective when taken by mouth. There is as yet no reliable evidence that lack of secretin is a primary or important factor in any disease. Even should this be established, secretin therapy, to be effective, must be intravenous. Secretin has not yet been prepared in sufficiently pure state to render possible intravenous injection in man without injurious effects. And even when this has been attained, the very fleeting action of secretin will in all probability render secretin therapy as futile in all the diseases in which it is theoretically indicated as epinephrin therapy is in Addison’s disease.

But there remains the alleged favorable effect from secretin therapy by mouth in various diseases in man. It is, perhaps, impertinent for laboratorymen to comment on these clinical results. The ordinary “testimonials” need not be considered, but we should like to ask the serious worker who thinks he has actually obtained good results from secretin therapy how certain he is of the causal relation between the giving of secretin or alleged secretin and the abatement of the disease.

When a therapeutic measure not only lacks a positive basis in physiology and pathology but runs contrary to all the well-established experimental facts in these fundamental medical sciences, is it too much to ask that positive clinical findings be subjected to more than usual critical analysis before acceptance? “Clinical tests,” it is said, “covering a period of several years have proved that neither the condition in the stomach during digestion nor those in the intestine prevent the secretin from entering intact into the circulation.” When we meet claims such as this, should we not scrutinize the “tests” as well as the men who make them?

We are indebted to Dr. J. H. Moorehead for assistance in part of the surgical work.—(From The Journal A. M. A., Jan. 15, 1916.)

Below appear abstracts of the Council’s action on articles refused recognition which were not deemed of sufficient importance to require lengthy reports:

The Radium Therapy Company, Schieffelin & Co., selling agents, submitted to the Council radium emanation generators called “Radio-Rem Outfits,” designed to generate respectively 200, 1,000, 2,000, 5,000 and 10,000 Mache units per twenty-four hours.

Those who are well informed on the subject of radium therapy are of the opinion that the administration of small amounts of radium emanation such as generated by certain outfits is without therapeutic value. It has been stated that at the Radium Institute of London the minimum preliminary dose is 185 microcuries (500,000 Mache units), and as many as 555 microcuries (1,500,000 Mache units) are employed.

In consideration of these facts the Council voted not to accept any radium emanation generator which produces less than 2 microcuries of emanation during twenty-four hours. Accordingly, while accepting Radio-Rem Outfit No. 5, claimed to produce 10,000 Mache units (3.7 microcuries) and Radio-Rem Outfit No. 4, claimed to produce 5,000 Mache units (1.8 microcuries), the Council voted not to accept Radio-Rem Outfit No. 3, claimed to produce 2,000 Mache units (0.74 microcurie), Radio-Rem Outfit No. 2, claimed to produce 1,000 Mache units (0.37 microcurie), and Radio-Rem Outfit C, claimed to produce 200 Mache units (0.07 microcurie).

This report having been submitted to Schieffelin & Co. and their reply considered, the Council authorized publication of the report. [See alsoReports of Council on Pharmacy and Chemistry, 1916, p. 631.]

Olio-Phlogosis, a liquid preparation to be applied externally by means of a cotton pad, is advertised by the Mystic Chemical Company, Kansas City, Mo., thus:

“Doctor: Don’t fail to use Olio-Phlogosis liberally for Pneumonia, Bronchitis and Pleurisy. It works quickly. Olio-Phlogosis is as far ahead of all medicated kaolin plasters as these plasters were ahead of the old-time moist and soggy poultices.”

A pamphlet advises the use of Olio-Phlogosis in

“... all cases of Inflammation and Congestion, such as Pneumonia, Bronchitis, Pleurisy, Croup, Boils, Carbuncles, Rheumatism, Swollen Glands, Peritonitis, Ovaritis, as a Surgical Dressing, Mamitis [Mastitis (?)] Vaginitis and Metritis (on cotton tampon to deplete these parts), Septic Wounds, Old Ulcers, Chilblain, Eczema, Neuralgia, Inflammation of the Eyes and Ears, Alveolar Inflammation, Burns, Scalds, Etc.”

According to the information sent to the Council by the Mystic Chemical Company, Olio-Phlogosis has the following composition per gallon:

Ol. Eucalyptus Gaultheriadrs.8Ol. Abies Canadensisdrs.8Ol. Abies Canadensisdrs.2Ol. Thyme (white)drs.2Resublimated Iodin crystalsgrs.32Resorcindrs.1Acid Boracic C. P.drs.2Quinine Bisulphatedrs.4Sodium Thiosulphatedrs.31⁄2Glycerin C. P.q. s. adgal. 1

Ol. Eucalyptus Gaultheria

Ol. Abies Canadensis

Ol. Thyme (white)

Resublimated Iodin crystals

Resorcin

Acid Boracic C. P.

Quinine Bisulphate

Sodium Thiosulphate

Glycerin C. P.

A nonquantitative formula which appears on the label of a sample bottle sent to a physician enumerates the same ingredients except the sodium thiosulphate.

The A. M. A. Chemical Laboratory reports that no free iodin could be detected in the preparation.

Apparently, then, Olio-Phlogosis is essentially a skin irritant applied by means of cotton; it can be expected to be just about as effective as the old-fashioned cotton pneumonia jacket, used in conjunction with an aromatic skin irritant, such as camphorated oil or wintergreen or menthol ointment. The odor may have some psychic effect, and it is possible that some of the oily matter may be absorbed by the skin. That such small amounts, even if absorbed, can produce any considerable systemic effect, however, is highly improbable, and the advice that this preparation be relied on in pneumonia, pleurisy, peritonitis, etc., is pernicious. In the few cases of pneumonia in which heat is indicated, the plain cotton pad will usually be found sufficient. If the physician consider the addition of a skin irritant desirable, it is easy to select one from the official preparations. It will be far more rational to do so than to invoke the aid of a mystic name and a complex formula to which the patient and his family, at least, will be led to give unmerited credit.

The claims made for Olio-Phlogosis are unwarranted; its composition is complex and irrational, and the nondescriptive but therapeutically suggestive name is likely to lead to uncritical use. The Council voted that the product be refused recognition for conflict with Rules 6, 8 and 10, and that this report be published.—(From The Journal A. M. A., Aug. 19, 1916.)

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

The introduction of hypophosphites into medicine was due to an erroneous and now discarded theory as to the cause of tuberculosis of which one Dr. J. F. Churchill of London, and later of Paris, was the promulgator and propagandist.92This theory was that the so-called “tuberculosis diathesis” was due to a deficiency of phosphorus in the blood. Believing that the hypophosphites, while nontoxic, were capable of further oxidation in the organism, Churchillrecommended them as the best means of supplying the supposedly lacking phosphorus. It is now known that tuberculosis is not due to a deficiency of phosphorus. Of more importance is the fact, now known, that little phosphorus, if any, is assimilated from the hypophosphites—far less than from phosphorus compounds of ordinary food.93There is no justification for giving hypophosphites for the sake of their phosphorus content. For various reasons, however—partly from force of habit and partly because of the power of advertising—many physicians still prescribe hypophosphite preparations, and consequently, they are still included in the Pharmacopeia and in textbooks on materia medica and therapeutics. They are put out in the form of “specialties” and of proprietary preparations, and are lauded extravagantly by the manufacturers of the latter.

Although the overwhelming weight of evidence was against the probability that the hypophosphite preparations are of value as therapeutic agents, the Council thought it well to investigate the subject. Dr. W. McKim Marriott of Baltimore was therefore requested to review the evidence for and against the therapeutic usefulness of the hypophosphites and to conduct such experiments as seemed necessary. His report has already appeared inThe Journal.94

Dr. Marriott found that nine observers (Paquelin and Joly, Vermeulen, Boddaert, Massol and Gamel, Panzer, Delaini and Berg), who endeavored to test the alleged utilization of the hypophosphites in the organism, reported that there is complete, or practically complete, elimination of hypophosphites in the urine, with little or no effect on the body. Only one experimenter (Patta) claimed that a considerable amount of ingested hypophosphite was retained in the body; however, he used a method now known to be inaccurate and made obvious errors in calculation, so that his conclusions were unwarranted.

Since the evidence was even to this extent contradictory, Marriott performed a series of experiments. The methods of this study and details of results are described in his paper, in which he also discusses the experiments of some other observers. Marriott writes:

“None of the subjects of the experiment [Marriott’s] experienced any effect whatsoever from the administration of the drug.... Almost all of the ingested hypophosphite is promptly eliminated unchanged....“These experiments [Forbes’] demonstrate conclusively that the hypophosphites possess no specific value as a source of phosphorus for the body. This is not to be wondered at in view of the fact that 85 per cent. of the phosphorus ingested in the form of hypophosphite is excreted unchanged, and there is no proof that even the remaining 15 per cent. is available to the organism. It is doubtful if there are any conditions in which the body suffers from lack of phosphorus. Even should such conditions exist, phosphorus, in the form that it occurs in the ordinary foods, or as phosphates, is more efficient in supplying the deficit than hypophosphites that must be oxidized before utilization and which are only about 15 per cent. oxidized, if at all. For example, half a glass of milk contains more available phosphorus than three large doses of hypophosphites of 15 grains each, as great a dosage as is usually given.“What, then, is the therapeutic value of hypophosphites? There is no reliable evidence that they exert a physiologic effect; it has not been demonstrated that they influence any pathologic process; they are not ‘foods.’ If they are of any use, that use has never been discovered.”

“These experiments [Forbes’] demonstrate conclusively that the hypophosphites possess no specific value as a source of phosphorus for the body. This is not to be wondered at in view of the fact that 85 per cent. of the phosphorus ingested in the form of hypophosphite is excreted unchanged, and there is no proof that even the remaining 15 per cent. is available to the organism. It is doubtful if there are any conditions in which the body suffers from lack of phosphorus. Even should such conditions exist, phosphorus, in the form that it occurs in the ordinary foods, or as phosphates, is more efficient in supplying the deficit than hypophosphites that must be oxidized before utilization and which are only about 15 per cent. oxidized, if at all. For example, half a glass of milk contains more available phosphorus than three large doses of hypophosphites of 15 grains each, as great a dosage as is usually given.

“What, then, is the therapeutic value of hypophosphites? There is no reliable evidence that they exert a physiologic effect; it has not been demonstrated that they influence any pathologic process; they are not ‘foods.’ If they are of any use, that use has never been discovered.”

In view of the foregoing, it seemed to the Council advisable to examine the claims under which a few of the proprietary hypophosphite preparations are marketed. The following are representative:

No very exact information concerning the composition is furnished by the manufacturers (Fellows Medical Mfg. Co., New York). They say that the product

“... contains the chemically pure hypophosphites of iron, quinin, strychnin, calcium, manganese and potassium, agreeably blended in the form of a bland, stable syrup with a slightly alkaline reaction....“Each fluid drachm contains the equivalent of 1-64th of a grain of pure strychnin.”

“Each fluid drachm contains the equivalent of 1-64th of a grain of pure strychnin.”

The Fellows’ Hypophosphites advertising furnishes something like a barometer of the popular status of hypophosphites. In one circular (undated, but, from certain references contained in it, presumably issued ten or fifteen years ago) we read:

“It is an indubitable fact that the hypophosphites have earned the distinction of having their therapeutic value more completely established than have any other remedial agents.... it is only by accepting the current view, which was originally advanced by Mr. Fellows, that we can satisfactorily account for the incontestable fact that the hypophosphites are of supreme importance in the treatment of a very extensive variety of affections.... the hypophosphites increase the consumption of oxygen and the elimination of carbon dioxide. In this manner, they stimulate nutrition and promote constructive metamorphosis.... It is now universally conceded that the widespread utility of the hypophosphites is due to the fact that they substantially improve metabolic processes, thus increasing the disease-resisting capacity of all the tissues.”

The circular, continuing, emphasizes the “incomparable phosphorus-contributing properties” of Fellows’ Syrup, its “extraordinary reconstructive properties” and “the magnificent results which invariably attend its employment in the treatment of anemia, chronic bronchitis, chlorosis, neurasthenia, mollities ossium, delayed union of fractures, rickets, convalescence,” etc.

A circular bearing the copyright date 1914, on the other hand, admits that:

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