Part 4

_Solubility of Salicin._—D. B. Dott (_Phar. Jour._, 1907, page 79) finds that the solubility of salicin, as given in the British Pharmacopœia (1 in 28) is practically correct, while that of the U. S. P. (1 in 21 at 25° C.) is too high.

Using pure salicin, that melted at 201° C., he finds that it has a solubility of 1 in 24 at 25° C., or very nearly that called for by the British Pharmacopœia at ordinary temperatures.

_Substitutes for Cocaine._—Dr. Hugo Wintersteiner (_Wiener Mea. Wochensch._, 1906, page 1339) reports a comprehensive comparative study of the use of cocaine and its various substitutes in eye work. Of the numerous substances that have been proposed from time to time he describes tropococain, holocain, eucain, stovain, alypin and novocain at some length and concludes that while it is true that these substances are relatively more stable than cocain, and are therefore more readily sterilized, the numerous objectionable features, such as unreliability, irritating properties and the production of a hyperemia, are so much more objectionable that cocaine must be admitted to be by far the most satisfactory as well as the safest local anesthetic in all varieties of eye work.

_Tannisol_ is a reddish-brown, odorless and tasteless powder that is insoluble in water, ether or benzine, but is soluble in alcohol and in dilute solutions of alkalies or of the alkaline carbonates. It is directed to be used internally in cases of intestinal catarrh, and externally for a variety of inflammatory conditions of the skin. Internally it may be given in doses of 0·50 gramme (_Phar. Centralh._, 1906, page 1006).

_Theolactin._—This name has been applied to a double salt of theobromin sodium and sodium lactate. It occurs as a white hygroscopic powder, readily soluble in water and having a distinctly bitter taste. It is said to be an active diuretic, but is not free from occasional side effects in the form of gastric disturbances. (_Phar. Zeit._, 1907, page 49.)

_Tinctura olea Europeae._—A tincture made with 60 per cent. alcohol from the dried leaves of the European olive has been used as a febrifuge as well as a general tonic in place of the tincture of cinchona bark.

_Triacetyl morphin._—This substance has been isolated from a mixture of acetyl derivatives of morphin. Triacetyl morphin melts at from 206 to 208° C., is only slightly soluble in water or cold alcohol, but is readily soluble in acids. With hydrochloric acid it forms a salt that crystallizes in the form of long needles. (_Phar. Centralh._, 1906, page 928.)

_Tulaselactin_ is the name given by Behring to a substance that is expected to immunize infants against tuberculosis. (_Phar. Centralh._, 1907, page 24.)

_Tulase_ (_A. J. P._, 1906, page 582) is the name given by Behring to his immunizing and curative serum for tuberculosis.

This preparation is said to contain all of the constituents of the Koch bacillus. It occurs as a clear fluid which has the general outward characteristics of thin honey. It may be given subcutaneously, intravenously or by mouth. The mixture of tulase with milk, mentioned above, is the form in which it may be administered to infants.

Tulase is now being used in an experimental way, but Behring himself warns against too much reliance being placed on the curative properties of the substance.

CORRESPONDENCE.

_Editor of the_ AMERICAN JOURNAL OF PHARMACY.

DEAR SIR:—I send you herewith the result of the votes of the Committee of Revision upon the first instalment of corrections in the U. S. Pharmacopœia, eighth revision, since the passage of the Food and Drugs Act.

Very truly yours, JOSEPH P. REMINGTON, _Chairman_.

CHANGES AND CORRECTIONS IN THE UNITED STATES PHARMACOPŒIA.

(Eighth revision.)

Belladonna Leaf _now_ 0·3 per cent. mydriatic alkaloids.

Belladonna Root _now_ 0·45 per cent. mydriatic alkaloids.

Colchicum Seed _now_ 0·45 per cent. of colchicine.

Ipecac _now_ 1·75 per cent. of ipecac alkaloids.

Stramonium _now_ 0·25 per cent. of mydriatic alkaloids.

Fluidextract of Belladonna Root _now_ 0·4 gramme alkaloids in 100 c.c.

Tincture of Belladonna Leaf _now_ 0·03 gramme alkaloids in 100 c.c.

Fluidextract of Colchicum Seed _now_ 0·4 gramme alkaloid in 100 c.c.

Tincture of Colchicum Seed _now_ 0·04 gramme alkaloid in 100 c.c.

Fluidextract of Ipecac _now_ 1·5 gramme alkaloids in 100 c.c.

Fluidextract of Stramonium _now_ 0·25 gramme alkaloids in 100 c.c.

Extract of Stramonium _now_ 1·0 per cent. alkaloids.

Tincture of Stramonium _now_ 0·025 gramme alkaloids in 100 c.c.

Jalap Root _now_ 7 per cent. of total resin.

Under the article Petrolatum, p. 336, U. S. P., last paragraph, the sulphuric acid test has been dropped.

February 15, 1907.

BOOK REVIEWS.

ELEMENTS OF GENERAL CHEMISTRY WITH EXPERIMENTS. By John H. Long, M.S., Sc.D., Professor of Chemistry and Director of the Chemical Laboratories in the Northwestern University Medical School. Fourth edition, revised and enlarged. Illustrated. Philadelphia: P. Blakiston’s Son & Co., 1906.

That Professor Long was more than justified in writing this textbook is shown by the fact that since the appearance of the first edition in 1888 two other editions have been issued, and it has been necessary now to issue a fourth edition. The time has gone by in all of the sciences when it can be said that a student is acquainted with fundamental principles unless he has repeated some of the classroom work in the laboratory. As Dr. Long well says: “Repetition is necessary to fix elementary principles thoroughly in the mind of the beginner.”

The present edition contains some additional matter on the theories of solution, the conditions of chemical equilibrium, some newer views of chemical theory and the description of several new substances. The book is a remarkably good one for the beginner, and is well adapted to the needs of the Freshmen class in any of the colleges where a general course in inorganic chemistry is given.

CHEMICAL ABSTRACTS. Published by the American Chemical Society. Vol. I, Nos. 1 and 2. Easton, Pa.: The Chemical Publishing Co. January 1 and 20, 1907.

Under this title the American Chemical Society has begun the publication of an independent semi-monthly periodical which shall furnish to American chemists at short intervals a full and comprehensive series of abstracts covering the whole range of pure and applied chemical science together with the titles of American, British, French and German patents on chemical subjects.

The importance and value of this undertaking can hardly be over-estimated. The Journal of the English Chemical Society has long covered somewhat similar ground, but hardly in the complete manner that our American society has now attempted; the Journal of the Society of Chemical Industry has always made a feature of its abstracts and patent references, but these cover applied chemistry only; the German Chemical Society some years ago took over the publication along with its _Berichte_ of the _Chemische Centralblatt_ for this same purpose of furnishing a complete series of abstracts, but it was felt that our American Chemical Society should take up this work for its own membership, now numbering over 3000 chemists.

So the Society for the future will publish its Journal as a monthly for original papers and communications, of which it has as many as it can possibly find room for in its twelve issues, and the Abstract Journal as a semi-monthly, covering the whole field of pure and applied chemistry under some 30 subdivisions, of which pharmaceutical chemistry is one. That this subject will be cared for in an appreciative and intelligent way can be assumed, as we note that Prof. A. B. Stevens of Ann Arbor is in charge of the abstracts in this field. For those who are not members of the Society the subscription price is as follows: Journal of the American Chemical Society, monthly, $6; Chemical Abstracts, semi-monthly, $6; for both journals sent to the same subscriber, $10. Members of the American Chemical Society receive both journals for the annual membership fee of $8.

S. P. SADTLER.

THE PHILADELPHIA BRANCH OF THE AMERICAN PHARMACEUTICAL ASSOCIATION.

The regular stated meeting of the Philadelphia Branch of the American Pharmaceutical Association was held on the evening of Friday, January 4, 1907, and was attended by 63 members and visitors.

The minutes of the previous meeting were read and declared approved.

The Committee on Sunday Closing and the Committee on State Legislation made preliminary reports that were received and ordered filed.

On behalf of the Committee on State Legislation Mr. Cliffe said that members of the committee had had an opportunity to confer with the members of a special committee of the State Legislature on the subject and that a joint conference of members of committees interested in the enactment of a State Food and Drug Law would be held at the Philadelphia College of Pharmacy on the evening of Tuesday, January 15, 1907.

The regular program for the evening was then proceeded with. This consisted of a discussion of “The Debasing Influences of Fraudulent Nostrums.”

The first communication, by Dr. Solomon Solis Cohen, was devoted to the consideration of “Secrecy and Fraud as Deterring Factors to the Progress of Medicine.” Dr. Cohen, in the course of his remarks, said that progress means an ascent from little or no knowledge to knowledge, and from knowledge to greater knowledge. Secrecy is the withholding of knowledge and breeds ignorance, while fraud is even worse than ignorance in that it is designed to mislead.

Dr. Cohen also asserted that therapeutics was difficult enough under the most favorable conditions and that in cases where a physician is confronted with secrecy or fraud, in the statements made in connection with medicinal preparations, he is likely to be misled himself and to do untold harm to his patients.

In concluding, the speaker referred to a number of specific preparations which have been discovered to differ materially in composition from what was claimed for them. He also expressed the hope that the Federal Pure Food and Drugs Law would be instrumental in leading manufacturers to more duly appreciate the need for a greater degree of honesty in the exploitation of their wares. If pharmacy is to make progress and if medicine is to make progress it will necessitate a full and complete knowledge of the composition and action of the substances used in the treatment of diseases.

The next communication, by Dr. Henry Leffmann, dealt with: “Known and Unknown Changes in the Composition of well-known Nostrums.”

Dr. Leffmann said that the question of secrecy was one of the most intricate problems and one that involved a number of factors.

Secrecy in connection with nostrums, the composition of which was known only to some one or more individuals, but not to all was an objectionable feature and frequently led to arbitrary and in many instances dangerous changes in the composition and the action of nostrums.

Dr. Leffmann then called attention to a number of specific instances in which it was known that changes had been made in the composition of widely advertised nostrums and also pointed out how these changes might be injurious to the consumer.

“Criminal Responsibility in the Sale of Abortifacients” was the subject matter of the communication by Dr. Henry Beates, Jr.

Dr. Beates referred to the various statutes relating to the use, sale or distribution of abortifacients and condemned, in no uncertain terms, the practice of advertising, in lay journals, articles designed to prevent conception or to produce abortion. He held that additional publicity might well be given to the serious nature of the questions involved, and urged that steps be taken to prevent the use of the United States mails by newspapers and magazines publishing advertisements of abortifacients or of instruments designed to prevent conception.

Dr. John B. Roberts, in opening the general discussion of the question, asserted that there certainly could be no difference of opinion on the degrading influences of practices that, as had been shown by the previous speakers, tended to convert pharmacists and pharmaceutical manufacturers into liars and medical practitioners into frauds and fakirs.

The subject matter was further discussed by Dr. Henry W. Cattell, Dr. F. E. Stewart, Dr. C. B. Lowe and Messrs. Remington, LaWall, Turner, Thum, Beringer, Vanderkleed, Cable, Westcott, Wilbert and Cliffe.

Mr. Cliffe presented the following resolutions, which, on motion, were unanimously adopted:

_Resolved_ that the Philadelphia Branch of the American Pharmaceutical Association condemns the advertisement in drug journals, magazines and newspapers of abortifacient medicines and deprecates their sale by reputable pharmacists.

_Resolved_ that all members of this branch be urged to exclude such medicines and articles from their stocks.

The secretary then read a communication entitled “Objectionable Side Lines to the Practice of Medicine,” specifically mentioning several profit-sharing and stock-distributing schemes that are now doing business in the city of Philadelphia.

This communication was, on motion, directed to be forwarded to the Secretary of the Philadelphia County Medical Society with the offer to submit additional evidence to the officials of that organization.

There being no further business the meeting was declared adjourned.

FEBRUARY MEETING.

The regular stated meeting of the Philadelphia Branch of the American Pharmaceutical Association was held on the evening of Tuesday, February 5, 1907, in the Hall of the College of Physicians.

The subject under discussion, “Higher Educational Requirements for Pharmacists,” has attracted considerable attention during the past year or more, and it was therefore not surprising to find that retail pharmacists attending this meeting were comparatively well informed on questions relating to education, and fully appreciated the need for more rapid advancement along educational lines in the future.

The first speaker on the subject, Mr. William L. Cliffe, in discussing “The Practical Needs for Higher Education in Pharmacy,” called attention to the fact that the people at large are rapidly becoming more thoroughly familiarized with the needs and the wants of the practice of pharmacy.

He believes that with the further elimination of empiricism and mysticism from the science of medicine more will be expected of pharmacists, and they in turn will be required to be educated in every way.

Prof. Henry Kraemer, in speaking on “Standards in Pharmaceutical Education,” (see p. 101) called attention to the fact that up to the present time the progress of pharmacy in this country had been comparatively slow and that we are now entering on an era of more rapid development. He believes that the enactment of pure food and drug laws will add great additional responsibility to the duties of the retail pharmacist and will also tend to more sharply define the corresponding duties of the colleges and of the boards of pharmacy.

Dr. Horatio C. Wood, Jr., in speaking on “The Future Elaboration of a Course in Pharmacy,” said that, as a commercial pursuit, the business of pharmacy must necessarily be one of limited scope and possibilities; as a profession, however, pharmacy can be developed into an occupation of laudable aims and high ideals. He believes that the pharmacist should develop as the assistant and the adviser of the physician, who in turn must depend more and more on the efforts of the pharmacist to select for him and to improve on the efficiency of the available articles of the materia medica.

Prof. I. V. S. Stanislaus, in opening the general discussion, gave it as his opinion that the pharmacist of the future would again hold the same relative position to the public as did the apothecary of old.

The pharmacist of the future will be the chemist of the people, the food and drug analyst, the assistant and adviser of the physician, in all matters relating to materia medica and chemistry, and will, therefore, practically be the sanitarian of the community.

The subject was further discussed by Messrs. John K. Thum, Franklin Apple, Jacob Eppstein, M. I. Wilbert, H. C. Blair, E. Fullerton Cook, John Hahn and Dr. F. E. Stewart. From the general trend of this discussion it was plainly evident that the better informed retail pharmacists deeply appreciate their responsibility to the public, and are willing and even anxious to meet their obligations fully. At no time in the history of pharmacy in this country has it been so evident that the mentally and morally poor man should not be allowed to jeopardize the health and even the lives of his fellow beings as now.

It is clearly evident that pharmacists are beginning to realize that a full and complete appreciation of their duties to society at large must of necessity react to their own pecuniary advantage and will in addition procure for them the respect and the admiration of their fellow men.

M. I. WILBERT, _Secretary_.

A REVIEW OF THE OPSONINS AND BACTERIAL VACCINES.[2]

BY E. M. HOUGHTON.

As requested by the _Therapeutic Gazette_, I shall attempt to describe as succinctly as possible the theory of the opsonins and the therapeutic results that have been obtained by the application of the new theory. As the years go by we realize more thoroughly the correctness of the prophetic belief of the “Immortal Pasteur,” that the day would come when it would be possible to eradicate the infectious diseases by vaccination.

We are indebted to Metchnikoff for calling attention to and explaining the rôle of the white blood cells in the defence of the body against bacterial invasion, but the phenomenon of phagocytosis is not so simple as it at first appeared, as little by little new facts are developed which amplify our knowledge of the subject.

It was shown by Denys and Leclef, in 1895, that when rabbits were immunized against _Streptococcus pyogenes_ the serum acquired but slight bactericidal properties, but that such serum, when brought in contact with the leucocytes of normal or immunized rabbits, greatly enhanced their phagocytic activity. Conversely no acceleration of phagocytosis was observed when the corpuscles were brought in contact with the serum of a normal animal.

Mennes two years later confirmed this by showing that similar results were obtained from the blood serum of guinea-pigs treated with cultures or toxins of Pneumococci.

A method of measuring the phagocytic activity of the leucocytes was developed by Leishman in 1902. In 1903 Wright and Douglas made an extensive study of the phagocytes, when brought in contact with suspensions of _Staphylococcus pyogenes_, and were able to show:

(1) Quoting from the original: “We have here conclusive proof that the blood fluids modify the bacteria in a manner which renders them a ready prey to the phagocytes. We may speak of this as an ‘opsonic’ effect (_opsono_ [a Latin verb], I cater for; I prepare victuals for), and we may employ the term ‘opsonins’ to designate the elements in the blood fluids which produce this effect.”

(2) Normal blood serum and plasma possess the same opsonic action upon bacteria.

(3) Serum loses its opsonic action when heated to 60° C. This is spoken of as inactivated serum.

(4) Inactivated serum and physiological salt solution have the same influence upon phagocytosis.

(5) “The opsonic power of the blood fluids disappears gradually on standing,” losing about 50 per cent. of its activity in five or six days.

(6) An anti-opsonic effect is noted when blood serum is digested with typhoid bacilli.

(7) When a condition of immunity is conferred upon patients infected by Staphylococci, by vaccination with heated cultures of Staphylococci, the opsonic action of the patient’s blood serum is greatly augmented.

Neufeld and Rimpau (1904) found in antistreptococcic and pneumococcic sera evidence of substances which, while inactive towards leucocytes, possessed very marked opsonic or sensitizing action, as they termed it, toward corresponding cultures of streptococci and pneumococci.

Ross (_Lancet_, November, 1906) summarizes our knowledge of the opsonins as follows:

“(1) Opsonins act by chemically uniting with the invading bacteria, and so altering them that the leucocytes are able to phagocyte the bacteria and destroy them. It is important to remember that these substances do not stimulate or otherwise affect the leucocytes.

“(2) It is probable that there are present many varieties of opsonins in the blood plasma, each having to do with combating a particular kind of microbic invasion.

“(3) Opsonins have been shown to be distinct from other bacteriotropic substances, such as the bacteriolysins, the agglutinins, and the antitoxins.”

The leucocytes of healthy or diseased persons seem to be equally active when brought in contact with the same serum, hence the amount of opsonins present in the blood of an individual determines, according to the opsonic theory, his susceptibility to bacterial invasion.

TECHNIQUE.

To measure the resistance of the patient to such invasion, or to find out his opsonic index, special technique has been developed, which may be briefly described as follows:

I. EMULSIONS OF BACTERIA.

Twenty-four-hour or younger growths of the rapid-growing bacteria, as Staphylococci, Streptococci, Pneumococci, Gonococci and Colon bacilli, upon inclined agar are washed off with normal saline solution. After the mixture has sedimented, the upper, whitish layer composed of fluid and bacteria is removed with a pipette, and the finer clumps of bacteria precipitated by placing the fluid in a rapidly rotated centrifuge for a few minutes. The supernatant layer, which is still opalescent and is called a bacterial emulsion, should if suitable for work contain the germs in a well-separated condition.

Cultures of tubercle germs are heated, and ground in a mortar with salt solution until the mass is well broken up, and then centrifugated. In case glycerin cultures are used, such as are left in the manufacture of Koch’s old tuberculin, the glycerin must be removed by repeated washing with water and finally with 1·5 per cent. salt solution. The washed culture is worked up in a mortar and centrifugated until the clumps are practically all thrown down, and the cloudy layer or emulsion is removed.

The emulsions must be of uniform density. Wright computed the number of germs in a given volume by counting, but McFarland and L’Engle devised an apparatus which is called a nephelometer, consisting essentially of mixtures of BaSO_{4}, put up in sealed tubes, which correspond to solutions containing from 1 to 10 per cent. of BaCl_{2}, which serve as standards. The turbidity of the emulsion is compared in similar layer with the standard tubes of BaSO_{4}. They found that the tube containing “5 per cent. of BaCl_{2} corresponds to the most useful bacterial suspension.” The permanency of the emulsions varies a good deal. Suspensions of the gonococci should be used at once, staphylococci within two days, etc., while the emulsion of tubercle germs may be employed indefinitely.

II. WASHED WHITE BLOOD-CORPUSCLES.