by the pressure of the fluid may be utilized. Our practice has been to determine upon a suitable dose for a particular animal and dilute this more or less according to the character of the operation, rather than to depend upon any strength solution. A small amount of a weak solution is sufficient for endoneural work but for perineural injections a stronger one is preferred. Schleich's strongest solution for infiltration anesthesia contained 0.2 per cent of cocaine hydrochloride. A 0.5 per cent solution is strong enough for many operations.

Duration of action. Cocaine produces anesthesia very promptly but is absorbed so rapidly that its action is comparatively brief. A small amount of adrenaline added to the anesthetic will delay the absorption and thus prolong the anesthesia, lessen toxic action and at the same time render the operation almost bloodless. This statement holds good with the substitutes.

Cocaine substitutes. Cocaine is not the ideal anesthetic for many reasons. It is toxic, does not stand sterilization by boiling, is not stable in solution, and there is an occasional idiosyncrasy to it. In order to overcome some of these disadvantages numerous closely allied synthetic substitutes have been prepared. They are employed in the same way as cocaine. The most common of the substitutes are eucaine, stovaine, alypin, procaine, apothesine, tropococaine, quinine and urea hydrochloride. All resemble cocaine in action but are generally regarded as weaker. A few of the differences of the more important ones will be pointed out.

Alypin is irritant to tissues, stands boiling not to exceed five minutes without decomposition, dilates instead of constricting the capillaries, dilates the pupils and is claimed to be less toxic. The evidence concerning its toxicity is conflicting. It is generally claimed to be one-half as toxic as cocaine but this does not seem to hold in cases of horses at least, because many practitioners have reported verbally that they used large amounts without any symptoms of poisoning. Eggleston and Hatcher found alypin onethird more toxic than cocaine for cats but based their figures on rapid intravenous doses.

Eucaine or beta eucaine hydrochloride is somewhat weaker than cocaine but does not have the stimulating properties of that drug. It does not affect the capillaries or pupil. Its main advantage is that it can be boiled without decomposition.

Holocaine resembles cocaine but is much more rapid and at the same time has an antiseptic action. Its action, however, is very brief. Holocaine is chiefly used in ophthalmology. A 1 per cent. solution will produce anesthesia in from one to ten minutes.

Procaine formerly called novocaine is one of the more recently introduced substitutes. It is much less toxic than cocaine, is a powerful anesthetic but of a short period of action unless used

with a powerful constrictor to prevent its absorption. It is not active when applied to sound mucous membranes because it is not absorbed from them. Procaine is less toxic than alypin or stovaine.

Stovaine is about as strong an anesthetic as cocaine but dilates instead of constricting the blood vessels. It is too irritant for use in the eye and has a tendency to cause gangrene at the site of injection. Stovaine is generally given as about one-third as toxic as cocaine.

Apothesine. This is one of the newer products. It is claimed to be as efficient as any of the other members of the group, to be free from irritation, less toxic and more stable in solution than cocaine.

Apothesine is also somewhat slower. but more persistent in action. We have used this agent for many operations upon the small animals and have found it very satisfactory.

Quinine and urea hydrochloride is slow but persistent in action. It is reported that the anesthesia may last for several days. The long period over which anesthesia persists makes this agent extremely valuable in ophthalmology, or in other conditions in which the prolonged anesthesia is of advantage. The usual strength solution is from 2 to 4 per cent for subcutaneous injection, although some claim that solutions stronger than 0.25 per cent prevent healing. For mucous membranes much stronger solutions, 10 to 20 per cent, must be employed.

Butyn is a new product. It is claimed to be more rapid, more lasting and more efficient than cocaine. It does not dilate the pupil or irritate the eye, is antiseptic and may be sterilized by boiling. Butyn is particularly efficient for surface anesthesia, a 0.5 per cent solution is said to be more efficient than a 1 per cent solution of cocaine for surface anesthesia. On the other hand, it has been found 212 times as toxic for albino rats when administered hypodermically. The favorable reports of its use in eye, ear, nose and throat surgery indicate that it will be a valuable addition to veterinary medicine.

COMPARISON OF COCAINE AND ITS SUBSTITUTES

Cocaine is the oldest and best known anesthetic. It produces its action promptly and with certainty, constricts the arterioles, may be used as a mydriatic, does not irritate and is active upon sound mucous membranes. The substitutes improve upon the older drug by being more stable in solution, stand sterilization by heat, are less toxic and the best substitutes, procaine and apothesine, do not come under the narcotic law.

Practically all manufacturers claim their product is less toxic than cocaine and some interesting work has been done in this direction. Eggleston and Hatcher give the following table for

comparison. The figures represent the minimum fatal dose in mg. per kg. of body weight of cats.

These doses are really misleading because they represent intravenous doses rapidly given. They found that cats could stand 5 or more than 5 times the minimum fatal doses when the drugs were administered subcutaneously with the exception of cocaine and holocaine, in which case 4 or less than 4 times the minimum dose proved fatal. They further determined that the toxicity depended upon the ratio between absorption and destruction or elimination, and could be materially reduced by the simultaneous injection of epinephrine. With the exception of cocaine and holocaine the elimination keeps pace with the absorption so that comparatively large doses may be given at short intervals without injury to the animal. In the case of cocaine, the destruction may be so slow that repeated doses may lead to cumulative action. This is shown nicely in an experiment by Grode who tried to habituate both dogs and cats to repeated doses of cocaine. He noticed increased susceptibility to fixed hypodermic doses when these were made at intervals of a day or two. For instance, to one cat to which he planned to give 20 mg. per kg. of weight of cocaine daily, the first dose caused salivation, the second emesis, the third three tetanic spasms, the fifth eight spasms, then a twoday interval between the sixth and seventh doses but the seventh dose caused repeated spasms and the eighth on the next day was fatal. It is possible that this increased susceptibility is responsible for some of the unexpected results from the administration of ordinary doses to race horses.

REFERENCES

New and Non-official Remedies, 1919, p. 26.

SOLLMAN, T. A Manual of Pharmacology, p. 251.

BASTEDO, W. A. Materia Medica, Pharmacology and Therapeutics, 2nd Ed., 1919, p. 412.

EGGLESTON, CARY AND HATCHER. Jour. Pharm. and Exp. Therap., Vol. 13, 1919, p. 433.

GRODE, JULIUS. Arch. Exp. Path and Pharm., 1912, LXVII, p. 122. Quoted by Eggleston and Hatcher.

Report of Council on Pharmacy and Chemistry, Jour. A. M. A., Vol. 77, N. 24, p. 189, Dec. 10, 1921.

A STUDY OF SOME FACTORS INFLUENCING FERTILITY AND STERILITY IN THE BULL

HERBERT L. GILMAN

Veterinary Experiment Station, Cornell University

Normal reproduction is the fundamental foundation upon which the entire cattle industry rests. For this reason, any factor capable of interfering with it is a detriment to the industry, and a matter of prime importance to the breeder and the veterinarian. With the relative increase in number and value of cattle, and the fact that the profession is depending more and more on this industry for a livelihood, these problems are assuming greater importance. The part played by the bull has been emphasized entirely too little, with the result that, as in human medicine, many fail to appreciate the effects of sterility or lowered fertility in the male. The part played by the sire in the spread of genital infections, though discussed frequently, has received little systematic investigation.

The bull must be regarded as at least half the herd, not only from the standpoint of the characters he imprints upon his progeny, but because of his relation to the reproductive efficiency in the herd. It seems quite probable that he does disseminate during copulation, infection associated with the genital organs, with the result that the bull is a very important factor in a study of the subject. Too frequently, his ability to copulate in an apparently normal manner, is taken as a standard of fertility. Gross changes in his genitalia, or the absence of spermatozoa from the semen are given due consideration, while other more obscure abnormalities are not looked for nor regarded in their proper light. Neither fertility nor sterility are always absolute, but the terms should be used relatively inasmuch as we may have all degrees of infertility or impotency. All too frequently we forget the many delicate and intricate mechanisms involved in the reproductive process, with the result that many phases of the problem are neglected or disregarded. The genital organs work as a unit, each part of which must function in perfect accord with the others to the end that full fertility may result. The physiological factors involved in the formation of the semen are too little understood, or at best, our knowledge regarding them is more or less hazy.

The purposes of the present work have been: (1) to summarize the work so far done on the subject, (2) to review briefly the known facts throwing light on the anatomy and physiology of the male genital organs, (3) to carry out systematic studies upon the pathology and bacteriology of the genital tract of the bull, and (4) to ascertain if possible whether the bull is a disseminator of those infections which interfere with reproduction in the female.

The work has been carried on for the most part from the point of view of a laboratory man cooperating with clinicians. No attempt is made in this paper to give detailed clinical data, methods for physical examinations, etc. There are included many statements and some data given in a preliminary article on the subject. While the subject is broad in its scope, in fact too broad for great detail, it is hoped that a start has been made toward future and more detailed investigations.

HISTORY

References to, and investigations relating to, the part played by the bull in the process of reproduction in the herd, and in the spread of genital infections, have been limited largely to those phenomena caused by Bact. abortum. Bang (1) originally called attention to the possibility of the male transmitting the organism discovered by him, but he reached no definite conclusion on the subject. James Law (2) writing on contagious abortion in cows, early suspected this possibility when stating under "casual infections," that " In a case which came under the observation of the writer recently, a family cow, kept in a barn where no abortion had previously occurred, was taken for service to a bull in a herd where abortion was prevailing, and though she was only present at the latter place for a few minutes, she aborted in the sixth month." Jansen, as quoted by Sand, reports the case of a cow from an aborting herd having been taken into a herd that had been previously quite free from the disease. Soon after her arrival she aborted, and later cow after cow of the original herd aborted. The owner kept the matter a secret, and sent his cow to a neighbor's bull for service, with the result that for two years abortion prevailed among cows served by this bull. McFadyean and Stockman (3) later, in experimental work, attempted but failed to infect cows by using a soiled bull for service. Hadley and Lothe (4) state: "A large number of stockmen hold that the bull is an important factor in the transmission of contagious abortion in herds. A smaller number believe that the bull merely acts as a passive carrier of the abortion disease and is not actively concerned in the transmission." In a subsequent bulletin, Hadley (5) remarks: "The abortion organisms may enter the body during sexual intercourse." In an experiment carried on by the same author and co-workers, abortion-free virgin heifers were mated to abortion-infected bulls, infection being, evidenced by positive. reactions to the complement fixation and agglutination tests. His results indicate, he believes, "that the bull is not so important a factor in transmitting abortion as many believe." The conclusions are: "Bulls may become infected with abortion bacilli. Bulls that reacted to the blood tests were incapable of disseminating the abortion disease to the abortion-free heifers with which they were mated. Bulls appear to possess a sexual or individual immunity to abortion infection that renders them less susceptible

.....