by a portion of the stomach could be separated from the rest without disturbing its nerve or blood supply, so that when food was administered to an animal the substances introduced into the stomach entered only a portion of it, leaving a cul de sac open to observation, and wholly free from foreign materials or other disturbing elements. It was thus found possible, by feeding the animal different substances, to ascertain the exact influence of these substances upon pepsin secretion and acid formation.

In the preparation of an animal for experiment, it is first given a large meal, by which means it is found that all the pepsin formed was forced out of the mucous membrane and consumed in the digestion of the blood, so that the stomach was completely aseptic at the beginning of the experiment some hours later. We have not space to recount the details of the experiments made by Pawlow, Herzen, Radzikowsky, and others; it is sufficient to give the results. It was found that there are three classes into which food substances or elements may be divided:

I. Those which promote pepsin formation. The common or yellow dextrin of commerce-not the white variety, which is practically inert-possesses the power of stimulating the stomach to secrete pepsin to a most remarkable degree, increasing the quantity of pepsin from five hundred to six hundred per cent.

2. Substances which promote the secretion of acids. Liebig's extract of beef was found to possess this property in a very high degree

3. Substances which promote both the secretion of pepsin and the production of pepsin and the production of acid. The chief of these were raw meat, meat juice, meat broth, and pease broth.

The practical deductions from these experiments are of the highest importance and have been proved, by actual experiment, to be reliable. Let us notice some of these: First, in relation to hyperpepsia or hyperchlorhydria: This condition is one

which has been the occasion of no small amount of inconvenience to physicians as well as to patients. The custom of confining these patients to an almost exclusive meat diet has long prevailed, but without satisfactory results; the patient is temporarily relieved, but not permanently cured. The writer has had under observation scores of cases of this sort, in whom the exclusive meat diet had been faithfully carried out for months without any curative results whatever, the only tangible effect being to render the patient more and more dependent upon the use of soda and magnesia as neutralizing agents, and making him a complete slave to his meat diet through a continued increase of acid formation. What the hypopeptic patient requires is a dietary which will increase the formation of pepsin. This will render possible the utilizing of the large amount of acid formed, which may then become a means of promoting his welfare instead of being a source of distress and injury. It is impossible to suppose that a person would actually suffer from the secretion of excessive gastric juice in conection with the meal, provided the latter were normal in character. That the gastric juice formed in hyperpepsia or hyperchlorhydria is not a normal secretion, however, is made very apparent by the facts developed through a careful study of the gastric secretion by the accurate and refined method devised by Hayem and Winter, especially when combined with the method of Toepfer. The combination of these two methods renders possible the exact determination of the amount of free hydrochloric acid, the amount of acid-combined chlorine and the amount of neutral combined chlorine, in any given special gastric fluid. By comparison of these elements, it is possible to determine the coefficient of digestive work done upon albumin in the stomach.

In the examination of over 17,000 stomach fluids by these methods, which has been carefully done in the Physiological Laboratory connected with the Battle Creek Sanitarium, it has been found, almost without exception, that the coefficient of proteid

digestion is low in hyperchlorhydria as compared with normal digestion and with hypopepsia. In hypopepsia and normal digestion, for example, the coefficient generally ranges from .85 to 1.25, and sometimes even higher, while in hyperchlorhydria it is not uncommon to find a coefficient as low as .30 .40, and sometimes even much lower. The fact has been noted by other observers who have made careful determinations of the coefficient of digestive work.

In a recent paper by Bellamy (Lancet, September 28, 1901), the position was clearly taken that the objective point of therapeutics in hyperpepsia should be to increase the pepsin formation; and this should be accomplished by a regulation of the dietary rather than by the use of medicaments. Laboratory experiments and actual experience show that this can be accomplished by the administration of dextrin. For scores of years dextrin has been employed with success in the treatment of gastric disorders at Carlsbad, the dextrin being administered in the form of zwieback. For twenty-five years the writer has made use of the same method, in the same way, and for a number of years back he has systematically administered to all his patients suffering from hyperpesia, at the beginning of each meal, a liberal quantity of dextrin in the form of wheat flakes, thoroughly cooked and roasted until slightly browned. By this mode of preparation the starch of the wheat is converted into achroödextrin. It is possible also that there is some other substance associated with the dextrin, the nature of which has not yet been fully determined, to which the stimulation of pepsin formation is really due. This would seem to be the case, from the fact that the purified dextrin known as white dextrin is absolutely inert. We also find in this fact a valuable hint that ought not to be forgotten, and which suggests that the treatment of food stuffs by chemical processes may so change their properties as to render them of little or no value as food, although their composition may remain unchanged. It is

on this ground that the writer has always objected to the substitution of glucose for natural sweet stuff, and this may practically afford the possible explanation for the gastric disturbances set up by cane sugar in such a multitude of cases.

It is not necessary that one should swallow commercial dextrin in order to obtain all the benefits which may be derived from this powerful peptogen. It is essential only that a considerable part of the meal shall consist of cereal substances which have been properly prepared by thorough cooking, and subsequent subjection to a temperature of 280° to 300° for a sufficient length of time to dextrinize the starch. Browned rice and the toasted wheat flakes, well browned zwieback, and granose flakes or granose biscuit, slightly browned, afford just the elements required by cases of this sort. It is best that these food stuffs should be taken dry, as this secures a liberal admixture of saliva, which, acting upon the starch, may convert a considerable portion of it into peptogenic dextrin.

In the treatment of hypopepsia, in which there is a deficient formation of acid, it is necessary only to take care that the food contains a sufficient amount of substances capable of stimulating acid formation. It is not necessary to suppress the dextrincontaining substances, for these can do no possible harm by aiding the stomach in the formation of its pepsin; but the substances which encourage acid secretion must be added. The most powerful substances of this sort appear to be extractives of meat and leguminous seeds. Research will doubtless develop other sources of "succagogues," as Pawlow terms these acid-promoting sub

stances.

These researches afford a rational basis for the management of gastric disorders by a regulation of the dietary rather than by a system of medication, as Bellamy well says: "The simple, and even nourishing nature of the substances which may be employed to further the production either of juice or pepsin, is a great consideration in favor of their use. Nature is, so to speak,

assisted through the agency of her own materials; food is necessary for the maintenance of life, and it should be the aim of the therapist to remedy the cause of disordered digestion through the natural channel offered by alimentation rather than by the more artificial, but in no more scientific resources, of pharmacodynamics."

A practical point which may be further mentioned, is that the administration of dextrin by the rectum stimulates the formation of pepsin as well as when the dextrin is administered by the stomach. It is hence possible to bring into action this powerful peptogenic substance in cases in which there is deficiency of pepsin without introducing into the stomach fermentable substances, the digestion of which might be interfered with by the gastric juice. By the administration of both dextrin and extractives it is found possible to increase gastric activity twenty-five to thirty times.

A NEW CONSTITUENT OF BONE.

GIES, in American Medicine, says that early in the last century (1838) Johannes Müller was the first to observe that when hyaline cartilage is boiled in water a product is formed which closely resembles gelatin, physically and chemically. Müller gave the name "chondrin" to the cartilage jelly formed in this way. Marchand, a few years later, applied the term "chondrigen" to the antecedent substance in the tissue which on boiling was transformed into "chondrin." For many years "chondrin" and "chondrigen" were looked upon as distinct and definite chemic substances, and numerous deductions regarding connective tissue relationships were based upon this assumption.

About a decade after Müller's discovery, Hoppe-Seyler, in a study of their decomposition products, showed that these proteid materials were not as nearly related to gelatin and collagen as had been inferred. Subsequently, Bödecker and others found that

a reducing substance could be separated from "chondrin." Eichwald and Obolensky, about the same time, obtained similar reducing bodies from various mucoids.

This coincidence led Von Mering in 1873, under Hoppe-Seyler's direction, to make a search for mucoid in cartilage. He identified it in aqueous extracts of the tissue by the acetic acid method. Three years later, Morochowetz, under Kühne's direction, made more extended experiments in this connection and demonstrated that "chondrin" is a mixture-containing gelatin, mucoid and inorganic matter. Mörner has lately shown that cartilage contains collagen, albumoid (elastin?), chondromucoid and chondroitin sulphuric acid, in considerable quantity, and that "chondrin" is a mixture of gelatin, chondromucoid, chondroitin sulphuric acid and soluble salts.

We now know that mucoids are normally present, in small quantity at least, not only in cartilage, but all forms of connective tissue, although for a long time this fact was not appreciated. The author has lately. shown the presence of mucoid in bone, thus establishing closer chemic relationship between mature bone and cartilage than had been supposed to exist, and demonstrating, further, that, as far as mucoid content is concerned, osseous tissue is not an exception among connective tissues, as previously it seemed to be.

In referring to Morochowetz's discovery that "chondrin" is a mixture containing mucoid, Drechsel, in 1883, wrote as follows:

"If chondrin is in reality gelatin and mucin the transformation of cartilage into true bone is all the more easily comprehended, for in that case such development would consist essentially in only the elimination of the mucoid constituent." The deposition of inorganic matter in addition is, of course, to be understood.

For years it has been said that cartilage would yield "chondrin," but that true bone would not. The views of Hofmann, expressed in 1875, are representative of those held in this connection until very recently.

He stated that "chondrin may be obtained from bone before ossification, but ossified bone yields only gelatin. Embryonic bones contain no collagen, but do contain chondrigen, which is not transformed into the first-named, but before ossification is displaced by it. Completely calcified bone does not contain even a trace of chondrigen." Until the author's work was begun it had been generally accepted that osseous tissue does not contain glucoproteid. An examination of the statements in recent textbooks on the chemic qualities of bone shows that the pressure of mucoid is either denied or the question ignored.

The later and more prominent experimental results repeatedly given as authority for the statement that mature compact bone does not contain mucoid, have led to inaccurate conclusions. Von Ebner, in 1887, indicated that the decussating fibers of Sharpey are similar to those in fibrous connective tissue in general, and that they are not calcified, but that the calcareous deposit in bone is confined to the interfibrillar areas. These observations led Young* to investigate the question whether the matrix, in which the fibers of the bone structure are embedded, "is completely calcified or not." He concluded that this question could be most readily solved by ascertaining whether mucin, "the most abundant constituent of the uncalcified matrix or ground substance of connective tissue, is present or absent." Working under Halliburton's superintendence, Young failed to extract from bone, with lime-water or dilute baryta-water, any substance that could be precipitated with acetic acid. He concluded, because of this seeming absence of glucoproteid from compact bone, that "in the process of ossification the connective tissue matrix is apparently completely calcified."

Unfortunately this important conclusion was brought about by three very obvious defects of procedure. In the first place, Young employed too much alkaline extractive fluid in proportion to the amount of

*Young: The Journal of Physiology (English), 1892, vol. xiii, p. 803.

bone taken in his experiments, thus making it exceedingly difficult to detect any existent mucoid. Again, the absolute quantities of bone extracted were so small that no positive result could reasonably have been expected.

The chief objection, however, to the method Young employed was the direct application of dilute lime or baryta-water to a dense, compact tissue, thoroughly impregnated with salts which for the most part are insoluble in such medium. It is not difficult to understand how, in the case of the femur, for example, the stone-like structure of the compact portion, composed as it is largely of tribasic earthy phosphates, imposed a serious obstacle to the usual action of limewater on contained mucoid substance, and therefore it is natural to assume that for this reason, if for no other, no glucoproteid was detectable in Young's experiments. Certainly, removal of the salts from bone. is the necessary preliminary to extraction. in dilute alkali, if any hope is to be entertained of finding mucoid in that tissue.

The several difficulties just alluded to have been overcome by very ordinary means, and the author has succeeded in ob- . taining a surprisingly large yield of mucoid from both the femur and the rib of the ox by the following general method:

After the fresh bones had been thoroughly freed of adherent muscle and connective tissue, they were kept in 0.2 to 0.5 per cent. hydrochloric acid for the removal of inorganic matter. In the course of a few hours the dilute acid took out the salts from the surface of the bones just as satisfactorily, although not as rapidly as stronger acid would have removed it. After this treatment the bones were scraped twice daily with a stout, well-sharpened scalpel. The superficial decalcified layer was thus easily removed in long, narrow, thin, elastic shavings, very soft and pliable. The dilute acid was completely renewed after each scraping. The ossein obtained in the first two scrapings was thrown away, for fear it was contaminated with minute particles of superficial connective tissue elements be

longing to the periosteum, which might not have been completely removed in the preliminary treatment. While the shavings accumulated they were kept in dilute alcohol to prevent putrefactive changes. As much as six to seven kilos of moist shavings were used at one time. The shavings were next run through a meat-chopper, and the resultant hash thoroughly washed free of alcohol and acid by decantation in distilled water. Finally the bulky ossein hash was transferred to several large bottles and repeatedly shaken at intervals for about 48 hours, with moderate excess of half-saturated lime-water. On strongly acidifying the filtered extract with 0.2 per cent. hydrochloric acid, a bulky flocculent precipitate rapidly separated. This was purified by the process of washing, reprecipitating, etc., usually employed for final preparation of pure glucoproteids.

This newly-discovered substance, osseomucoid, is practically the same as the mucoid in tendon, cartilage and other connective tissues. It not only responds to the general proteid tests, but appears to have the same solubilities and precipitative reaction as the other connective tissue mucoids, and yields the same large proportion of reducing substance on decomposition with mineral acids. Furthermore, the combustion equivalents of osseo-mucoid, chondromucoid and tendomucoid, as shown in the table below, are practically identical, indicating close chemic relationship of these glucoproteid products.*

The average composition of four purified preparations of osseomucoid is given below, where comparison may also be made with the elementary composition of similar prod

dinary compact bone, like the other forms of connective tissue, contains mucin substance, and also, contrary to Young's deduction, that in the process of ossification, the connective tissue matrix is not completely removed. Further, it makes it easier to understand the accumulation of mucoid in various pathologic formations in osseous tissue which numerous observers, in recent years, have shown may often be considerable in amount.

The influence of disordered metabolism of this mucoid substance on the development of various bone tumors, particularly of the myxomatous type, can only be guessed, at present, but may prove to be more pronounced than the writer now supposes. poses. Our knowledge of mucoid degeneration, not only in bone, but also in other tissues, will doubtless greatly advance as we learn more definitely the chemic phases of glucoproteid synthesis under normal conditions, and as we come to an understanding of the functions in the tissues of the various forms of these peculiar sub

stances.

THE POMELO.

B. B. BOLTON, M.D., in Pacific Health Journal.

THIS is a variety of citrus fruit which has been introduced into the American market during the last few years. The tree, which closely resembles that of the orange, is a native of China and Japan, but is now cultivated in California, Florida, West Indies, Hawaii, and other tropical countries. There are in California about 7,000 trees, 2,500 of which are already. bearing.

The fruit, which is quite smooth and round, and of a pale yellow color, is larger than the largest orange, and filled with a similar pulp, which contains a large amount of juice.

Owing to its habit of bearing in clusters. it has often been called "grape-fruit." This