Daniel J. Healy

The toxic character of the colostrum in parturient paresis

Parturient paresis is preëminently a disease of plethoric heavy milking breeds of cows, and of those individuals which give the greatest yield of milk. Among the prime and immediate causes of the disease are parturition, a permanent or transient plethoric condition of the blood vessels, with corresponding increase of pressure on the nerve centers of the brain. The phenomenal trophic and secreting activity of the udder of the heavy milker and intense physiological activity of the mammary glands resulting in the sudden rise and absorption into the circulation of leucomaines or toxic alkaloids of the cells of the mammæ. These according to Law 1 are the principal causes operating to bring on an attack of this disease. In the present state of our knowledge it is of little moment whether we call the substances, other than milk, resulting from the sudden disintegrative changes in the udder at or about the time of parturition, leucomaines, alkaloids, toxins, or what not. It seems reasonably certain, however, that there is no gland of the size and physiological activity of the udder of a heavy milking cow, but what must contribute very largely and sometimes malignantly to the internal secretions of the animal. The question, therefore, immediately before us in the study of parturient paresis and of eclampsia in the woman is to determine experimentally whether the udder and the breast, respectively, do under these acutely toxic conditions actually secrete poisonous substances, which if not quickly eliminated or prevented from entering the circulation might be held responsible for these diseases. It therefore occurred to one of us, Kastle, 2 to test the conduct of the first fresh colostrum of the cow obtained during an attack of parturient paresis, upon the lower aninials.

A Filterable Organism Isolated from the Tissues of Cholera Hogs

Suitable mesenteric glands were selected from virus hogs, the glands carefully dissected out of mesentery, covered with 10 times their weight of absolute alcohol, and placed at 37 C. over night. The alcohol was then decanted off, the glands thoroughly ground with sterile sand, and the alcohol again added to the ground glands. The preparation was then placed at 37 C. for 8 days and thoroughly shaken each day. At the end of this period the preparation was filtered through an ordinary, white, folded filter paper. The filtrate, which measured 670 c.c, was evaporated by the aid of an electric fan to a somewhat pasty, deeply yellow mass. This mass was partly dissolved in 225 c.c. of ether and set aside to sediment. The ether was decanted from the sediment and allowed to evaporate to a volume of 15 c.c. To this 15 c.c. were added 75 c.c. (5 times its volume) of acetone. A heavy, flocculent precipitate immediately formed, which was allowed to settle, whereupon the supernatant liquid was decanted. Twenty-five cubic centimeters of methylic alcohol were added to the precipitate. The methylic alcohol dissolved a portion of the precipitate, leaving, however, a deeply yellow, sticky mass undissolved. After sedimentation the methylic alcohol, decanted and diluted 1:10 with normal salt solution (1.5 c.c), was used as antigen in amounts varying from 0.01 c.c. to 0.03 c.c. with, in each case, 0.05 c.c. immune serum, 0.045 c.c. complement, 0.1 c.c. hemolysin, and 0.5 c.c. red blood corpuscles. The antigen, immune serum, and complement were mixed and placed at 37 C. for 1 hour, whereupon the hemolysin and corpuscles were added and the whole placed at 37 C. for 2 hours. Complete hemolysis followed in every case. The test for complement absorption was negative. This test was repeated with 10 times the dose of antigen used in the first test, and the result was again negative.

Calcium Salts and the Onset of Labor

In a recent communication1 we have shown that the colostrum of the normal cow, as well as that of a cow ill with parturient paresis, contains a substance or substances capable of bringing about abortion in pregnant guinea-pigs. It was also shown that the substance or substances in the fresh, normal colostrum which excite the pregnant guinea-pig to premature labor withstand heating to boiling for a short time. We reached the conclusion, therefore, that in this respect the exciting substance of the colostrum resembles the hormones, and the further conclusion would seem to be justified from the experimental evidence obtained in our studies that the onset of labor in the pregnant female is brought about by the internal secretions of the mammary gland. For reasons which we hope to discuss more fully in a subsequent communication, it occurred to us that perhaps calcium salts might prove to be an important factor in the onset of labor. In this connection it is of interest to observe that W. Blair Bell and Paintland Hick,2 in their admirable studies on calcium metabolism and the periodic variation of the calcium content of the blood during the menstrual period in woman, foresaw a causal connection between the fall of calcium in the systemic blood and its corresponding increase in the menstrual discharge, and the onset of labor in the pregnant female. They proved conclusively that there is an excretion of calcium during the menstrual period which is coincident with the fall of calcium in the blood. They have also shown that calcium salts exert a definite influence upon the uterine contractions, with the slight but definite rise of blood pressure. According to these authors a slow, forcible, and ryhthmical contraction of the uterus is produced by the action of calcium salts similar in all respects to that seen in labor; and while they were

The internal secretion of the mammæ as a factor in the onset of labor

The importance of the internal secretions has come to be well recognized in modern physiology and medicine. Among other interesting observations in this field may be mentioned the fact that Miss Lane-Claypon and Starling (Proc. Roy. Soc., 1906, B. 505) have shown that the stimulus to the hypertrophy and lacteal activity of the mammary glands, in pregnant animals, comes not from the ovaries, or the placenta or the uterus, but from the fetus itself. In connection with our studies on the toxic nature of the colostrum of the cow, ill with parturient paresis, we have succeeded in showing that the colostrum both of the normal cow and that of the cow ill with parturient paresis contain a substance, or substances, which have the power to bring on abortion in pregnant guinea pigs; and that neither normal salt solution (0.85 per cent. NaCl) nor the fresh milk of a healthy dairy herd have the power to bring on premature labor. It has also been shown that boiling for a short time does not destroy the power of the normal colostrum of the cow to accomplish premature labor in pregnant guinea pigs. In this abstract of our paper on this subject we have only space for the details of one experiment, which are as follows: Experiment 15.—A healthy guinea pig in the 5th to the 7th week of pregnancy received by intraperitoneal injection 10 C.C. of sterile, normal salt solution (0.85 per cent. NaCl). The injection caused no discomfort and at the end of five days she had not aborted. She then received by intraperitoneal injection 10 C.C. of fresh milk, from a healthy dairy herd. This was heated to 38° C. before the injection.

Parturient paresis and eclampsia. Similarities between these two diseases

In June, 1907, the attention of one of us (Healy) was called by Dr. M. A. Scovell, Director of the Kentucky Agricultural Experiment Station, to parturient paresis in the dairy cow. Dr. Scovells intention was to have, if possible, the etiology cleared up. It proved impossible to take up the problem until one year ago, and as our studies progressed, the similarity between parturient paresis and eclampsia became more and more evident. They are both intoxications which occur suddenly just before, during or immediately after labor. They are characterized by the same clinical features, namely, suddenness of onset, loss of consciousness, coma and similar febrile conditions. In both, the urinalyses are the most important clinical features, and the urinalyses in these two conditions are similar, namely, a disturbance of the nitrogen distribution among the compounds containing nitrogen, an increase of the ammonia excreted, the presence of albumen, and microscopically the presence of hyaline, granular and epithelial casts and blood cells. The finer pathological changes occurring in parturient paresis have not been established, and as none of our cases died, we have not had the opportunity of studying these changes. However, wehave had ample opportunity to study the finer pathological changes in three guinea pigs which died in five, six and seven days under the influence of the toxin of parturient paresis. We have also observed these changes in another guinea pig, which received a smaller dose of the toxin, the dose not being sufficient to cause death in ten days and therefore he was chloroformed. The pathological findings in these guinea pigs correspond in every way to the characteristic lesions of eclampsia, namely, there was hemorrhagic necrosis of the liver, acute parenchymatous nephritis with interstitial hemorrhages, degeneration of the cells of the adrenal cortex, with interstitial hemorrhages, and destruction of the medullary portion.