Paper - The Aschheim-Zondek hormone test for pregnancy

Kaplan HE. The Aschheim-Zondek hormone test for pregnancy. (1929) Cal West Med. 31(6): 412-413. PMID18741243

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as tumor cells, bunches of bacteria, fat globules, and air bubbles.

Emboli usually start from a vein, such as thrombosed varicose veins, inflamed pelvic veins; also from inflamed veins about the appendix, gall-bladder area, stomach and duodenal ulcers and, lastly, the heart.

We have two types of thrombi from which an embolus may float: (1) Aseptic, as noninflammatory vegetations from the aortic or mitral valves of the heart. (2) Septic emboli, by far the most common, come from inflamed veins, areas of acute endocarditis. Such an embolus may give rise to an inflammation of the veins and artery in the same location, and from this a metastatic abscess may form if the infection pass through the walls of the vessels. A part of the vessel wall may weaken and form a small aneurysm and later the aneurysm may rupture and, as Boyd said, “probably this is the cause of cerebral hemorrhage in young people.”

The amount of tissue affected may be small or extensive, even to the loss of a part, as a limb. The obstruction may be slow or rapid. When rapid the tissues affected die quickly.

To prevent. an embolus is beyond us, but many men in the profession are doing their best to prevent it.

Doctor Bonn has quoted Kennedy, Coffey, and Walters as to their respective methods to prevent thrombus formation, thereby eliminating to a certain degree the cases of embolism. We all believe that it -is important to listen to the advice of all these men.

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PHILIP H. PIERSON, M. D. (490 Post Street, San Francisco).—This paper discusses postoperative pulmonary embolism in a somewhat different manner than most papers on this subject. We are all aware, as stated, that small pulmonary emboli are of frequent occurrence after operation and, of course, generally of very little significance. Sterile emboli rarely cause any symptoms when lodging in a healthy field (one where there is no infection and where the circulation is normally maintained). But these sterile emboli often prepare the field for subsequent attack by either sterile or infected emboli which cause trouble. The recent work of Holman is to be mentioned along this line, showing the difference in the effect in the pulmonary field when an embolus travels into the bronchial artery from that which occurs when it travels in the pulmonary artery. As the bronchial artery nourishes the lung tissue more than the pulmonary artery, occlusion of branches of the bronchial artery often leads to more damage than in the pulmonary artery. The appearance‘ of symptoms is not coincident with the mobilization of a thrombus, for very often when the embolus does not affect the peripheral part of the lung, involving the pleura, no pain is felt for several days. Infection developing in such an area may not manifest itself for from five to nine days. Doctor Bonn has mentioned the question of passive and active motion. It is true that gentle skin massage is of great value in promoting healthy circulation, but deep massage and more energetic exercise, I feel should be avoided for at least two weeks following operation in order that the thrombi may become well organized, thereby diminishing the danger of embolism. Of utmost importance is maintenance of healthy circulation in the lungs as a preventive of trouble resulting from small emboli. Frequent change of position, deep breathing——where possible—-will aid this to a very considerable degree. The preparation of the patient before operation, clearing up any pulmonary infection and any disease in the mouth is most important. Some abscesses are favored by aspirated material from the mouth and, during the first few days following operation, the patient is quite unable to take the care that is necessary of his teeth, and from this source there is no question that some bacteria are planted in the lugéigs.

DOCTOR BONN (Closing).—Since this paper was completed, the article of Miller and Roepke on “Thrombosis and Embolism” (Zeit. f. Chir., 1928, Vol. IV.,

CALIFORNIA AND WESTERN MEDICINE

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p. 224), has been abstracted by the International Abstract of Surgery of November 1928. This article discusses the pathologic-anatomical aspects of thrombosis and embolism in an admirable manner and is perhaps the most complete exposition of the subject from this standpoint. Dietrich, Ritter, Freund, Ruff, Butzengeiger, Stegeman, Colmen, Naegli, and Killian also discuss this article, and it is interesting to note that there apparently exists abroad as much divergenlfe of opinion on the various angles of this subject as ere.

THE ASCHHEIM-ZONDEK HORMONE TEST FOR PREGNANCY*

By HARRY E. KAPLAN, M. D.

Stockton

• Read before the Obstetrics and Gynecology Section of the California Medical Association at the Fifty-Eighth

Annual Session, May 6-9, 1929. December, 1929

DISCUSSION by John C. Irwin, M. D., Lo: Angeles;

Ludwig A. Emge, M. D., San Francisco; Gertrude Moore, M. D., Oakland.

MY purpose in presenting this article is to report briefly my experiences with the Aschheim-Zondek test for pregnancy which I had the opportunity of observing last winter in the laboratories of the Jewish Hospital of Brooklyn, New York.

NEED OF A DEPENDABLE TEST

There has long been a want for a desirable and dependable laboratory test for pregnancy. Erdheim and Stumme} pointed out that during pregnancy marked changes in the histologic structure of the anterior lobe of the pituitary gland take place. Smith and Engle 2 and Evans and Long 3. demonstrated that the injection of anterior lobe of the pituitary gland into mice and rats caused marked enlargement of the ovaries. Aschheim and Zondek,‘ confirmed these observations and discovered that during pregnancy there was a striking overproduction of the hormone of anterior lobe of the pituitary gland, leading to its excretion in the urine. They also found that the subcutaneous injection of urine of pregnant women into immature female mice was followed by striking alterations in the ovaries, manifested by swelling, congestion, hemorrhage, and the premature maturation of the ovarian follicles. These changes were easily visible to the naked eye. Louria and Rosenzweig 5 carried out this test in one hundred and thirty-two cases. Eighty-seven specimens came from women in all stages of pregnancy and showed a positive reaction in 98 per cent. For controls they used the urine of nonpregnant women, among which were the urines from patients with fibroid uterus, ovarian cysts, functional amenorrheas, as well as normal women in the premenstrual and postmenstrual epochs and in the menopause. Specimens of urine from males were also injected for controls. These showed a negative reaction in 91 per cent.

THE ASCHHEIM-ZONDEK TEST

The Aschheim-Zondek test is performed on female white albino mice, ranging in age from four to six weeks, their weight averaging about

fifteen grams. Three-tenths of a cubic centimeter of urine is injected subcutaneously three times a day for three days. The injections should be at least three hours apart, although they can be separated by more time. It is best to use a rustless needle for the injections. The mice are autopsied on the third day following the last injection or the sixth day after the first injection.

The morning specimen of urine is preferable, although the casual can be used. It is very important not to let the urine stand around and it should be used the same day. It is also very important to keep the urine on ice. A clean bottle should be used for collecting the urine.

The autopsies reveal marked changes in the immature ovaries, such as swelling, congestion, hemorrhage and maturation of the follicles. There is also an associated enlargement and engorgement of the uterus and tubes, but in accordance with the views of Aschheim and Zondek this was interpreted as being secondary to increased ovarian activity. The ovaries in immature mice are small pale bodies. On autopsy, following the injection of the urine of pregnant women, the ovaries of the mice become enlarged to three times the normal size and have a pinkish red appearance. The hemorrhagic areas are visible to the naked eye and stand out prominently on the surface of the ovary. The premature ripening folli V cles are easily seen as small yellow spots.

The earliest case of pregnancy examined was in a woman whose menstrual period was seven days overdue. There were several other women in the first three weeks of gestation, all of whom showed a positive test. The importance in this type of case is obvious in that a diagnosis of pregnancy is possible before physical examination is positive, thereby differentiating the pregnant uterus from the slightly enlarged nonpregnant cu erus.

611 Medico-Dental Building. REFERENCES

1. Erdheim, J., and Stumme, E.: Beitr. z. path. Anat. u. z. allg. Path., 46:l32, 1909.

2. Smith, P. E., d E 1, E. T.: A . ,40:l59, November 1337. nge m. J Anat.’

S3,. M., and Long, J. A.: Proc. Nat. Acad.

4. Aschheim, S., and Zondek, B.: Klin. Wchnschr., 7:30, July 1928.

5. Lour°a, H. W., (1 R ' , M.: , A, , 91:25, Dedember 22,aln928. Osenzwelg J M. A’

DISCUSSION

JOHN C. IRWIN, M. D. (1709 West Eighth Street, Los Ange1es).—I have had no personal experience with the Aschheim-Zondek test of pregnancy, but in July of 1928 had the opportunity of meeting doctors Aschheim and Zondek and watching their work at the Charité Frauenklinik in Berlin, wh-ere the test was perfected. At this clinic I saw Professor Wagner operate upon a case under a diagnosis of left broad ligament fibroid and prove the preoperative diagnosis. This diagnosis had been made because of a negative test for pregnancy in the face of a typical textbook history_ of extra-uterine pregnancy. This case shows the reliance placed in the test at that clinic. Similar results were being found at the clinics in Vienna, where all who had undertaken the test were enthusiastic about it.

In Berlin I was given the following figures by Doctor Aschheim:

The test was positive for pregnancy four times in two hundred and fifty—eight nonpregnant cases. In thirty—two cases of five to six weeks’ pregnancy thirty were positive, and two were negative; in thirty-six cases of seven to eight weeks’ pregnancy thirty-six were positive, and none were negative; in one hundred and three cases of three to ten months’ preg nancy one hundred and one were positive, and two

were negative; in twenty-six cases of unknown duration of pregnancy twenty-six were positive, and none were negative; or four negative reactions in one hundred and ninety-seven cases of pregnancy which equals two per cent errors.

This percentage of ‘error is so small as compared with the Abderhalden and other serum reactions for pregnancy that it seems we can at last discard the older methods. The reliability of the test and the ease with which it can be done makes it possible for every hospital or commercial laboratory to furnish us a quite accurate diagnosis of early pregnancy in the puzzling case. The technique described by Doctor Kaplan is the _same as that used by Aschheim and is much more easily executed than the Abderhalden or any other serum test with which I am familiar. The only diflicult part of it is having female white mice at three to four weeks of age just at the time when the test is to be made, since immature mice must be

‘used. The observations can be made with or without

the aid of a microscope, which is time-saving as a laboratory procedure.

I am glad Doctor Kaplan has brought this test to our attention, and I hope that at least one laboratory in each California city will undertake this test for the profession, as it would no doubt help us in many cases where there is a question of early pregnancy.

LUDWIG A. EMGE, M. D. (2000 Van Ness Avenue, San Francisco).—As far as I can learn from the literature the Aschheim-Zondek test for pregnancy offers the highest percentage of correct diagnoses of any tests so far introduced for the same purpose.

The real value of this test centers in the aid it offers in the diagnosis of pregnancies obscured by tumors and in the diagnosis of extra-uterine gestation. Since the test has proven itself dependable in these groups, its value will be inestimable. The test in itself is simple, and were it not for the constant necessity of having immature mice on hand, could be handled by any good laboratory. The mouse problem complicates matters considerably and confines the test to institutions whose large breeding pens furnish a constant supply of very young mice. In our laboratory at the Stanford women's clinic, Doctor Fluhmann is working at present on a serum modification of this test. His observations are very promising.

Doctor Kaplan’s concise report is very gratifying and creditable for bringing this test to the attention of the profession at large.

GERTRUDE MOORE, M. D. (2404 Broadway, Oakland). Doctor Kaplan’s paper is indeed timely in bringing to the attention of the medical profession a test of such‘ practical value. Our experience with it for the past year has led us to conclude that it is simple in performance, easy of interpretation, and reasonably reliable. Its accuracy in the hands of most workers compares favorably with that of other laboratory procedures. The statement has been made that the test is impractical because the average pathologist cannot have the necessary immature female mice always at hand, but this difficulty has been met in our laboratory by purchasing these animals from commercial producers at the time that the test is ordered. We have found this plan very satisfactory and urge its trial by those ‘who have looked upon this as an insurmountable obstacle, feeling sure that they will conclude, as we have, that it is the only test ever proposed for the diagnosis of pregnancy which is worthy of serious consideration.