results or only slight and temporary improvement, so I felt that treatments should be given at more frequent intervals. Then I tried a method of giving the weakest dilution every day, the next strongest every other day, and so on, in other words, as the dose of pollen extract was increased, I also lengthened the interval between treatments. As a working basis, I adopted the following: 1:20,000 or 1:10,000 dilution doses every day, 1:5000 dilution doses every other day, 1:1000 dilution doses every third day, and 1:500 dilution doses every fourth day. This seemed to me to be quite an improvement over Walker's method of giving injections only every five to seven days, in that some cases were rendered entirely free of all hay-fever symptoms, but in some few cases, the hay-fever was apparently aggravated by over-treatment, which I conIcluded was due to the fact that my schedule of treatment was too arbitrarily fixed for the individual case. As a result of this, I decided to regulate the interval between treatments, according to the amount of relief obtained from any individual treatment. Each patient treated co-seasonally, was instructed at every treatment, that if he received no benefit from that particular treatment, to report the next day, at which time I gave him a larger treatment with the same instructions. If relief followed any individual treatment, he was instructed not to report for further treatment, until he began to slip back, or in other words, until the effect of the treatment began to wear off. Treatments were thus given from a day to a week apart.

Skin tests were of course used in every case, to select the proper pollen or pollens for treatment, and also to determine the proper dilution of the specific pollen extract with which to begin treatment. A safe rule for selecting the proper dilution with which to begin treatment, is to use the strongest dilution which fails to give any skin reaction whatsoever in the particular case.

With these general considerations before you, I should like to present a few cases illustrating this method of treatment, giving only such information as has a direct bearing on the subject under discussion. I have purposely chosen cases representative of more than one hay-fever season, in that it may not be said, that the results were due to some seasonal variation.

Case 1. Mr. W. H. C., aged forty-seven years. Referred by Drs. Hyde and Greene. Had autumnal hay-fever ever since he was a child. Has asthma at night during hayfever season. Perfectly well all the rest of the year. Deviated septum, operated on in 1892 or 1893. In summer of 1917 he had some tests, and inoculations with a stock combined pollen extract were started in July, which he thinks helped him a little.

Patient was first seen August 29, 1922, during attack of hay-fever. He was found sensitive to ragweed, and was given three treatments (ragweed short) as follows: August 31, 1922. September 7, 1922. September 15, 1922. Under this treatment he became practically free of all symptoms of hay-fever, and remained so in spite of a long train trip before the middle of September.

1:10,000 (0.1 cc.) 1:10,000 (0.2 cc.) 1:5000 (0.1 cc.)

Case 2. Mrs. F. W. C., aged twenty-one years. Referred by Dr. Wood. Seen September 26, 1922, during her first attack of fall hay-fever, which had started about August 20, 1922. She sneezed all the time.

Eyes itched dreadfully, were quite bloodshot, and tears seemed to come continuously. Was unable to breathe through nose when lying down at night, but no asthma. She woke up three or four times every night, in fact had not had a whole night's sleep since her trouble started. Usually woke up very early in morning sneezing. She went to Great Falls, Virginia, September 23, 1922, following which she sneezed all night, and her hay-fever was much worse the next day. Cannot go any place where there is vegetation, without aggravating her trouble.

On skin test she reacted to short ragweed down to a 1:1000 dilution, and giant ragweed down to a 1:5000 dilution. On September 27, 1922, she was given the following treatment:

Ragweed short, 1:5000 (0.1 cc.)

Ragweed giant, 1:10,000 (0.1 cc.) Another similar treatment was given on October 2, after which she had no further trouble. Although this was rather late in the season, other ragweed sensitive cases, were still having definite symptoms.

She had no more hay-fever until the following ragweed season, and I did not see her again until September 11, 1923, at which time I gave her ragweed short and giant mixed 1:10,000 (0.1 cc.) of each. Another treatment was given September 17, 1923, as follows: Ragweed short and giant mixed extract 1:10,000 (0.2 cc.), after which she had no more trouble. I am now giving her pre-seasonal treatment with short and giant ragweed.

Case 3. Mr. H. J. P., aged twenty-six years. Hay-fever, started in 1913 or 1914. Has been severe ever since 1917, and he has had it every season, no matter where he was, Georgia, New York City, Virginia, etc. Starts about the middle of August and lasts until real cold weather. Entirely free all the rest of the year. Intense itching of eyes and ears, and way back in the roof of his mouth, but only during hay-fever season. Sunlight and vegetation seem to aggravate his hay-fever. Lived in the country, and while he was in the city his hay-fever was not so violent. Hay-fever worse on dry, dusty days. On damp, rainy days, is at times almost entirely relieved.

Worse outdoors than in the house. I first saw him September 4, 1923.

On skin test, taking a 1-inch urticarial wheal as a + and a 4-inch wheal as a ++ he gave a ++ reaction to short ragweed, a ++reaction to giant ragweed, and a ++++++ reaction to sunflower. On the basis of these reactions, I decided to treat him with a mixed pollen extract, containing short ragweed, giant ragweed and sunflower. To show how sensitive he was to these three pollens, I will give his reactions to various dilutions of this mixed extract. 1:100 +++, 1:500+, 1:1000+, 1:5000 slight reaction, and 1:10,000 gave a doubtful

reaction.

On September 5, 1923, he was given ragweed short, giant and sunflower mixed 1:20,000 (0.1 cc.).

On September 8, 1923, ragweed short, giant and sunflower, 1:10,000 (0.1 cc.).

About twelve hours after his second treatment, he had practically complete relief from his hay-fever, and he remained free during the rest of the season. He stated that the effect of the treatment was almost like a miracle in his case.

As sunflowers are insect pollinated, and therefore the pollen is not present in the air, I could have probably just as well eliminated it from his treatment. I am now giving him pre-seasonal treatment with short and giant ragweed.

Case 6. Miss E. D., aged twenty-eight years. Hay-fever and asthma. Started early in fall of 1917 and lasted until frost. Had it every year since, starting in August and lasting until October. Free all rest of year. After she has hay-fever about three weeks, her nose stops up entirely, then asthma sets in. Her eyes itch, get red, and water just pours out of them, and a sort of crust forms over them. First seen September 10, 1923.

Sensitive to short and giant ragweed. Treatment with short and giant ragweed mixed as follows: September 12, 1923. September 19, 1923. September 26, 1923.

October 3, 1923.

1:20,000 (0.1 cc.) 1:10,000 (0.1 cc.) 1:10,000 (0.2 cc.) 1:10,000 (0.3 cc.)

She was practically free of hay-fever after the first treatment.

DISCUSSION

In discussing co-seasonal treatment Walker (4) has said:

Frequently patients present themselves for treatment during their hay-fever attack, and although pollen treatment at this time does not seem to be very logical, on the basis of anaphylaxis, the patient often will insist on taking the chance. Pollen treat

ment during the season does not seem logical, because the patient is being injected with the pollen which is causing symptoms, at the same time that he is being exposed to the pollen present in the air which he is inhaling. The danger resulting from large doses of the injected pollen is obvious because of an overdose, due to the combination of the injected pollen and the inhaled pollen. Therefore, in order that duringthe-season treatment should be beneficial, the patient must be injected with minute amounts of the pollen extract, in order to diminish artificially a few of the patient's antibodies, thus leaving a smaller number of antibodies in the patient for combination with the pollen antigen, that is inhaled. If too much pollen extract (antigen) is injected, the patient should have symptoms due to over-treatment alone, or he should be made worse, due to the injection of pollen extract (antigen) superimposed on the inhalation of pollen (antigen). It is evident, that on the basis of anaphylaxis, during-the-season treatment is hazardous, and although the skin test is the best guide as to the proper treatment, there is no way of controlling the amount of pollen that the patient may inhale.

In answer to the objection raised by Walker regarding the injection of pollen at the same time that the patient is inhaling it from the air, I might say that I have frequently found it necessary to treat so-called perennial hay-fever cases with some protein extract while they were inhaling the same substance. For example, in perennial hay-fever cases sensitive to their own house dust, it is practically always necessary to treat them with an extract of the house dust while they are breathing the same substance. Also, cases sensitive to the animal epidermals, orris root, wheat flour, etc., are frequently either unable or unwilling, due to occupation or other reasons, to avoid contact with the particular offending substance

while they are being treated. I have never observed, however, that treating a patient during exposure to the offending substance, has prevented desensitization. I am willing to admit that treatment under these circumstances is more difficult, as greater care must be exercised in selecting the initial and subsequent doses. Furthermore, in case there is an aggravation of symptoms, it is desirable to determine whether it is due to treatment or not. In regard to this point, I would say that where an aggravation of symptoms occurs that is due to treatment, it usually follows shortly after the treatment, and the more severe the reaction, the sooner it follows the treatment. Also, constitutional reactions from treatment are almost invariably accompanied by a marked local reaction, namely, an inflamed, swollen arm. In addition to this, constitutional reactions from treatment are frequently manifested by symptoms other than those of hayfever, such as generalized urticaria. (hives), or asthma. By exercising careful judgment in the selection of proper dosage, constitutional reactions

(1) SCHEPPEGRELL, W.: Hayfever

very rarely occur, and when they do, are promptly controlled by the subcutaneous injection of adrenalin chloride (1:1000) 0.5 to 1 cc.

Vaughan (8) in one of the very few articles commending the co-seasonal treatment of hay-fever, stated that

During the pollen season, the nasal mucosa is bearing the brunt of the allergic reaction. The administration of pollen elsewhere, as through the skin, would theoretically distribute the reaction throughout the other tissues, thereby relieving to some extent, the intensity of the local reaction.

CONCLUSION

Although pre-seasonal treatment, started far enough in advance of season to get the patient as completely desensitized as possible just before pollination of the particular offending plant or plants (ragweed), is undoubtedly the ideal method of treating fall hay-fever, co-seasonal treatment is well worthy of trial in those cases in which pre-seasonal treatment has been incomplete, or in which there has been no pre-seasonal treatment.

and

Asthma. Lea & Febiger, 1922. (2) HOLLOPETER, W. C.: Hay-fever, Its Prevention and Cure. Ed. 4. Funk & Wagnalls Company, 1922. (3) BERNTON, H. S.: Treatment of seasonal hay-fever, and some possible causes of failure. Jour. Amer. Med. Assoc., May 5, 1923, lxxx, 1301-1308.

(4) WALKER, I. C.: Frequent causes and the treatment of seasonal hay-fever. Arch. Int. Med., July, 1921, xxviii, 71-118.

(5) WALKER, I. C.: Hay-fever, the late summer and fall type. Hygeia, August 1, 1923, i, 291–297.

(6) MILLER, C. M.: Nasal secretion filtrate injected intramuscularly for hayfever. Abst. Jour. Amer. Med. Assoc., June 17, 1922, lxxviii, 1926– 1927.

(7) BROWN, G. T.: Some results of protein sensitization work in bronchial asthma, hay-fever and allied conditions. Report of Cases. Virginia. Med. Month., September, 1923, 1, 379-384.

(8) VAUGHAN, W. T.: Specific treatment of hay-fever during the attack. Jour. Amer. Med. Assoc., January 27, 1923, Ixxx, 245-247.