Harold W. Brown

Alteration of endogenous catecholamine metabolism by ethanol ingestion.

Summary Ingestion of moderate amounts of ethanol by normal human subjects results in a striking decrease in excretion of 3-methoxy-4-hydroxymandelic acid and a compensatory increase in excretion of 3-methoxy-4-hydroxyphenylglycol. These findings are supported by previous studies using C14-norepinephrine and indicate that ethanol ingestion diverts the intermediate metabolism of both epinephrine and norepinephrine from the normal oxidative route to a reductive pathway.

An Effective Ascaricide-Hexylresorcinol.

Ascariasis is a condition which has been recognized since the earliest medical times, and although it may cause little apparent disturbance the parasites are always a potential source of danger from migration into the various body cavities, from mechanical obstruction of ducts, the air passages, or the intestines, and from chemical intoxication. Between the latitudes of 35° North and 30° South there is a belt of ascariasis around the entire world. In the rural population of certain states of this country which lie in this belt, there is an incidence in certain areas as high as 48%, 1 while in other countries, such as China, as many as 90% of the population of certain regions have been found to be infested with these parasites. A great many substances and concoctions have been used for the removal of these worms, but they have all proven to be either inactive or dangerous. The two in most common use at present are Santonin and Oil of Chenopodium (or its active principle, Ascaridol). Both of these substances have been given to many thousands of patients without intoxication. On the other hand many sudden unexplained deaths have followed their use, which makes it impossible to predict what will be the outcome of their administration. Carbon tetrachloride and tetrachlorethylene, which are both very efficient against hookworm, are relatively ineffective against ascaris and may cause dangerous migration of these parasites. 2 We have, therefore, no safe or effective means of removing ascaris. On this account a search for a non-toxic ascaricide was begun several years ago in this laboratory, and a great number of experiments have been carried out on the physiology and pharmacology of this parasite.

Hexylresorcinol in the Treatment of Hookworm Disease.

Hexylresorcinol was recently found by us to be an effective ascaricide, killing Ascaris suum quickly in vitro, removing in single therapeutic doses practically 100% of the ascarids from dogs and 90% or more from man. 1 , 2 , 3 Leonard has found this substance very non-toxic in his clinical work on urinary antisepsis, 4 and we have treated 1500 human cases for ascariasis without symptoms of any consequence. 5 Our laboratory experiments showed hexylresorcinol to be also effective against hookworm in dogs. 2 Through the kindness of Dr. W. W. Cort of the Johns Hopkins School of Hygiene, and Dr. A. T. MacCormack, Commissioner of Health for the State of Kentucky, arrangements were made by which we could treat and re-examine cases of ascariasis studied in the survey being carried out by Dr. Cort on the distribution and incidence of ascariasis in the United States. A field laboratory was set up under the directorship of Dr. G. F. Otto of Dr. Corts department, in Jackson, Kentucky, with a technical staff for making egg counts by the Stoll Method. 6 Dr. H. W. Brown of this department was in charge of all treatments, recollections, and recounts. Of the 6,000 cases examined by Dr. Corts staff, 1,350 cases of ascariasis were treated by Dr. Brown and Dr. B. H. Robbins; 1,000 recollections were made 2 weeks after treatment, and egg counted. Among these, 530 cases harboring hookworms were found and treated. These hookworm treatments were incidental to the more complete studies of hexylresorcinol in ascariasis and are necessarily incomplete. The cases were treated with various amounts of the drug at different times in widely separated communities and under all manner of conditions. Those here reported are a summary of the effects of therapeutic doses of hexylresorcinol given as crystals in hard gelatin capsules and followed by water in some instances and mineral oil in others.

Oral Toxicity of Ortho-n-alkylphenols to White Rats.

Conclusions 1. The oral toxicity of ortho-n-alkylphenols to white rats decreases with the increase in length of the alkyl radical. 2. This decrease in toxicity with increase in length of the alkyl radical corresponds to our toxicity findings in series of 6-alkyl-meta-cresols and 4-n-alkylresorcinols. 3. Ortho-n-alkylphenols are less toxic than n-alkylresorcinols with the corresponding length of alkyl chains but show little difference in toxicity from the 6-alkyl-meta-cresols with the same number of substituted carbon atoms.

The Anthelminthic Properties of Certain Alkyl Phenols.

Several years ago a search was begun in this laboratory for a safe and effective human ascaricide. Among the many substances tested in vitro, hexylresorcinol was found to have as great activity as any and certain advantages which made its further study seem advisable (1). The results in human ascariasis have been encouraging as shown by the following reports of its use. Quite incidentally the effect of hexylresorcinol against hookworm (2), trichuris (3), enterobius (4), etc., was studied but our chief object has been to find an effective ascaricide. As far as we can tell from laboratory experiments (5) and the reports of field treatments, a very effective and safe drug for uncomplicated hookworm disease is known in tetrachlorethylene which was first introduced into medicine in 1925 by Maurice C. Hall (6). As tetrachlorethylene is a poor ascaricide and may possibly stimulate ascaris to migrate, other treatment may be advantageous in mixed infestations, but, for uncomplicated hookworm, tetrachlorethylene is, as far as we know, the best drug which we have.