The possession of a technique which permitted rapid estimations of cardiac output and which, demanding no intelligent cooperation, seemed especially suitable for use on ward patients, has permitted an extensive study on the action of common drugs on the heart and circulation in clinical conditions. This study contains about 450 estimations of cardiac output performed on 85 patients.Coincidentally with these estimations the action of drugs on pulse rate, on blood pressure, on respiratory rate and volume, and on metabolic rate was observed. Orthodiagrams and electrocardiograms were secured also. Therefore, certain parts of our study dealt with effects already well known.The results of such estimations have permitted the calculation of heart work, of peripheral resistance, of arteriovenous oxygen difference, and of the ratio of heart work to heart size, the latter a factor of decisive importance in our conception of cardiac stimulation and depression. Therefore our study demonstrates the effect of drugs on these functions also.Most of the drugs selected are commonly used in cases of cardiac and circulatory disease. We have studied the actions of digitalis, epinephrine, ephedrine, caffeine, theophylline, carbaminoylcholine, sodium nitrite, nitroglycerine, pitressin, quinidine, morphine and strychnine. We have studied the effects of drugs in those clinical conditions in which physicians are accustomed to employ them.But when suitable cases were not available the effects were studied in other conditions. Almost without exception our results support the general conceptions of drug action derived from animal experiments. PROCEDUREAll estimations were performed in the morning. The patients received no food after their evening meal and no water after midnight. They were taken from the ward in bed or in a wheel chair. An electrocardiogram and an orthodiagram were obtained first. Then the subjects lay down for at least 45 minutes. Duplicate estimations of cardiac output and metabolism were then made, together with repeated determinations of pulse rate, blood pressure, respiratory rate and volume.If the study concerned a rapidly acting drug, this was administered soon after the control estimations. The patient was watched until evidence of the drug's action became manifest objectively. Duplicate estimations of cardiac output and metabolism were then made, the purpose being to make these determinations at the height of action. Orthodiagrams and electrocardiograms were secured immediately afterward. Cardiac output was estimated by the method of Starr and Gamble (1), the analyses being performed by the katharometer method of Donal, Gamble and Shaw (2). Metabolism was estimated from samples of expired air drawn from a mixing bottle containing a fan.Respiratory volume was obtained by reading the spirometer at frequent intervals. Respiratory rate was counted repeatedly during the period of observations. It is well known that subjects breathing from a spirometer under 3 mm. H,O negative pressure, and through valves, tend to breathe...

Use of polyoxyethylene preparations in a wide variety of food products has aroused considerable interest in the effects which might follow their ingestion in food. On the basis of an evaluation of 48 published and unpublished reports available to it, the Food Protection Committee ( 4 ) of the National Research Council concluded in 1953 that the data "fail t o demonstrate that polyoxyethylene stearates are safe for use in foods under all patterns of dietary consumption and for all segments of the population. " Other publications have mentioned deleterious effects of polyoxyethylene and sorbitan compounds following oral (13,22,29) and parenteral (3,5,14,15,19,22,23,25,27,28) administration to various experimental animals as well as after in vitro use (1, 10, 12,20,21,23).Recently Krehl, Cowgill, and Whedon (16) reported that polyoxyethylene esters fed to rats and cats for varying periods of time did not have deleterious effects. Graham, Teed, and Grice (7) obtained negative results when they fed polyoxyethylene monostearate to rats in a bread diet for one year. Graham and Brice also reported negative results from feeding polyoxyethylene monostearate in a synthetic diet for 32 weeks (6). The observations reported in the present paper involve the feeding of polyoxyethylene preparationsb for a period of 21 weeks in rats and 39 weeks in hamsters. PROCEDUREFour experiments have been completed to determine the effects of moderate and high levels of several polyoxyethylene compounds in the diet. High levels were used in these experiments in conformity with recommended procedures for evaluation of the safety of chemicals in foods (17, 18). I n the first experiment, weanling male rats (Holtznian Rat Company, Madison, Wisconsin), distributed into 4 groups, were fed for 21 weeks on synthetic diets containing 25% levels of lard; cottonseed oil mono-and diglycerides (CMDG) ' ; polyoxyethylene monostearate (PMS No. 1) d ; or polyoxyethylene sorbitan nionolaurate (PSML)". These diets differed only as to the control or test " D a t a were presented originally in Exhibit 365, Ice Cream Hearings, Docket FDC 34A, 1952. These materials were offered on the open market for use in food products. They were mixtures of many chemical compounds and undoubtedly contained traces of unidentified impuritiex. The heterogeneous composition of polyoxyethylene stearates has been discussed at some length in a report issued by the Food Protection Committee ( 4 ) .A commercial equilibrium mixture of mono., di-, and triglycerides prepared by reacting partially hydrogenated cottonseed oil with glycerine. It will be identified subsequently in this paper by the abbreviaiion CMDC.A partial ester of commercial stearic acid and prefabricated polyethylene glycol, which will be identified subsequently in this paper by the abbreviation PMS No. 1.' A partial ester of commercial lauric acid, sorbitan, and mixed polyoxyethylene diols having a n average chain length corresponding to 20 ethylene oxide units per mol of sorbitan. It will be identified subsequently i ...

EXPERIMENTAL Acute oral toxicity. The niediaii lethal dose studies were performed on male rats (150-280 g.), 011 yamig adult hamsters, and on rabbits (3-4 kg.), all of which had a Presented as Exhibit 366, Ice Cream Hearings, Docket FDC 34A, 1952. " These niaterials were purchased 011 the open market for use i n food products and contained traces of unidentified impurities. They will be designated by chemical rather thaii trade names, with an average figure indicated for the mols of alkylene oxide per mol of sorbitail or of f a t t y acid. The abbreviations that will be used hereafter are given in Table 1.

Representative cottonseed salad oils, corn oils, lards and hydrogenated vegetable shortenings, and portions of the same fats heated at 182 C for 120 hr were fed as 20% of nutritionally adequate diets to weanling albino rats in longevity studies. Differences in the responses of rats fed diets containing the unheated and heated fats were generally small with respect to rates of gain, 12 th week and adult weights, efficiencies of utilization of absorbed energy, incidences of grossly detectable diseases and longevities. There were no indications that the feeding of the heated fats had shortened survival times in comparison with the comparable unheated fat. Animals fed hydrogenated vegetable shortening, heated or unheated, survived the longest. However, gains were slightly slower with the heated cotton‐seed oil diets, and food efficiencies were slightly lower with the heated cottonseed oil and heated lard diets because of decreased digestibilities of these fats. The usual disabilities of old age such as nephritis, respiratory disease and periarteritis were present in all groups. The incidence of mammary tumors was high but did not differ significantly with the kind of fat, heaated or unheated. Tumor incidence other than mammary was similar in both sexes and there was no significant difference between fresh and heated fats. Absence of adverse effects attributable to the heated fats during the life span of the rats in further evidence of the safety of these fats of the quality customarily consumed by the human population.

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