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Neither immunologic nor genetic concepts of carcinogenesis have yet been decisively confirmed, and epigenetic theories, as formulated so far, are either non-predictive or insufficiently consistent with morphologic and experimental evidence. Computing data, concerned with carcinogenic mechanisms and neoplastic changes at the level of the endoplasmic reticulum, may lead to a new coherent understanding of tumor pathogenesis. Carcinogenic agents initiate biophysical perturbations, chemical alterations and conformational transitions in the membrane lattice of the endoplasmic reticulum. Foremost among the resulting neoplastic changes is an increased, irreversible separation of polyribosomes from membranes of the ergastoplasm. The carcinogenic process, apparently, deletes a protein required for polysome attachment. Since microsomal cytochromes can be synthesized by membrane-bound polysomes only, the translation of genetic information for their biosynthesis is irreversibly restricted. A similar, self-perpetuating deficiency may be postulated for the polysome attachment protein. Activities, depending on cytochromes P-450 and b 5 , are hampered, e.g. those of the monoxygenase system. Cholesterogenesis is derepressed. Ratios of phospholipids/cholesterol are decreased, and lipid-protein complexes, altered both in structure and function. Another distinct effect of the membrane-polysome separation is the unmasking of thiol-disulfide exchange enzymes which, in turn, stimulate the biosynthesis of proteins and of deoxyribonucleotides involved in cell replication.

Cysts, Hyperplasias and Papillomas The greatest difficulty in interpretation and classification is encountered in lesions that exhibit cysts, hyperplasias or papillomatous formation. The lesions frequently coexist with or are superimposed on the abnormalities described above. Thus it can be seen that the opportunity to designate some lesions as distinct entities is relatively rare. It is probable that the various changes are manifestations of the same syndrome, but the evidence is not conclusive. The lesions usually occur in women in the latter part of active sexual life. Unlike the syndromes described above, regression following the menopause appears to be less frequent, . . .

IN A PREVIOUS STUDY (1, 1a), the urinary excretions of the 17-ketosteroids (some of which are androgenic) and estrogens in boys and girls were determined. It was shown that the 17-ketosteroids increase gradually with advancing years in both sexes; boys having a somewhat higher level than girls particularly after 11 years of age. However, the difference in the levels between the sexes was not very great. The estrogens also increase gradually with age, with a higher level in girls, especially after 10 or 11 years of age, when a marked distinction between the sexes develops, due to the appearance of a cyclic excretion in the female. The 17-ketosteroids, as far as can be ascertained, do not have cyclic changes in excretion rates, but remain at a fairly constant level at any given age period in both sexes. In order to determine the ac curacy of the collection of the 24-hour urine specimens in these cases, analyses of creatinine were also made.

THE GLANDS of internal secretion are of great importance in childhood. Their three major functions are: to stimulate growth, to influence metabolic activities and to regulate physical metamorphosis of adolescence. The rate of growth and the resting metabolic rates (factors largely influenced by the secretion of the endocrine glands) have been discussed by others, but very little work has been done previously in regard to the third function. This investigation deals chiefly with the urinary excre-tion of the sex hormones, measurements which should indicate the rate of activity of the glands from which these secretions are derived. Development in normal youth is essentially a problem of normal activity of the pituitary gland and the ability of the peripheral endocrine organs to respond to its stimulation. Laboratory and clinical evidence indicate that without the normal func-tioning of this particular endocrine organ, the otherwise normal peripheral glands such as ovaries and testicles remain quiescent and ...

INTRODUCTION THE development of a method for the colorimetric estimation of urinary steroid alcohols (3) and a fluorometric method for the estimation of urinary estrogens (2) makes it possible to carry out simultaneous studies of these components as well as ketosteroids in the urine of patients under various types of hormone therapy. This report will be concerned with the effect of the administration of dehydroepiandrosterone1 and testosterone on the urinary excretion of ketosteroids, steroid alcohols and fluorogenic phenols2 (FP) in a series of 6 patients with cancer of the breast (female), 1 patient with cancer of the prostate gland and 4 patients with rheumatoid arthritis.3 METHODS Twenty-four-hour urine specimens were collected during preliminary control periods, periods of therapy and post-treatment control periods. Daily determinations of creatinine were performed to check completeness of the collections. An aliquot of each 24-hour specimen was hydrolyzed by boiling for ten minutes with J 5 volumes ...

In previous communications the life expectancy of patients with cancer of the breast (1), oral cavity (2), and gastro-intestinal tract (3) has been discussed. In the present paper the life expectancy of patients with carcinoma of the genito-urinary tract will be considered. The discussion will include cancer of the vulva, vagina, cervix and fundus uteri, ovary, penis, testicle, prostate, bladder, and kidney. All cases of cancer of these organs admitted to the Collis P. Huntington Memorial and Pondville Hospitals in the years 1912–1933 have been reviewed personally. It must again be stressed that these hospitals are organized strictly for the care of cancer patients. All those with cancer that apply are admitted for treatment; many of them have only terminal care. Only those cases in which a definite history of the date of onset could not be determined or in which the diagnosis was uncertain have been omitted in the present study. In compiling statistics on age and sex incidence all cases entering the hospitals before Jan. 1, 1936, have been included. The method of calculation of the life expectancy curves was fully described in the first paper (1). No attempt to evaluate the number of five-year survivals has been made, since many of the patients did not receive their initial treatment in these hospitals.

THE INTERNAL SECRETIONS in childhood influence growth, metamorphosis and metabolic reactions. Growth rate and certain aspects of metabolism are easily studied. A different situation exists in regard to abnormalities of metamorphosis from childhood to adult life since they are not often recognized until the time when the normal changes should occur. Technics by which these processes may be more thoroughly studied have recently become available. Foremost among these is the determination of the sex hormones in the urine. In the last 6 years we have determined the levels of sex hormone excretion in children for evaluation as an index of future metamorphosis as well as for an index of abnormalities in development which had already become manifest. The information derived may thus be correlated with other data concerning these abnormalities. There are very few data on sex hormone excretion in abnormalities of childhood. This is because normal standards had not been established through childhood and puberty, and...

STUDIES in this laboratory, as yet unpublished (i), it has been de-Ftermined that the 24-hour urinary excretion of estrogens in both the male (ROM)and female child vary from day to day. In young children (5 to 10 years of age) these fluctuations are slight, but in the pre-adolescent groups they be-come more marked. Our data obtained thus far suggest that in the female child, at least, there is a cyclic excretion of the estrogenic hormones for several years before the menarche. This necessitates, therefore, the assay of a series rather than a single day’s specimen of urine in the study of the normal estrin excretion even in children. The present study was undertaken to ascertain i f there were similar variations in the daily output of the urinary androgens before puberty.

AEMLIORATION of the vaso‘motor symptoms of the menopause by the AMELIORATION use of testosterone.propionate has been reported by several investi ‘gators (1-4). Salmn (1) noted a change in the vaginal smear from the menc pausal to the cornified type, which was not found by Shorr et al. (2). Both, however, observed a decrease in the levels of FSH after treatment with testosterone became effective. It was concluded that testosterone had the same effect as the estrogens, that is, inhibition of the anterior pituitary gland. This study was undertaken to ascertain if there were changes from the pre’treatment levels of urinary FSH, androgens and estrogens, after ad‘ ministration of testosterone propionate1 to female castrates. Similar work on normal males, eunuchoids and female castrates, to be referred to later in this paper, has been reported by others during the course of these experiments. Subjects. Four women who had severe menopausal symptoms following surgical or radiation castration were selected for this...

URINARY EXTRACTS containing a mixture of 17-ketosteroids are assayed colo.rimetrically by the Zimmermann reaction using a single 17-ketosteroid as a reference standard. If the standard and the other urinary 17-ketosteroids produce significantly different color intensities, per unit weight, such assays will be subject to error. Hence it is important to ascertain whether appreciable differences in the chromogenic values of the various urinary 17-ketosteroids exist, and if these differences can be minimized. The authors have shown that the relative chromogenic values of several 17-ketosteroids depend on the alcohol and the potassium hydroxide concentration as well as the time used in the Zimmermann reaction. Essentially equivalent colors were produced under some conditions whereas large discrepancies occurred under others (Nathanson and Wilson, 1943). This work has now been expanded to include a larger number of 17-ketosteroids. Observations have been made with a series of reaction mixtures containing select...

A dolescent or puberty mastitis in the male is akin to that normally seen at the onset of breast development in young girls. In the male it usually appears between the 12th and 16th year. It is characterised by the presence of a well defined, freely movable discoid or round palpable mass of breast tissue, closely associated with the areola. The mass may vary in sise from less than 1 centimeter to 5, but as a rule is 2 to 3 centimeters. The overlying areola and nipple may be enlarged. Tenderness is not uncommon and may be the first and only sign noted by the patient. The process is usually unilateral at the onset, but may affect both breasts simultaneously or successively. Adolescent mastitis must be distinguished from gynecomastia in which the size, contour and elements approach that of the normal adult female breast; and from enlargement of the breast due entirely to adipose tissue such as is seen frequently in adiposo-genital dystrophy and in eunuchs.

THERE are a number of procedures for estimating the 17-ketosteroids in urine extracts by the use of m-dinitrobenzene in alkaline alcoholic solution. These various methods do not give similar results with the same urine extract (Friedgood and Berman, 1941; Strickler, et at. 1941). In this laboratory normal values for 17-ketosteroid excretion obtained with a photoelectric modification of the method of Oesting (1937) have been higher than those reported with some other procedures. The present study was undertaken to establish the usual magnitude of such discrepancies and the basis for these differences.2 The following methods, which represent those most commonly used for the assay of 17-ketosteroids, were selected for study. All utilize the photoelectric colorimeter. A. The Callow (1938) procedure as adapted by Langstroth and Talbot (1939a) and Talbot, et al. (1940a). B. The procedure of Holtorff and Koch (1940). C.

The production of an inhibition of the estrous cycle in the rodent has been reported repeatedly with the use of various hormones as well as with other agents. The mechanism is obviously complicated, for anestrus may be produced through the inhibition of the gonadotropic hormones or it may occur as a result of a direct action upon the ovary itself. This phenomenon is of clinical interest since it may explain one of the causes of functional amenorrhea in the human, and indicate its proper treatment. On the other hand, if the mechanism can be sufficiently understood it may prove of value in the treatment of uterine hemorrhage of functional origin by enabling one to produce a temporary amenorrhea when it is desired. It is our purpose in this communication, therefore, to present what we believe may possibly be one of the fundamental factors concerned in the production of amenorrhea. It is an established fact that a large number of patients who lactate following parturition have periods of amenorrhea varying fr...

PREVIOUS STUDIES in this laboratory (1, 2) have indicated that testosterone propionate acts directly upon the vagina and uterus of the immature female rat, and stimulates the ovary indirectly by way of the hypophysis (1) even in the absence of the adrenals (2). Moreover.it was shown that testosterone was capable of stinvulating the thyroid and parathyroid glands of the same type of animal (3). This stimulation was manifested by increased mitotic activity and by histological evidence of functional activity. The mechanism by which this occurs is probably an indirect one via the pituitary gland. It is the purpose of this communication to record the effect of testosterone upon the mitotic activity of the adrenals in the intact immature female rat. Colchicine was used in addition to testosterone because of its ability to ternporarily inhibit or prolong the mitotic cycle in early metaphase.

ConclusionsTestosterone stimulates directly the growth of the uterus and the vaginal epithelium of the immature rat. There is a qualitative difference only in the uterine response in the intact and ovariectomized animal. It does not act directly on the ovary but stimulates it indirectly by way of the anterior hypophysis, resulting in follicle maturation and corpus luteum formation. As a result of corpus luteum formation from hypophyseal stimulation, the Fallopian tubes may show growth activity.

ConclusionTestosterone propionate is capable of stimulating the thyroid and parathyroid glands of the intact immature female rat. This stimulation is manifested by increased mitotic activity and by histological evidence of functional activity.

While producing cirrhosis in rats by high fat, low choline diets, the authors observed that the livers of female rats showed less severe lesions than those of males. Similarly, the kidneys of young females appeared to withstand the effects of low choline diets better than the kidneys of young males. These findings are in agreement with those first reported by Griffith (1940). In an effort to explore the factors involved in these sex related differences, injections of estrogens and androgens were given to groups of both males and females on the experimental diet. The results indicate that the renal and hepatic lesions which develop after feeding rats a high fat, low choline diet may be altered by hormonal injections. The present findings, plus those reported in a preliminary note (1947) complement the work of Gyorgy, Rose, and Shipley (1947, 1949).

Chairman Smith: In their approach to breast feeding, as to religion, pediatricians might be classified in 3 groups. There are the firm believers, with serene faith that all women ought to nurse their babies because "breast feeding is best feeding." At the other extreme, certain agnostics hold that it makes no important difference whether a baby is breast fed or given a formula. Much the most numerous are the third group, who would be glad to have a faith to stand up for if the rational basis of such a faith were revealed to them. These conscientious physicians, anxious to give sound scientific advice, find themselves falling back among traditions and impressions, in the absence of modern factual knowledge. Much new data concerns only premature infants, for whom it is quite possible that Nature did not design human milk. Obviously we need facts. Are the antibodies in human milk significant? Does it protect against neonatal diarrhea? Does suckling cause uterine involution? What constitutes optimum growth in infancy? Does it result with artificial feeding? Without the answers to these and other questions the subject escapes into psychologic and emotional fields since it cannot be properly tackled in physiologic territory. Indeed whether a mother will nurse her baby is now usually decided psychologically rather than physiologically. If 72% of New Hampshire babies leave the maternity hospital on bottle feeding only, compared to 10% of those in South Carolina, the psychology of South Carolina women, and of their doctors, must differ from that of those in New Hampshire.

1. 1. A group of cases have been presented which have a clinical picture similar to that of acute appendicitis, but which have been proven by laparotomy to be acute mesenteric lymphadenitis. 2. 2. Hemolytic streptococci have been isolated from every one of the throats of these patients that have been cultured. The same organism has been isolated from a small percentage of the nodes removed and studied. 3. 3. The possibility of this condition being a hematogenous spread from such a focus as acute respiratory tract infection has been advanced. Spread by “Durchwandrung” is not believed the pathway. The appendix itself is not believed the primary factor. 4. 4. While very careful observation is advised, exploratory laparotomy should be done if an acute appendicitis cannot be definitely and completely ruled out, as the risk is much less than having a suppurative appendix rupture. We are indebted to the Bacteriological Department of the Michael Reese Hospital for the bacteriological examinations.

ConclusionNutrition of the animal is an important factor in the effects noted on the breasts of hypophysectomized rats after injection of estrogenic hormone. It is probable, however, that this hormone exerts a part of its effect on the breast by way of the hypophysis.

THERE HAVE BEEN a number of papers in recent years discussing the sible influence of estrin on blood pressure. Daniel, Crainicianu, and Mavromati (i) reported drops in blood pressure as great as 50 mm. of Hg lasting an hour or longer following the intravenous injection of 1 cc. of menformon (Hogival), (highly purified estrogen), in women. They stated that no drops occurred in men or male cats, whereas an immediate hypo′tension was obtained in female cats. Crainicianu (2) confirmed this work using 100 u.s. (mouse units) of folliculine (Hogival) intravenously in human beings. Melchionna (3) obtained no change in the blood pressure of 9 dogs under nembutal or ether anaesthesia from the intravenous administration of 250 R.U. of crystalline theelol dissolved in 0.25N sodium hydroxide diluted with saline. Ay man (4), in a careful clinical study observed no effect of theelin on the blood pressure of 10 patients even after treatment over a period of months; the largest doses, however, totalled only 300 R.U. by mo...

EVANS AND SIMPSON1 have reported that large doses of pregnancy urine hormone (PU) will increase the ovarian weights of immature rats much beyond the limit of 60 or 70 mg. originally given as the maximum stimulation, when administered over a period of 4 or 5 days. The same ovarian response was obtained when they used comparable doses of the gonadotropic substance found in the urine of men with testicular neoplasm. A further comparison of the gonadotropic substances from these two sources showed that neither increased the weight of the testes of pigeons when given in small doses but both had very pronounced effects when given in doses above 5000 R.U. These facts support the general belief that the active substances from these two sources are identical. We have studied the gonadotropic material from a case of testicular chorioepithelioma and have found, in agreement with Evans and Simpson,1 that the ovarian weights increase very gradually with dosage up to 58 mg., when less than 2500 u are given. When 5000 u...