Ephraim Shorr

Modification of the effects of immobilization upon metabolic and physiologic functions of normal men by the use of an oscillating bed

Abstract A study was made of the influence of an oscillating bed on the metabolic and physiologic disturbances associated with immobilization. The subjects were three normal healthy young men. The investigation was carried out on a metabolism ward during control (four to five weeks), immobilization (five weeks) and recovery (five to six weeks) periods. The dietary intake was constant. During the immobilization periods the subjects were in bivalved plaster casts extending from umbilicus to toes. One year previously the three subjects studied had participated in an experiment identical with the present study except that they had been immobilized in standard (fixed) hospital beds. During immobilization in the oscillating bed: 1.1. Nitrogen excretion increased in the same general pattern as in the fixed bed experiment; but in two of the subjects nitrogen loss was approximately half as great as during an equal period of immobilization in the fixed bed. 2.2. The loss of calcium, chiefly in the urine, was, on the average, half as great as during the same period in the fixed bed. 3.3. The loss of phosphorus was significantly less in two of the subjects than during the same period in the fixed bed. 4.4. Although urinary citric acid, pH and urine volume did not appreciably change, the significant reduction in urinary calcium and phosphorus losses would render the precipitation of calcium phosphate in the urinary tract less likely than during immobilization in a fixed bed. 5.5. There was good correlation between the excretion of urinary total sulfur and nitrogen on the basis of the ratio in which they exist in muscle. The correlation between nitrogen and phosphorus on the same basis was less good, between nitrogen and potassium poor. 6.6. Creatine tolerance tests indicated that creatine metabolism was significantly less impaired than during immobilization in the fixed bed. The decrease in muscle mass and strength of the immobilized limbs was also less than during an equal period in the fixed bed. 7.7. Changes in basal oxygen consumption were not significant. 8.8. The deterioration produced by fixed bed immobilization in the mechanisms essential for adequate circulation in the erect position (as measured by tilt table tests) was largely prevented. 9.9. Measurements of venous pressure in the foot veins during oscillation revealed an average change in pressure of 140 mm. of water with each change in position of the bed. A rhythmical shift was observed in the average level of the diaphragm with each change in position of the bed, without significant alteration in the pulmonary minute ventilation. 10.10. Changes in urinary 17-ketosteroid excretion and in serum calcium levels were not significant. 11.11. As in the fixed bed experiment, there were no significant alterations in blood coagulation studies, circulation time, heart size or electrocardiograms. During the recovery phase most metabolic and physiologic functions returned to control levels or became re-stabilized more rapidly than following immobilization in the fixed bed. Following recovery from the oscillating bed experiment, one subject was re-immobilized in a fixed bed for two weeks. The results duplicated closely the changes observed during the first two weeks of his first immobilization in a fixed bed a year previously.

Hepatorenal Factors in Circulatory Homeostasis IV. Tissue Origins of the Vasotropic Principles, VEM and VDM, Which Appear during Evolution of Hemorrhagic and Tourniquet Shock

Studies were carried out in dogs and rabbits subjected to hemorrhagic and tourniquet shock to determine the tissue origins of two newly described vasotropic principles, VEM and VDM. The vasoexcitor principle, VEM, predominates in the blood during the initial compensatory stage and was traced to the kidney. The vasodepressor principle, VDM, prevails during the decompensatory phase and was found to originate in the liver, skeletal muscle and spleen. During the decompensatory phase, there was a progressive deterioration of the hepatic mechanisms for inactivating VDM. Sequential tissue hypoxia during shock is probably responsible for the formation of these vasotropic principles and for the deterioration of the hepatic VDM inactivation system. Special emphasis is placed on the effects of local concentrations of VDM within the liver and on the resultant diversion of blood from the general circulation into the splanchnic viscera.

Neutralization of Ovarian Follicular Hormone in Women by Simultaneous Administration of Male Sex Hormone.

Conclusion Studies of vaginal smears and biopsies indicate that the male hormone (testosterone propionate) is able to neutralize, in women, the effects of estradiol on the cornification of the vaginal epithelium.

The Use of Androgens in Women

Publisher Summary This chapter describes the use of androgens in women that has resulted in important contributions to the knowledge of the physiology of the reproductive system in the human and also to the more effective management of a variety of clinical disorders. Although some clinical applications may prove only of present value, eventually to be superseded by measures that are more appropriate to, or specifically corrective of, the underlying defects, others may retain a permanent place in therapy by virtue of certain unique actions exerted by androgens. It has been possible to relate a number of their clinical effects to well established actions of androgens in women; on the other hand, there still remain many important areas of uncertainty, which await clarification. The property of androgens in inducing profound alterations in a variety of important metabolic functions is receiving much attention not only for its scientific interest but also because of its therapeutic implications.

Action of Gonadotropic Hormones in Amenorrhea as Evaluated by Vaginal Smears.

Summary The desirability of a reclassification of the amenorrheas based, in part, on the vaginal smear picture has been suggested. Definite smear changes indicative of ovarian stimulation and resembling the normal cycle have been induced in amenorrhea by means of gonadotropic hormones. The vaginal smear should afford a simple and sensitive method for evaluating the effects of such hormones in the human subject.

Effect of Concomitant Administration of Estroens and Proesterone on Vainal Smear in Man.

Of the changes in the vaginal secretion during the menstrual cycle 1 those occurring in the first half concurrent with the growth and ripening of the ovarian follicle are most clearly defined and best understood. The demonstration in this laboratory 2 that they are similar to the smear changes induced in menopause and amenorrhea by the administration of estrogens, indicates that during the first half of the cycle the vaginal epithelium and secretion are largely, if not entirely, under the control of the estrogenic hormones. The peak effect of the estrogens as seen in the fully expressed “follicular picture” induced after menopause can, therefore, serve as an index of the extent of spontaneous follicular activity during the normal cycle, and affords a simple histological measure of ovarian function. It can also be employed as a guide for replacement therapy with estrogens 2 and as a measure of ovarian stimulation by gonadotropic agents. 3 The changes in vaginal smear during the second half of the cycle from the time of ovulation up to the next menstruation are less clear cut and more difficult to evaluate. 1 The lack of uniformity nossibly arises from the more complicated hormonal pattern of this phase of the cycle. The estrogenic titer falls from its mid-menstrual peak and, except for a brief moderate rise about a week premenstrually, gradually sinks to the low levels characteristic of the premenstruum and the menstrual phase. The progestational hormone now appears for the first time, is elaborated for a period of about 10 days and then disappears one to 3 days before the flow. 4 If, as is likely, the structure of the vaginal epithelium is a resultant of the interaction of both groups of hormones, any variation in the tempo or the extent of their production could be expected to vary the cytology of the vaginal secretion.

Sources of Energy for Intestinal Smooth Muscle Contraction

Summary A number of substances have been studied with respect to their influence on the contraction of excised segments of rabbit small intestine. The results have been discussed in relation to present concepts of intermediary metabolism. Particular attention has been given to fatty acids, from propionic through pelargonic. With the exception of propionic, all appear to provide energy for smooth muscle contraction; and the characteristics of their behaviour were compatible with the concept of β-oxidation.

Action of Ovarian Follicle Hormone in Ovarian Insufficiency in Women as Indicated by Vaginal Smears.

The treatment of women with ovarian insufficiency by ovarian follicular hormone (OFH) has fallen short of the expectations aroused by its successful use in animals. It is possible that the amounts of hormone necessary to produce comparable changes in man are so large 1 as to be out of the question except for occasional brief studies in humans. 2 On the other hand the failures may have been due to the lack of objective criteria for estimating dosage and evaluating effects; or the choice of ineffective modes of administration. The aim of this study was the development of an objective method for evaluating OFH action in ovarian insufficiency. The study of vaginal smears has been of great value in observing the effects of OFH in rodents and other mammals. Recent studies 3 have demonstrated a cycle in the vaginal fluid of the human comparable to that in animals. The applicability of the vaginal smear method to the study of the effects of OFH in the human is briefly described in this report. Fifteen women with ovarian insufficiency, following either bilateral ovariectomy or the menopause, were observed over periods of several weeks to a year. After a control period to establish the character of the vaginal smear and the absence of OFH in the urine, treatment was begun. Smears were taken regularly over long periods and at varying intervals after administration of the hormone. The dose of OFH was adjusted from time to time until changes occurred in the smear. Subjective symptoms, such as hot flushes, headaches, nervousness, mental depression, and libido were also noted.

Influence of thyroid administration on creatin metabolism in myxedema of adults.

Little is known of the creatin metabolism of adult myxedema other than the absence of spontaneous creatinuria. In children with cretinism or hypothyroidism, the physiological creatinuria of childhood is absent. 1 , 2 When thyroid substance is given to such children, large amounts of creatin appear in the urine. 1 , 2 This effect has been interpreted as a restoration of the normal creatinuria of childhood. It is not known, however, how long the creatinuria persists with continued administration of thyroid substance in amounts sufficient to maintain a normal basal metabolism. We have studied the creatin metabolism of 2 typical cases of spontaneous adult myxedema. Their diet was creatin-creatinin-free, and adequate in calories and protein. The ability to retain ingested creatin (1.32 gm.) was tested from time to time. After a control period, thyroid substance was administered in amounts sufficient to restore and maintain a normal basal metabolism. The usual improvement in signs and symptoms took place. Six cases of myxedema following total ablation of the thyroid∗ were studied in the same way, except that no thyroid substance was given. Our findings in spontaneous myxedema are given in Table I and Chart 1. Results. In agreement with other workers, we found no creatinuria in spontaneous adult myxedema. Creatinuria was also absent in myxedema following total ablation of the thyroid. In both groups the retention of ingested creatin was normal. In spontaneous myxedema small doses of thyroid substance caused a pronounced creatinuria and a diminished tolerance to ingested creatin. This was observed before any elevation in the basal metabolism. In one case, at the height of the creatinuria, administration of glycine resulted in an excretion of extra creatin.

Hepato-Renal Factors in Circulatory Homeostasis. II. Disappearance of Hepatic Vaso-Depressor Material Following Intravenous Administration

Summary In vitro studies have shown that the vasodepressor principle, which appears during the hypo-reactive stage of shock and results from the anoxia of liver and skeletal muscles, can be inactivated under aerobic conditions by healthy liver slices. The present study was concerned with the mechanisms by which endogenous and exogenous VDM are removed from the circulation of the living animal. The exogenous VDM was concentrated and purified from saline extracts of anaerobic beef liver. The endogenous VDM was released into the blood following liver anoxia produced by temporary occlusion of the hepatic artery in a partially eviscerated preparation. Two mechanisms for VDM removal were revealed: (1) its inactivation by the healthy liver; (2) its excretion into the urine by the normal kidney. A preliminary period of hepatic anoxia rendered the liver incapable of inactivating VDM in vivo, presumably through anoxic damage to the hepatic enzyme system for this function. This situation is analogous to the progressive impairment of the VDM inactivating mechanism in the liver which develops during the course of shock and which is considered responsible for the perpetuation of the hypo-reactive state of the peripheral vascular system. The loss of the renal excretory function for VDM during hypo-reactive shock deprives the animal of an important means of clearing the blood of VDM and thereby aiding in liberating the vascular bed from this decompensatory vasotropic principle.