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The undersurface of the epidermis covering the tip of the nipple is similar to that of tactile surfaces; at the sides it is more shallow than in the areola where it is evenly reticulated. These are the distinctive structural signatures of the areas. Both the nipple and the areola are glabrous and both have galactophores and sebaceous glands. In the nipple these open only at the tip and are grouped mostly toward the center. In the areola are the glands of Montgomery, accompanying sebaceous glands and a few scattered eccrine sweat glands. Hairs of different sizes are always present at the periphery of the areola but not in its middle. Both the galactophores and sebaceous glands contain variable numbers of melanocytes among their epithelial cells. Sensory nerve end organs are found only at the tip of the nipple and sensory nerves are loosely wrapped around the galactophores, lactiferous ducts, and some lactiferous sinuses. Both the nipple and the areola have a bountiful framework of elastic fibers that supply rigidity and support, anchor smooth muscle fibers, keep the lactiferous ducts and sinuses from collapsing, and attach the epidermis to the dermis. Elastosis frequently takes place in the nipples and areolae, even at comparatively early ages. The nipples and areolae of women, men, girls, and boys are qualitatively identical but quantitatively different.

Our knowledge of the presence and behavior of glycogen in normal and pathologic human skin has steadily progressed during the last few years. Yet, investigations of glycogen during the various phases of development of the skin of man have been few and fragmentary (1-8). It is well known that glycogen is abundant in the skin during the first fetal months, and that it tends to disappear after the fifth month, remaining only in small quantities in the cells of the malpighian layer. Glycogen persists, however, in the sebaceous glands, eccrine sweat glands, and in the external root sheath of the hair follicles. The presence of glycogen in the skin during fetal and postnatal life undoubtedly has a functional meaning, it being of primary importance in tissue metabolism (9, 10, 11). It has seemed to us important to reinvestigate systematically the distribution of glycogen in the skin of the fetus, making parallel investigations of the distribution of amylophosphorylase, the catalytic action of which is indispendable for the metabolic utilization of carbohydrate.

Eccrine sweat glands in paraffin sections of human skin fixed in neutral buffered formalin nearly always contained acidic carbohydrate detected by the colloidal iron stain, and to a less extent by Alcian blue 8 GX. Additional histochemical procedures designed to detect sulfated carbohydrates showed none. The acidic carbohydrate demonstrated in eccrine sweat glands was presumed to contain only carboxyl groups. As incubation of tissue sections in neuraminidase abolished stainability of the acidic carbohydrate with colloidal iron, the material removed was considered to be a sialomucin. To the best of our knowledge, the identification of the acidic mucin in human eccrine sweat glands as sialomucin has not been reported previously.

In this paper we report the changes that occur in the responses of the eccrine sweat glands on the volar surfaces of the digits of Lemur mongoz to sudorific drugs after the nerve trunks to the hand were severed. Although the pharmacological properties of these glands in the intact hand have some resemblance to those of man, their behavior after denervation is different. Lemur mongoz, a relatively primitive mammal, low in the Order of Primates, and a distant relative of man, has eccrine glands only on the volar surface (1). Since these animals are difficult to obtain, we have had to limit our observation to 4 animals.

INTRODUCTION In recent years much attention has been focused on the human eccrine sweat gland by both clinical and basic science investigators (1-14). The clinician is aware of the role of the sweat gland in the production of both general and cutaneous disease. The physiologist and the chemist have studied the normal and the alterations from the normal of the functions of the gland and of its secretions. Pathologists have been concerned primarily with tumors of the sweat glands and occasionally with alterations in structure as they pertain to clinical disease. The present trend is to correlate the normal and the abnormal variations of the physiology and chemistry of the sweat gland with its histochemistry and histo-logic structure.

The eccrine sweat glands are innervated by cholinergic postganglionic fibers of the sympathetic system. This anomalous situation has been amply established and both systemic and locally administered sympatholytics, or anticholinergics, have been shown to inhibit eccrine sweating. There has long been the desire to inhibit locally hyperhidrosis with topically applied anticholinergics without notable success to the present time.

The acrosyringium, the intraepidermal ec-cine sweat duct unit, is functionally and biologically independent of the surrounding epidermis. Tumors originating from the acrosyringium were unknown until ten years ago when Pinkus et al.described the eccrine poroma (1). Since then it has been thought that the epitheliomatous (poroepithelioma) or carcinomatous (porocarcinoma) differentiations of the acrosyringium might exist. By electron microscopy, it has become possible to reveal distinctive embryogenesis and structural differences between the acrosyringium and the dermal eccrine sweat duct (2, 3, 4).

Although the physiologic effects of repeated episodes of profuse sweating have been extensively studied in man, nothing is known of the possible anatomic alterations which may occur in the eccrine sweat gland as a result of these stimuli. It has recently been shown, however, that as a result of a single, prolonged episode of profuse sweating the human eccrine sweat gland undergoes characteristic cytologic changes (1). In addition, an orderly, progressive sequence of recovery from these changes has been observed (2).

The human eccrine sweat duct may be divided into two parts. [1] The “dermal sweat duct” (that portion that lies within the dermis) and [2] the “epidermal sweat duct unit” (that portion that lies within the epidermis).

Sweat glands in a small area of skin on the volar surface of the forearm were stimulated twice daily with intradermal injections of acetyl-B-methylcholine. Training, resulting in an increased sweating response to the standard dose of drug, occurred in all of the five men and five women subjects. Sweat samples were collected on filter papers in an unventilated sweat capsule and analyzed for sodium and chloride. Both of these minerals increased in concentration as the sweat rate increased. In eight subjects the increase in sodium was that which would be predicted on the basis of enhanced activity of the sweat glands involved. In two cases the sodium increased less than would be expected if the increased sweat were due to training alone. This was attributed to the recruitment of additional sweat glands, which resulted in a greater volume of sweat with less tonicity than expected. The women were less sensitive to the standard dose of acetyl-B-methylcholine used throughout the training period. The data from men and women were significantly different on days one and two and on days nine and ten. However, by the 17th and 18th days of training there was some overlap in data from the two groups.

The epidermis is the ultimate source of the cutaneous adnexa, giving rise at about the third month of fetal 4ife to the eccrine sweat glands and the primary epithelial germs from which in turn are differentiated the pilosebaceous unit and the apo-pilosebaceousTtnit. Classical teaching has, until recently at least, denied or been unaware of the epidermis' potentiality to form adnexa in adult life, particularly in respect to the creation of new hair follicles. Recently, the genesis of new hair follicles has been incontestably demonstrated in adult rabbits by Breedis (1), supporting older but largely ignored evidences of a less conclusive character; it is our intention in this paper to provide an example of this in adult humans.

In paraplegics sweating was evaluated both above and below a lesion of the spinal cord. Sweating was measured on the forearm and thigh during both thermal stress or repeated injections of methacholine. The results were as follows: (1) Three traumatic paraplegics did not sweat in response to the thermal stress in decentralized areas. (2) Two post-polio subjects responded to thermal stress on both the arm and leg. (3) Six of seven subjects tested showed training on both the arm and leg. Examples of increased sweating due to recruitment, enhancement, and to a combination of these two processes were observed. (4) The predominant process (i.e. recruitment or enhancement) contributing to the increased sweating response during training was the same on the arm and leg of a given individual even in instances where the leg did not respond to thermal stress.

Ever since the investigations of Robinson (1), Pollitzer (2) and Schlachta (3), it has been accepted that all forms of miliaria are associated with occlusion of the outlets of the eccrine sweat glands followed by an inability of the affected gland to deliver sweat to the surface. This occlusion results in reduction (hy-pohidrosis) or absence (anhidrosis) of sweat on the skin surface. (Orentreich, Berger and Auerbach (4) noted anhidrosis to persist 14 days following the application of a 1.5 inch square of plastic wrap to the midback for a period of 6 days. In their study they did not use a heat stress and did not mention the appearance of miliaria.) To our knowledge, there are no systematic studies of the relationship of anhidrosis to the severity of miliaria, nor has the duration or degree of anhidrosis been determined following miliaria produced over relatively large skin areas.

In previous papers, we reported the pharmacological and histochemical properties of the eccrine sweat glands of the mongoose lemur and the changes that occur in these properties after denervation (1, 2). Only some of the data that we obtained in that animal somewhat resembled the data obtained in man.

An anticholinergic agent (AHR-483)1 has been investigated for its property of suppressing or totally inhibiting eccrine sweat gland function when applied topically-over large areas of the body-without inducing other significant local or systemic side effects.

The effects of mecholyl, epinephrine and ouabain on glucose metabolism were studied in freshly dissected human and monkey paw eccrine sweat glands. Both showed active glycolytic activity which was further stimulated by mecholyl and epinephrine. Ouabain inhibited unstimulated as well as mecholyl or epinephrine-stimulated glycolysis and mecholyl-stimulated 14 CO 2 production. Anaerobic incubation and the addition of KCN markedly enhanced lactate production. Mecholyl and lower concentrations of epinephrine stimulated both 14 CO 2 and lactate production. Higher concentrations of epinephrine stimulated lactate production but markedly suppressed 14 CO 2 production. A possible link between energy production and glandular secretion was discussed.

The ways in which an organ reacts to various experimental stresses provides useful information in understanding its behavior in disease. Much has been learned of the biological potentialities of skin by following the changes in deliberately produced wounds (1, 2, 3, 4, 5). By restricting the injury, Lobitz et al have been able to study the individual responses of particular structures, such as the pilosebaceous apparatus (6) and the eccrine sweat unit (7, 8, 9). The objective of the current study is to describe the reactions in buried human auto-transplants.

INTRODUCTION In a previous study (1) of injury to human skin wherein the entire epidermis was removed, three major stages of repair of the eccrine sweat duct were identified: A stage of degeneration and a preparation of the environment for the regeneration to follow; A stage of active cell migration and proliferation; A stage of reorganization and orientation.

Sweating may produce depletion of stainable glycogen from the cells of both the duct and the secretory coil of the human eccrine sweat gland (1, 2, 3). A slight decrease in the amount of this glycogen has also been found in the secretory cells of the Japanese monkey (Macaca fmcata) (4). In the rhesus monkey, as in man, at * least some of the energy used to produce sweat may come from the breakdown of glycogen stored in the clear cells of the secretory coil.

Studies of quantitative and qualitative changes in the eccrine sweat secretion have recently concerned themselves with not only the changes in the concentration of sweat electrolytes (1, 2, 3, 4), the regulation of water output onto the skin surface in relation to homeostasis and skin vasomotor regulation (5, 6, 7, 8) but also in relation to electrophysical phenomena on the skin which are either directly or indirectly influenced by the quantity of water and electrolytes contained therein (9, 10, 11, 12).

The purpose of this study was to apply whole mount technic (2) as well as routine tissue histologic technic to a microanatomical disturbance in the intra-epidermal eccrine sweat duct which results in the clinical picture of miliaria crystallina. Recent studies using fresh, unfixed skin have shown clearly that the terminal part of the eccrine sweat duct has its own intrinsic walls of keratinized cells (2, 9). The luminal lining consists of periodic acid-Schiff or P.A.S. (Hotch-kiss-McManus)-positive material throughout the course of the duct. Recently this or a similar material has been suggested by Cormia (1) as a factor in the production of sweat retention as seen in various dermatoses. Therefore, a second purpose was to study this material in miliaria crystallina lesions. In addition, with this latter purpose in mind, experimental obstruction of the ducts within the footpads of cats has been produced and examined microanatomically.

Although the cytologic changes occurring in the eccrine sweat gland as a result of profuse sweating have been extensively studied in recent years (1, 2, 3), no attempts have been made to correlate these changes with the physiologic function of the gland under varying conditions. It seems reasonable to assume that such correlations can be made based on the observations that after repeated episodes of profuse sweating not only is the cytologic structure of the sweat gland altered but its function as well. It has been shown, for example, that acclimatization to heat manifested by a diminished sodium excretion by the sweat gland is accompanied by a decrease in the number of large pale cells within the eccrine secretory coil (4). It was, therefore, concluded that the large pale cell is in some way concerned with sodium excretion by the sweat gland.

The epidermal portion of the duct of the eccrine gland is morphologically distinct from the epidermis proper. This was recognized by early histologists such as Kolliker (1). In more recent times Pinkus (2) emphasized the integrity of the eccrine duct as it coursed through the epidermis. This observation was confirmed and extended by the histologic studies of Lobitz, Holyoke and Montagna (3, 4) on normal skin and on skin subjected to mechanical stress. In their work Lobitz and his co-workers defined a structure which they called the “epidermal eccrine sweat duct unit” and showed that it had individual staining properties and physiologic capabilities.

By the use of a sensitive and specific double antibody radioimmunoassay, immunoglobulin E was demonstrated in sweat from 6 of 11 healthy volunteers; the concentrations of IgE ranged from 1 to 3.9 ng/ml of sweat. Six of seven patients with dermatitis and elevated levels of serum IgE also had high IgE levels in sweat; the highest IgE value in sweat was 75.5 ng/ml and was noted in a patient with atopic dermatitis. Thus, all the main immunoglobulin classes can be demonstrated in eccrine sweat.

Of the several methods for estimating the distribution and activity of the eccrine sweat glands which utilize the starch-iodine reaction (1-4), the technic of Randall (2), and Wada (3) are the simplest. In the former procedure, direct prints of the sweat pattern are made by pressing starch containing bond paper against an iodine treated test site. One looks at the paper not the skin for the result. The droplets are not seen as they form. The print is a static representation. Moreover, evaporation of tiny droplets and fusion of larger ones before “printing” are disadvantages. Wada's method, on the other hand, permits detailed visualization of the unfolding pattern of sweat formation. In this technic, castor oil, as a vehicle for suspended starch, serves to trap the accumulating sweat. The entrapped droplets are then seen as discrete, enlarging blue-black puncta. One can directly watch the dynamics of sweat formation on the skin itself but no permanent record is afforded for later study. When bond paper is applied to these areas, only meaningless smudges are obtained. Aside from the expense, photographs do not give the desired clarity because of light scattering from the oily surface.