Human benign prostatic hyperplasia: a stromal disease? New perspectives by quantitative morphology.

Stereology is of great value for better understanding the pathomorphogenesis of benign prostatic hyperplasia (BPH) and the hormonally controlled mechanism of abnormal overgrowth of the prostate gland, especially the stromal component. In human BPH a fourfold absolute increase of the stromal part and a nearly double increase of the glandular part is indicated. The relative and absolute increase of the stromal part is surprisingly constant in spite of variation of human BPH. Stromal overgrowth can be viewed as a central feature of BPH implicating altered mesenchymal-epithelial relationship. At the ultrastructural level in man and dog the volume density of the secretory droplets and lysosomes of the glandular cells is reduced. Stereology data confirm furthermore the activation of the smooth muscle cells suggesting an induction of stromal growth possibly induced by estrogen and/or androgen and an important role in glandular-stromal interactions.

Endometrial morphology and peripheral hormone levels in women with regular menstrual cycles.

Endometrial biopsies from 90 women with regular menstrual cycles and a hormonal profile compatible with normal luteal function were morphometrically assessed using 11 different indices and the results were plotted in 48-hour periods around the day of the luteinizing hormone (LH) surge (LH +/- 0). The endometrial dating reached its highest significance from days LH -3/-2 to days LH +7/+8, when the changes occurred with a high degree of regularity regardless of the length of the preovulatory and postovulatory phases. It is proposed therefore that the dating of the endometrium should be related to the LH surge rather than to the "ideal" 28-day cycle. The results also seem to suggest the existence of a regulatory mechanism for the synchronization of follicular maturation and midcycle endometrial development. Further study of the factors involved in this mechanism may result in a better understanding of certain forms of unexplained infertility.

Human skin grafts on nude athymic mice: a light microscopic stereological study.

A morphometric procedure is presented, which allows quantitative information to be obtained from the epidermis at the light microscope level. The application of this procedure to human skin grafted to the nude mouse revealed acanthosis of the grafted epidermis compared to the original donor skin. All epidermal layers were thicker, but the increase in the granular layer was especially marked. The ratio of the basement membrane surface to the epithelial surface showed no significant change. A possible explanation for the acanthosis of the graft might be the higher mechanical stress on the nude mouse compared to the original site on the abdomen. This adaptation of the grafted epidermis does not limit the usefulness of this animal model for dermatological research, when it is assessed by objective methods, allowing statistical comparison as described here.

Morphologic findings in central bronchi correlated to lung function data in obstructive airways disease.

Quantitative analyses of morphologic findings are the condition of clinico-pathological correlation studies. These quantitative analyses are possible by morphometry. The present correlation study shows that morphometry may therefore contribute to understanding the pathogenesis of obstructive airways disease: decreasing bronchial lumen and increasing volume of grandular ducts are correlated to increasing airways resistances (clinical parameters: RAW, FEV1). Increasing volume of bronchial muscles is correlated with resistance of airways at quiet breathing (RAW) and less with increasing residual volume (RV). Increasing volume of bronchial glands and glandular ducts is correlated with increasing resistance at forced expiration which is clinically shown by decreasing FEV1. These findings can be interpreted as follows. Airway resistances are mainly influenced by airway narrowing. At quiet breathing, muscle constriction is an additional cause of increasing airflow resistance due to bronchial narrowing. At forced expiration, however, mucus plugs probably limit the airflow because thickening of bronchial glands points to increased secretory activity. Until now it is not possible to understand why bronchial muscle volume correlates with residual volume.

A stereological study of adrenocortical cells in spontaneously hypertensive rats (shr).

The ultrastructure of SHR (Spontaneously Hypertensive Rats) fasciculata cells was compared descriptively and quantitatively with that of nonstimulated fasciculata cells of Wistar rats using sterological methods. The volume and surface densities are expressed per cm3 of cytoplasm. The smooth endoplasmic reticulum in the SHR was significantly increased compared to the control animals (surface density : 28%, volume density: 35%). Mitochondria volume remained unchanged although the inner mitochondrial membranes were significantly reduced (37%). An attempt was made to draw up a relation between sterological and biochemical data of steroid synthesis within the fasciculata cell. A genetically determined enzymatic defect in the early steps of the transformation of cholesterol to pregnenolone may exist at the level of the inner mitochondrial membrane. Whether this altered steroid metabolism is important to the etiology of hypertension in the SHR requires further investigation.

Stereological study of the zona fasciculata of the adrenal cortex in stress situations (hypothermia, catabolism).

The ultrastructure of the rat fasciculata cells in stress situations, such as catabolism and hypothermia was compared descriptively and quantitatively by stereological methods with that of the nonstimulated rat fasciculata cell. The volume and surface densities are expressed per cm3 of cytoplasm, mitochondria and smooth endoplasmic reticulum. Furthermore, absolute values are given. In both stress situations the volume density of the mitochondria compared to the controls is enlarged significantly (H: 37% CA: 50%). The significant increase of the average single mitochondrium of the fasciculata cell (H: 58% CA: 58%) shows a real growth of the mitochondria in these stress situations. Also the surface density of the mitochondrial inner membranes--the mitochondrial enzymes for steroid genesis are partly located in these membranes--shows a significant increase (H: 31%, CA: 84%). Whereas the volume density of the smooth endoplasmic reticulum remains unchanged, the surface density is significantly raised (H: 44%, CA: 60%). An attempt was made to draw up a relationship between stereological and known biochemical data of steroid genesis within the fasciculata cell. An activation in both stress situations could be observed. The stereological data reflect a subcellular reaction pattern, which is similar to exogenous ACTH administration, thus indicating an endogenous ACTH liberation due to these stress conditions.

Do's and don'ts in stereological pathology or possibilities of stereological-biochemical correlation in uropathology.

The problems and the interpretation of combined stereological-biochemical investigations in benign prostatic hyperplasia (BPH) research are discussed. As BPH is characterized by a primary stromal enlargement the role of the smooth muscle cell (SMC) is focussed. For determination of the single cell volume of the SMC several methods are applicable leading to different results. Thus interpretation of these results has to be done with caution. Finally as an example there is a discussion of a correlation of stereological-biochemical dates of human prostatic tissue samples.

The dog prostate under defined hormonal influences: an approach to experimental induced prostatic growth.

The prostate of castrated dogs following treatment with testosterone, dihydrotestosterone and androstanediol combined with 17-beta-estradiol application was analyzed by light microscopic stereology. In all three groups there is a statistically significant increase of prostatic volume and weight. There is a statistically significant increase of the relative and absolute volume of the glandular as well as of the stromal part. Seen by the absolute data there is only a statistically significant increase of the volumetric amount of the smooth muscle cells in the dihydrotestosterone and 17-beta-estradiol treated animals. Regarding tissue distribution there is no difference between the controls and the castrated testosterone and 17-beta-estradiol treated animals. Regarding the stromal part, there is no statistically significant difference between the testosterone and 17-beta-estradiol treated group and the control animals. TIn the androstanediol and 17-beta-estradiol group there is a double and in the dihydrotestosterone and 17-beta-estradiol group a four-fold increase of the stromal part. The synergistic effect of estrogens and androgens on the growth of both parts of the dog prostate--the glandular and stromal compartment--is discussed.

Stereological composition of the liver of biotin deficient and control chicks.

In an ultrastructural and stereological study the livers of 28-day-old chicks, fed either a biotin-deficient or a supplemented diet, were investigated. The biotin-deficient chicks showed the known dermal lesions and were significantly retarded in growth. About 30% less hepatocytic nuclei per unit volume liver were found in the deficient chicks than in the controls. In biotin deficiency mainly the rough endoplasmic reticulum (RER) and the mitochondria were affected. RER was diminished in volume and surface density, whereas in mitochondria only the surface densities of the outer and inner membrane were reduced. The reduction of RER is in agreement with the known reduction of protein synthesis in biotin deficiency.

[Benign prostatic hyperplasia: a stromal disease]. / Benigne Prostatahyperplasie: Eine stromale Erkrankung.

Morphometric studies show that benign human prostatic hyperplasia is a stromal disease caused by the activation of smooth muscle cells. This activation manifests itself in increased amounts of cytoplasmic organelles, which are preferably localized in the perinuclear region. Moreover, marked vesicular activity is present. Besides considerable overproduction of type I and III collagens, the architecture of the extracellular matrix is altered distinctly. In spite of strong evidence that androgens and estrogens regulate the growth of epithelial and stromal cells in the prostate and the induction of fibromuscular overgrowth in various animal models, the exact role of steroids in the pathogenesis of benign prostatic hyperplasia still remains to be elucidated.

[Surgical treatment of esophageal perforations]. / Traitement chirurgical des perforations oesophagiennes.

Spontaneous and iatrogenic esophageal perforations continue to present life threatening gastroenterologic emergencies. The results in 17 patients being treated between 1986 and 1992 are presented. In respect to localisation of the perforation, the underlying nature of the disease and the condition of the patient an early suture and wrap in all patients with benign diseases and an early esophagectomy in patients with esophageal cancer was aspired. 11 patients having been treated this way survived whereas 3 of six patients with extensive tumour burden and reduced physical state who had been treated conservatively died during the hospital stay. Thus early diagnosis and operative treatment of esophageal perforations improves patients outcome significantly.

[Salmonella eschberg--report on the isolation of a new serovar]. / Salmonella eschberg--Bericht über die Isolierung einer neuen Serovar.

The serological and biochemical characteristics of a so far unknown serovar of Salmonella subspecies I with the serological formula 9,12:d:1,7 is described. It has been named after a borough of Saarbrücken: Salmonella eschberg.