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Biomedical subjects

H Pickartz

Publications and source records attributed to H Pickartz.

At least 37 records · Page 2Linked to original sources

Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies.

The growth fraction (GF) and estrogen receptor (ER) status of 76 cases of breast cancer were investigated on frozen sections of the same tissue block by immunostaining with monoclonal antibodies (Ki-67 and anti ER antibody). In 55 cases of this series, the ER status was also determined by standard biochemical methods. Our study revealed an inverse correlation between GF and ER status. This negative relationship was most significant when both variables were determined immunohistologically in the same tissue block and less significant when GF was analyzed by immunohistology and ER status by biochemical methods. These data suggest that the immunohistologically assessed ER values characterize the receptor status of a given carcinoma better than the biochemical values, which leads to the conclusion that the immunohistologically determined close negative relationship between GF and ER reflects the actual in vivo situation of a given breast carcinoma case. However, the immunohistologic analysis also revealed that there is a proportion of exceptional cases, ie, those with a positive ER status and a large or moderately large GF. Because only half of the ER-positive breast carcinomas respond to endocrine therapy with objective remission., it is hypothesized that it might be preferentially these mentioned exceptional cases that fail to positively respond to endocrine treatment protocols.

Antibodies, Antinuclear↗

[Pedunculated polypoid gangliocytic paraganglioma of the afferent jejunal loop of a Billroth II stomach].

A mobile pedunculated polypoid tumor was endoscopically removed from the afferent jejunal loop after gastrojejunostomy of a 54-year-old patient with anamnestic evidence of intestinal bleeding. Histologically epithelial carcinoid-like as well as mesenchymal paraganglioma- and ganglioneuroma-like patterns are mixed in varying portions, characteristic for gangliocytic paraganglioma. Immunohistochemically, serotonin, neuron-specific enolase, cytokeratin, vimentin S-100 protein and neurofilament were demonstrable. Gangliocytic paragangliomas are almost exclusively observed in the second portion of the duodenum, especially around the papilla Vateri and only two have previously been reported in the jejunum. The histogenesis of the tumors is unclear, but they may probably be either hamartomas, hyperplastic or neoplastic proliferations of so called endodermal-neuroectodermal complexes. Although gangliocytic paragangliomas contain a carcinoid-like component, they behave in a benign fashion, and metastases or recidives have not been noticed. Tumors with a pedicle may be endoscopically removed without complications.

Diagnosis, Differential↗

[Hyperthecosis ovarii--a tumor-like change in androgenized females].

Hyperthecosis has been repeatedly described as a disease entity separate from polycystic ovaries (PCO) as characterised by stromal luteinisation, obligatory virilism and purely ovarian androgen hypersecretion. This study compares the findings in patients with hyperthecosis (n = 10), PCO (n = 33) and androgen-secreting ovarian tumours (n = 7). It included selective ovarian-adrenal vein catheterisation with measurement of testosterone (T), dihydro-T, androstenedione, DHEA and its sulfate, 17 alpha-hydroxyprogesterone and cortisol before and after dexamethasone; determination of free T, oestrone, oestradiol and prolactin as well as LH and FSH before and after GnRH. In histologically proven hyperthecosis, signs of virilism were absent in 6 cases. A specific hormone profile could not be identified. Mixed ovarian-adrenal androgen hypersecretion was documented in 4 patients (purely ovarian: n = 6). Ovarian T output frequently fell within the tumour range (n = 4). It is concluded that the minor differences between hyperthecosis and PCO represent only variable manifestations of the same heterogeneous disturbance of androgen metabolism. However, it is of special clinical relevance to rule out a tumour in patients with hyperthecosis.

Adult↗

Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67.

The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.

Antibodies, Monoclonal↗

Primary adrenocortical micronodular adenomatosis causing Cushing's syndrome. Effects of ketoconazole on steroid production and in vitro performance of adrenal cells.

Mild Cushing's syndrome was diagnosed in a 35 year old woman. Elevated plasma and urinary cortisol levels were unsuppressible with up to 32 mg dexamethasone per day. Aldosterone, 18-OH-corticosterone and testosterone in plasma were normal and dehydro-epiandrosterone-sulphate was low. No adrenal tumour was found by CT or adrenal venography, and bilateral cortisol secretion was demonstrated by steroid measurements in adrenal venous blood. A circadian rhythm of plasma cortisol was absent. Plasma ACTH was suppressed, even after injection of CRH, during insulin-induced hypoglycaemia and after metyrapone administration, which led to a large fall in plasma cortisol but to a subnormal rise of plasma 11-deoxy-cortisol. The clinical diagnosis of primary micronodular adenomatosis of the adrenal gland was histologically confirmed, when the patient finally underwent bilateral adrenalectomy. In vitro, the adrenal cells did not produce more cortisol and aldosterone than adrenal cells from cadaver kidney donors. In vivo and in vitro, cortisol was slightly less than normally responsive to ACTH. Intermittent treatment of the patient with 800 mg/day of ketoconazole led to a rapid fall of cortisol secretion and clinical signs of adrenocortical insufficiency. Treatment for 7 weeks with 200-400 mg ketoconazole per day reduced plasma and urinary cortisol less dramatically into the normal range. This case unequivocally documents autonomous dysfunction of the adrenal cortex in this rare form of Cushing's syndrome and the efficacy of ketoconazole in the treatment of ACTH-independent hypercortisolism.

Adenoma↗

[Microcarcinoidosis of the stomach. Diffuse hyperplasia of endocrine c ells and multiple polyp-like carcinoids].

A diffuse peptide microcarcinoidosis was observed both in a 56-year-old man with chronic atrophic gastritis and in a 33-year-old female with chronic atrophic gastritis and pernicious anaemia. Besides hyperplasia of endocrine cells at the base of gastric fundus and corpus mucosa with infiltration of the mucosal muscular layer multiple macro- and micropolyp carcinoids were present. In both cases serotonin was demonstrated immunohistochemically in the intestinal metaplastic mucosal changes, in the microcarcinoidosis foci and in the carcinoids. However, no appropriate clinical symptomatology was observed. The diagnosis can already be made by biopsy which must be deep enough and include gastric mucosa containing the mucosal muscular layer. Should gastric carcinoid be established histologically the other macroscopically normal mucosa must also be biopsied for exclusion of diffuse microcarcinoidosis as intermediate form of a multiple carcinoid. In such a case treatment consists of total gastrectomy.

Adult↗

Demonstration of hydroxysteroid dehydrogenases and testosterone in the Sertoli-Leydig cell tumor (androblastoma) tissue of the human ovary: an enzyme histochemical and immunohistochemical study.

Gynecological, endocrinological and histological tests on a 19-year-old female patient led to the diagnosis of Sertoli-Leydig cell tumor (arrhenoblastoma) of intermediate differentiation. For enzyme histochemical purposes the tumor tissue, removed from the right ovary by laparatomy, was frozen in liquid nitrogen. The following enzymes were demonstrated: nonspecific esterases, 3 beta-hydroxysteroid dehydrogenase (HSDH), 17 beta-HSDH, 11 beta-HSDH, and NADH tetrazolium reductase. Cryostat sections, prefixed with formaldehyde vapors, were used to localize testosterone production immunohistochemically with the PAP method. A large number of pseudotubules with Sertoli cells were observed; the Leydig cells in the interstitial space were often arranged in the form of islands. Strong nonspecific esterase activity weak 3 beta-HSDH activity, moderate 17 beta-HSDH activity, and strong 11 beta-HSDH activity were observed largely in the Leydig cells. Testosterone synthesis, demonstrated immunohistochemically, took place predominantly in the Leydig cells, but also to a small extent in the Sertoli cells.

11-beta-Hydroxysteroid Dehydrogenases↗

Ovarian and adrenal vein steroids in patients with nonneoplastic hyperandrogenism: selective catheterization findings.

Standardized bilateral ovarian-adrenal vein catheterization was utilized to assess directly glandular steroid release in 60 androgenized women without evidence of a functional neoplasm. Testosterone (T), dihydrotestosterone (DHT), androstenedione (delta 4 A), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), and cortisol (F) were measured by radioimmunoassay in samples obtained from a peripheral vein and the four glandular veins (all values are given as nanograms per milliliter, mean +/- standard deviation). Peripheral values were as follows: T, 0.68 +/- 0.43; DHT, 0.32 +/- 0.13; delta 4 A, 2.2 +/- 2.0; DHEA, 8.8 +/- 8.9; DHEA-S, 3137 +/- 1774; 17-OHP, 2.0 +/- 3.0; and F, 216 +/- 121. Peripheral elevations of at least one androgen were found in 80% of the 60 cases (T, 38%; DHT, 18%; delta 4 A, 50%; DHEA, 45%; and DHEA-S, 37%). Ovarian-peripheral vein gradients ( OPGs ) and adrenal-peripheral vein gradients ( APGs ) served as semiquantitative estimates of glandular secretion. OPGs were as follows: T, 0.4 +/- 1.1; DHT, 0.1 +/- 0.2; delta 4 A, 3.4 +/- 7.0; DHEA, 14.6 +/- 100; DHEA-S, -288 +/- 523; 17-OHP, 4.5 +/- 8.4; and F, -35 +/- 47. APGs were as follows: T, 0.88 +/- 1.3; DHT, 1.1 +/- 0.9; delta 4 A, 14.4 +/- 38.4; DHEA, 327 +/- 367; DHEA-S, 854 +/- 1223; 17-OHP, 20.8 +/- 41.3; and F, 1252 +/- 2023. Excess ovarian and/or adrenal androgen output was assumed in a given individual when one or more of the respective T, DHT, delta 4 A, DHEA, and DHEA-S gradients exceeded the upper 95% confidence limits of normal previously established in this laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ovarian and adrenal vein steroids in seven patients with androgen-secreting ovarian neoplasms: selective catheterization findings.

Standardized bilateral ovarian-adrenal vein catheterization was utilized to preoperatively assess glandular steroid release in seven consecutive cases of occult virilizing gonadal neoplasms. Peripheral testosterone (T) exceeded 1.5 ng/ml in all instances (range, 1.51 to 8.67 ng/ml). Endoscopy and radiography failed to locate the functional lesions. Catheterization showed a unilateral elevation of the ovarian-peripheral vein gradient for T greater than 2.7 ng/ml in six women. In the remaining patient, gradient analysis ruled out an adrenal tumor but did not facilitate lateralization of the gonadal lesion due to subselective ovarian effluent sampling. In addition to the consistent hypersecretion of T, variable excess gonadal output of dihydrotestosterone, androstenedione, dehydroepiandrosterone, and 17 alpha-hydroxyprogesterone was evident. Associated adrenal androgenic hyperfunction was documented in three subjects. Histologic evaluation of the implicated ovaries revealed three lipid cell, two Leydig cell, and two Sertoli-Leydig cell tumors, respectively, measuring between 0.6 and 2.2 cm in diameter. No correlation was found between any of the following parameters: peripheral or glandular vein steroid levels, androgen gradients, severity of symptoms, tumor morphology, and tumor size. In conclusion, appropriate application of selective catheterization may considerably reduce the frequency and extent of operative intervention.

Adrenal Glands↗

Effects of cyproterone acetate and ethinylestradiol on endometrial histology.

The influence of cyproterone acetate (CPA) containing drugs on the endometrium has not yet been investigated. Therefore, endometrial biopsies were obtained in 22 hirsute patients between day 14 and 28 of the cycle after 7-18 months of oral antiandrogen therapy. The effects of various regimens consisting of different doses of CPA in combination with ethinylestradiol (EE) were evaluated. The low-dose standard regimen (50 micrograms of EE plus 2 mg of CPA daily from day 5 to 25) caused regressive changes in the endometrium, i.e., sparse atrophic glands, relatively compact stroma, islands of stromal edema. These alterations correspond to those induced by conventional balanced low-dose combined oral contraceptives. High-dose reversed sequential regimen (40 micrograms of EE daily from day 5 to 25 plus 100 mg of CPA daily from day 5 to 14) resulted in pseudodeciduation and massive stromal edema. Pseudodeciduation during the early secretory phase is taken as a sign of the progestational depot effect of CPA, while the stromal edema is regarded as a result of the relatively unopposed estrogen intake during the second half of the treatment cycle. Thus, the effects of CPA containing drug on the endometrium depend essentially on their type, dosage and mode of administration.

Adult↗

A Sertoli-Leydig cell tumor and pregnancy. Clinical, endocrine, radiologic, and electron microscopic findings.

An extremely rare case of a conception occurring in a 26-year-old patient with a small virilizing Sertoli-Leydig cell tumor (diameter: 0.6 cm), bilateral polycystic ovaries and non-tumorous adrenal hyperandrogenism is presented. Prepregnancy findings included hirsutism, clitoromegaly, secondary amenorrhea, and elevated peripheral plasma testosterone (T; 5.7 ng/ml). Extensive basal steroid screening, dynamic function tests, conventional radiologic procedures, selective glandular vein catheterization, and laparoscopy failed to localize unequivocally the source of androgen excess, but suggested bilateral adrenal involvement. The patient conceived during the diagnostic work-up; peripheral T levels increased to 12.1 ng/ml within the first trimester. An exploratory laparotomy with left adrenalectomy, right adrenal biopsy and left ovarian wedge resection revealed an incompletely removed Sertoli-Leydig cell tumor, but normal adrenal histology. The pregnancy was terminated, a left oophorectomy and right ovarian wedge resection were performed at 14 weeks' gestation. Subsequently, peripheral androgens returned to normal, regular menses resumed, and hirsutism disappeared. Three years later the patient delivered a healthy female infant.

Abortion, Therapeutic↗