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Biomedical subjects

R Stege

Publications and source records attributed to R Stege.

At least 37 records · Page 2Linked to original sources

Neoadjuvant GnRH-agonist treatment (triptorelin and cyproterone acetate for flare protection) and total prostatectomy.

The effects of 3 months treatment with the GnRH agonist triptorelin as a neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by digital rectal examination, transrectal ultrasound before and after treatment. Serum testosterone and prostate-specific antigen (PSA) levels were followed. The totally removed prostate gland was step-sectioned at 5-mm intervals and the whole-mount sections were assessed for tumour pathology stage (pT stage). Triptorelin treatment resulted in a significant decrease in total gland and tumour volume and in a reduction in the serum levels of PSA and testosterone. In comparison with the findings from a previous study, in which neoadjuvant treatment was not used, it appears that the proportion of tumours invading the margins of the surgical specimen decreased.

Adenocarcinoma↗

[A study on prostatic cancer. The patient can decide himself: medical or surgical treatment].

In a multicentre study, 101 consecutive patients with advanced prostate cancer were offered the choice of orchiectomy or treatment with an LHRH analogue. Together with the cancer diagnosis the patients were given verbal information about the treatment alternatives, and detailed written information to peruse at home. One week later the patients informed the attending physicians of their choice. Information as to the reasons for the patients' choice, and their views on their choice after the start of treatment were elicited by questionnaire. Of the 101 patients, 48 chose orchiectomy, and 48 treatment with an LHRH analogue, five patients being excluded owing to their inability to decide. Mean age was about 73 years in both treatment groups, and about two thirds of each group lived with a partner. The level of education was higher among those who chose medical treatment. The predominant reasons for the choice of treatment were as follows: Orchiectomy, simpler (31 per cent), troublesome having to have monthly injections (19 per cent), simple to perform (15 per cent); medical treatment, possibility of change in treatment (27 per cent), simpler (17 per cent), fear of surgery (15 per cent). Most patients in both groups had no difficulty deciding, chose quickly, felt sure about their choice, appreciated the opportunity of choosing, and had discussed their choice with their partners or intimates. Three months after the start of treatment, almost all patients were still satisfied with their choice, and had no wish to change their choice even if that were possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Testicular and adrenocortical function in healthy men and in men with benign prostatic hyperplasia.

The influence of aging upon serum concentrations of testicular steroids, sex hormone binding globulin (SHBG) and pituitary hormones and on adrenal steroid levels and adrenal steroid response to ACTH was studied in 81 healthy men aged 20-87 years. These endocrine variables were also compared in 43 patients with benign prostatic hyperplasia (BPH), aged 58-89 years and in a subgroup of 41 men, aged 58-87 years, from the above mentioned reference population. The normal endocrine aging was characterized by a rise in SHBG levels, decreasing levels of testicular steroids and non-SHBG-bound testosterone (NST) and increasing gonadotropin levels and decreasing concentrations of total estrone. Adrenal androgen levels decreased in the presence of unchanged levels of cortisol and the adrenal steroid response to ACTH changed by decreasing increments in dehydroepiandrosterone (DHA) and increasing increments in 17 alpha-hydroxyprogesterone (17OHP). With the exception of the alterations in SHBG and adrenal androgens, all these changes were finished before the seventh decade of life. BPH patients had elevated levels of testosterone and NST in the presence of normal SHBG and gonadotropin levels, elevated levels of DHA and DHA sulfate (DHAS) in the presence of normal cortisol levels, a "younger" pattern of adrenal steroid response to ACTH as judged from the increments in DHA and 17OHP, elevated ratios between estrone and 4-androstene-3,17-dione suggesting an increased peripheral aromatization and subnormal prolactin levels. BPH patients may be considered as "endocrinologically younger" than healthy subjects. DHA and especially its proximate metabolite 5-androstene-3 beta, 17 beta-diol exert powerful estrogenic effects on the receptor level. Thus the elevated levels of DHA and DHAS in the BPH patients may create an hyperestrogenic condition in addition to the slight hyperandrogenicity caused by the elevated NST levels. Both endocrine aberrations may play a role in the etiology of BPH, in accordance with the dual sex steroid sensitivity of the periurethral glands.

Adrenal Cortex↗

Quantitative estimation of tissue prostate specific antigen, deoxyribonucleic acid ploidy and cytological grade in fine needle aspiration biopsies for prognosis of hormonally treated prostatic carcinoma.

The prognostic value of deoxyribonucleic acid (DNA) flow cytometry, cytological grading and the direct assay of prostate specific antigen (PSA) in the material of fine needle aspirates was studied in 67 consecutive patients with newly detected prostatic carcinoma. All patients were hormonally treated (castration in 27 and luteinizing hormone-releasing hormone agonist or parenteral estrogens in 40). The patients were followed for a minimum of 2 years. PSA was analyzed in the biopsy material by a direct radioimmunoassay and related to the total amount of DNA. In parallel biopsies DNA ploidy using flow cytometry and cytological grade were established. Patients with a geometric mean value of greater than or equal to 0.12 microgram. PSA/microgram. DNA had a progression rate of 7%, compared to 59% for those with less than 0.12 microgram. PSA/microgram. DNA. In Cox multivariate analysis cytology and tissue PSA content were the most important factors in expressing the difference for interval to progression in hormonally treated patients.

Antigens, Neoplasm↗

Effects of orchidectomy and different modes of high dose estrogen treatment on circulating "free" and total 1,25-dihydroxyvitamin D in patients with prostatic cancer.

Serum levels of total 1,25-dihydroxyvitamin D (1,25(OH)2D), vitamin D binding protein (DBP), sex hormone binding globulin (SHBG), testosterone, estradiol 17 beta (E2) and the "free" 1,25(OH)2D index were measured before and during treatment in prostatic cancer patients treated by orchidectomy (n = 15), with combined i.m. polyestradiol phosphate (PEP) + oral ethinyl estradiol (EE) (n = 10) and with i.m. PEP only for 3 months, followed by addition of oral EE (n = 9). Total concentrations of 1,25(OH)2D and DBP were unaffected by orchidectomy and treatment with i.m. PEP only, but were significantly elevated during treatment including oral EE. SHBG levels were unaffected by orchidectomy, slightly increased by i.m. PEP only and greatly increased by oral EE. The free 1,25(OH)2D index was slightly elevated by treatment including oral EE. Evidence was obtained that the increase in 1,25(OH)2D levels observed during oral estrogen treatment was secondary to the estrogen-augmented increase in DBP and not a result of an estrogen-stimulated synthesis of 1,25(OH)2D. Furthermore, the stimulatory effect of estrogen on DBP concentrations seemed to be dependent on the route of administration of the hormone.

Aged↗

Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer.

The present study compares the cost of antitumor therapy and adverse cardiovascular effects during the first year of treatment with oral estrogens, nonoral estrogens, or surgical castration in patients with prostatic cancer. We found a much higher cost for patients treated with orchidectomy and oral estrogens than for patients treated with nonoral estrogens. Twenty-five percent of the patients treated with oral estrogen suffered cardiovascular complications, compared to none of the patients treated by orchidectomy or nonoral estrogens. The initial cost of orchidectomy as compared to nonoral estrogen treatment was shown not be balanced within the expected survival time of patients with advanced prostatic cancer. Furthermore, surgical castration causes psychological trauma to the patient. We recommend parenteral estrogen therapy as a low-cost therapeutic regimen in patients with prostatic cancer.

Administration, Oral↗

Flutamide has no effect on adrenal androgen response to acute ACTH stimulation in patients with prostatic cancer.

Basal levels and adrenocorticotropic hormone (ACTH)-induced increments (delta-values) of serum cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), 4-androstene-3, 17-dione (A4), and 17-hydroxyprogesterone (170HP); basal testosterone (T), luteinizing hormone (LH), serum ASAT, gamma-GT, and albumin were measured in prostatic cancer patients before and after 6 months of treatment with LH-RH-agonist, with flutamide, and with LH-RH-agonist + flutamide, respectively. Basal DHA and DHAS were decreased during flutamide and LH-RH-agonist + flutamide treatment and basal A4 during treatment with LH-RH-agonist and with LH-RH-agonist + flutamide. Basal 170HP, T, and LH decreased during LH-RH-agonist and LH-RH-agonist + flutamide treatment and increased during single drug flutamide treatment. Slightly decreased delta cortisol values were observed during LH-RH-agonist and during flutamide treatment and slightly increased delta 170HP values during LH-RH-agonist and LH-RH-agonist + flutamide treatment. Values for delta DHA and delta A4 were completely unaffected by any of the treatment regimens. Elevated ASAT values were observed during treatment with flutamide and with LH-RH-agonist + flutamide. It is concluded that flutamide has no effect on the adrenal androgen response to acute ACTH stimulation.

Adrenocorticotropic Hormone↗

Deoxyribonucleic acid ploidy and the direct assay of prostatic acid phosphatase and prostate specific antigen in fine needle aspiration biopsies as diagnostic methods in prostatic carcinoma.

We used fine needle biopsies from prostatic tumors at routine examinations in 133 patients. Cytological grading was performed with a scoring system. Cellular prostatic acid phosphatase and cellular prostate specific antigen from the aspirates were quantitated. Deoxyribonucleic acid flow cytometry was performed and the tumors were subdivided into diploid, tetraploid and aneuploid groups. Tumor staging was assessed by digital examination. A decrease in the biochemical markers was significantly correlated with the increase in malignancy grade, tumor stage and a shift from diploid to aneuploid tumors. Cellular prostatic acid phosphatase and cellular prostate specific antigen as well as tumor ploidy may contribute to the objective determination of the malignancy potential of the prostatic carcinoma.

Acid Phosphatase↗

Relationship between serum testosterone and sex hormone-binding globulin in adult men with intact or absent gonadal function.

Serum levels of testosterone and sex hormone-binding globulin (SHBG) were determined in 80 apparently healthy men aged 25-85 years and in 23 patients with prostatic carcinoma (CAP) aged 60-75 years before and 6 months after orchidectomy. Serum levels of testosterone and SHBG were correlated positively in healthy men, in all subjects overall as well as within different age groups, and in CAP patients before, but not after, orchidectomy. These data are not consistent with the classical theory regarding SHBG regulation and also speak against an influence of SHBG binding on testosterone metabolism as a mechanism behind the observed positive association between testosterone levels and SHBG.

Adult↗

Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma.

Patients with prostatic carcinoma on oral oestrogen therapy have an altered coagulation system and suffer cardiovascular side effects. Oestrogens--especially oral oestrogens--are potent inducers of liver synthesised proteins, including coagulation factors. We have assessed the effect of non-oral oestrogen on the coagulation system in patients with prostatic carcinoma. Twelve patients were given monthly intramuscular injections of 320 mg polyoestradiol phosphate (PEP). No additional oestrogens were given. No change was found in any of the coagulation factors, including factor VII, with the exception of a significant decrease in antithrombin III. No patient, including 38 patients treated with PEP, had any cardiovascular complications after a mean follow-up period of 12.9 +/- 0.7 months; 76% of the patients responded to treatment. Parenteral administration of oestrogen caused a less marked change in the coagulation system than oral administration and should be the treatment of choice for prostatic carcinoma.

Antithrombin III↗

Adrenocortical function in prostatic cancer patients: effects of orchidectomy or different modes of estrogen treatment on basal steroid levels and on the response to exogenous adrenocorticotropic hormone.

Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP. Orchidectomy caused a slight decrease in basal DHAS, while combined oral + intramuscular estrogens caused a pronounced decrease in basal DHAS and also in DHA. Single drug intramuscular estrogens did not affect basal DHA or DHAS levels. Increased basal cortisol levels appeared during combined oral + intramuscular estrogen therapy. delta DHA and delta A-4 values were unaffected by endocrine treatment, but delta 17-OHP and delta cortisol increased slightly after orchidectomy and during estrogen therapy. Significantly decreased albumin levels were only observed during combined oral + intramuscular estrogen treatment. Determination of estriol, which is a major metabolite of estradiol originating from polyestradiol phosphate, revealed significantly higher estriol levels during combined oral + intramuscular estrogen treatment than during single drug intramuscular estrogen therapy, indicating an increased induction of hepatic 16 alpha-hydroxylase activity. The pronounced decreases in DHAS and also in DHA during combined oral + intramuscular estrogen treatment are probably another reflexion of the liver side effects of oral estrogens.

17-alpha-Hydroxyprogesterone↗

Serum hormone levels in men with end stage renal disease.

Serum concentrations of testicular and adrenal androgens and androgen precursors, cortisol, unconjugated (E1) and total estrone (tE1; greater than or equal to 85% E1 sulfate), pituitary hormones, sex hormone binding globulin (SHBG) and albumin were measured in 14 male patients with non-diabetic end stage renal disease and in 28 age-matched healthy controls. The serum levels of the adrenal androgens 4-androstene 3,17-dione and dehydroepiandrosterone (DHA) were significantly lower and the levels of cortisol, LH, prolactin and tE1 significantly higher in the patients than in the controls. The ratios between E1 and tE1 and between DHA and DHA sulfate were strongly decreased in the patients. The findings are suggested to reflect different effects of the disease upon the metabolism of cortisol and of adrenal androgens and also the reduced or even absent urinary excretion, leading to a decreased metabolism of steroid conjugates.

Adult↗

Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate.

To study the influence of tumour mass on lipid metabolism, the lipoprotein pattern in untreated patients with newly diagnosed cancer of the prostate was examined. Total cholesterol levels were reduced in patients with evidence of metastasis (n = 30) compared with those without metastasis (n = 73). Since the major fraction of serum cholesterol is contained in low-density lipoproteins (LDL), turnover of LDL was studied in detail in 8 patients compared with 12 age-matched healthy men. LDL were cleared faster in the 3 patients with metastatic disease than in the patients without metastasis and in controls, indicating faster catabolism of LDL. Thus in prostatic cancer an increased tumour burden is associated with increased elimination of LDL, which contributes to reduced serum cholesterol levels.

Aged↗

PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: relation to hormone sensitivity and to cytological grading.

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.

Acid Phosphatase↗

A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy.

The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.

Administration, Oral↗

Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens.

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.

Aged↗

Estrogen therapy and liver function--metabolic effects of oral and parenteral administration.

Oral estrogen therapy for prostatic cancer is clinically effective but also accompanied by severe cardiovascular side effects. Hypertension, venous thromboembolism, and other cardiovascular disorders are associated with alterations in liver metabolism. The impact of exogenous estrogens on the liver is dependent on the route of administration and the type and dose of estrogen. Oral administration of synthetic estrogens has profound effects on liver-derived plasma proteins, coagulation factors, lipoproteins, and triglycerides, whereas parenteral administration of native estradiol has very little influence on these aspects of liver function.

Administration, Oral↗