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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 127 records · Page 7Linked to original sources

Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men.

The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.

Adult↗

Nyctohemeral growth hormone profiles in young and aged men: correlation with somatomedin-C levels.

The effects of aging on GH secretion and somatomedin-C (SM-C) levels were studied in 10 young (22-45 yr) and 10 elderly (65-85 yr) men. Plasma GH levels were measured in samples obtained at 20-min intervals for 1300 min. Plasma SM-C levels were measured in samples obtained at 0600, 1100, 1600, 2100, and 0200 h. In the elderly men the mean basal plasma GH level was similar to that in the young men, but the total GH peak area as well as the amplitude of the peaks were significantly (p less than 0.01) lower than those in young men during both the day and the night. Plasma SM-C levels were significantly lower in the elderly men and were correlated with the total integrated GH levels and total GH peak areas, but not with basal plasma GH levels, suggesting that the GH peaks determine SM-C levels and that the decreased GH secretion in elderly men has biological significance.

Adult↗

The effect of maternal employment during preschool years on school readiness.

Many children referred because of 'learning disability' have mothers in full-time employment. This study was undertaken to examine the effect of maternal employment on school readiness. One hundred and seven children were studied. Forty-six were the offspring of women who had not gone out to work since the birth of the child (group A). The mothers of the other 61 had worked for 1 year or more during the lifetime of the child (group B). The mother of each child completed a detailed questionnaire. Each child was subjected to standardized tests of reasoning, numerical ability, Gestalt, verbal comprehension, eye-hand co-ordination, visual and auditory perception and IQ. Groups A and B were compared with regard to marital status of parents, their educational attainments, family size, ordinal position of the index child and years of nursery school experience. Educational attainments of both fathers and mothers were significantly higher in group A and children had spent significantly longer at nursery school. Group B (working mothers) had a predictably higher incidence of single parents. Comparison of results showed no significant difference between groups A and B for 6 of the 8 tests administered. Group B results did not differ significantly when divided into categories according to years of maternal employment. The study suggests that there is no direct relationship between maternal employment and maturity at school entry.

Aptitude Tests↗

Steroid dynamics in the normal and carcinomatous mammary gland.

UNLABELLED: As an approach to the study of the origin of estrogens in breast cancer tissue, the concentration of estrogens and their androgen precursors, as well as aromatase and 17 beta-dehydrogenase activities in normal glandular (GL) and cancerous (CA) breast tissue were determined and correlations with plasma levels and/or receptor status were studied. In both normal GL and CA breast tissue, steroid concentrations were significantly higher than plasma conc., except for dehydroepiandrosterone sulphate (DHEAS), estrone sulphate (E1S) and testosterone (T). Androgen conc. were lower, but estrogen conc. were higher in CA than in GL breast tissue. Estradiol (E2) conc. was positively correlated with the E2R conc., mean E2 conc. corresponding to an estimated E2R occupancy of about 25%. Aromatase and 17 beta-hydroxysteroid dehydrogenase (E2DH) (E2----E1) activities were observed in all breast CA and GL tissues, aromatase accounting probably only for a small fraction of tissue estrogens. E2DH, but not aromatase activity, was significantly higher in E2R+ than in E2R- tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and DHEAS conc.; the latter two steroids are non competitive inhibitors of E2DH which inactivates E2 to E1. CONCLUSION: in both normal and carcinomatous breast tissue, conc. of E1 and E2 are significantly higher than in plasma, suggesting either uptake or local synthesis. As to the latter, aromatase activity accounts probably only for a minor fraction of the tissue estrogens. Breast CA tissue has higher aromatase and E2DH activity than normal glandular tissue, E2 conc. and E2DH activity being higher in E2R+ hormone sensitive, tumors than in E2R-tumors. Tissue conc. of DHEA(S) which inhibits oxidative inactivation of E2, is negatively correlated with E2DH activity and may have an important modulating role in intratissular estrogen metabolism.

17-Hydroxysteroid Dehydrogenases↗

Intratesticular unconjugated steroids in elderly men.

As an extension of our studies on the influence of age on testicular function and with the aim of detecting whether the decline in testosterone production by aged testes is accompanied by a block in the biosynthetic chain leading from cholesterol to testosterone, we determined in the testis of young and elderly men, who died suddenly either from a cardiac incident or from accident, intratesticular steroids: pregnenolone, 17 hydroxypregnenolone (3 beta, 17 alpha-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone, androstenediol, (5-androsten-3 beta, 17 beta-diol), progesterone, 17 hydroxyprogesterone, androstenedione, 17 beta-estradiol as well as testosterone, dihydrotestosterone (5 alpha-androstan-17 beta-ol-3-one) and androstanediol (5 alpha androstane-3 alpha, 17 beta-diol). The intratesticular steroid pattern in elderly men was essentially characterized by a decrease of the 5-ene steroid concentration, whereas we did not observe a decrease in the 4-ene steroids, progesterone concentration being even significantly higher in the aged testes. There was no evidence for a decrease in either lyase or 17-hydroxylase activity. It is suggested that the steroid pattern as observed in the aged testes is the consequence of a decreased oxygen supply, due to a decreased testicular perfusion.

17-alpha-Hydroxypregnenolone↗

Aromatase, 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women.

In a study of the origin of estrogens in patients with breast cancer, the concentrations of estrogens and their androgen precursors, and aromatase and 17 beta-hydroxysteroid dehydrogenase (E2DH) activities were determined in normal glandular and cancerous breast tissue. The correlation between tissue estrogens, precursor concentrations, enzyme activities and plasma levels and/or receptor status were calculated. In both normal glandular and carcinomatous breast tissue, the concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), 5 androstene-3 beta, 17 beta-diol (5-Adiol), estrone (E1), estradiol (E2) and progesterone (P) were significantly higher than plasma concentrations. While testosterone (T) concentrations were similar, dehydroepiandrosterone (DHCA) and estrone sulphate (E1S) concentrations were lower in tissue than in plasma. In carcinomatous tissue androgen concentrations were lower, but estrogen concentrations were higher than in glandular breast tissue. Estradiol (E2) concentration was positively correlated with the receptor concentration with the mean E2 concentration corresponding to an estimated receptor occupancy of about 25%, probably sufficient for a submaximal biological response. Aromatase and E2DH (E2----E1) activities were observed in all breast cancer and glandular breast tissues, activities being higher in carcinoma than in glandular breast tissues; nevertheless, aromatase activity accounts probably only for a small fraction of tissue estrogen concentration. E2DH, but not aromatase activity, was significantly higher in estrogen receptor positive than in estrogen receptor negative tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) concentration; the latter two steroids are non competitive inhibitors of E2DH which inactivates E2 to E1. This effect of DHEA(S) may constitute a mechanism by which these androgens stimulate cancer growth and a rationale (besides suppression of estrogen precursors) for medical or surgical adrenalectomy in hormone sensitive metastatic mammary cancer. E2DH activity might constitute an additional marker of hormone dependency of mammary cancer.

17-Hydroxysteroid Dehydrogenases↗

Alternating chemotherapy, prophylactic cranial irradiation and late local thoracic irradiation for small-cell lung cancer.

28 consecutive patients with small-cell lung cancer (SCLC) aged 48-78 years (with exclusion of 4 patients over 80 years) were treated with combination chemotherapy in the schedule AAA-BBB-AAA-BBB, where A consisted of cyclophosphamide 1,000 mg/m2, adriamycin 50 mg/m2, and etoposide 100 mg/m2 X 3, and B of cyclophosphamide 1,000 mg/m2, methotrexate 50 mg/m2 and vincristine 1 mg/m2 X 2. Patients in complete remission after 3 courses received prophylactic cranial irradiation, and thoracic irradiation was given after completion of chemotherapy. There were 3 toxic deaths. Of the patients with limited disease, 71% reached complete remission and 24% partial remission; in extensive disease these percentages were 36 and 45%, respectively. Three patients survived more than 2 years, 1 with recurrence of squamous cell carcinoma after 125 weeks. It is concluded that this scheme of combination chemotherapy is as effective as those reported earlier in remission rate and survival in SCLC. However, the addition of thoracic irradiation failed to prevent local relapse in 83% of the patients.

Aged↗

Human mammary cancer as a site of sex steroid metabolism.

Oestrogen-progesterone imbalance in favour of the oestrogens is considered to be an important factor in the development of mammary cancer, although oestrogens are not directly mitogenic. Moreover, this promoter effect of carcinogenesis may be limited in time. Except for increased plasma (free) oestradiol levels, plasma sex hormone levels in breast cancer patients are comparable to those in normal women, matched for age and weight. In both benign and malignant breast tissue, sex hormone concentrations (ng/g) are significantly higher than in plasma (ng/mg), except for dehydroepiandrosterone sulphate, oestrone sulphate and testosterone, but in breast cancer tissues, dehydroepiandrosterone sulphate (DHEAS), 5 alpha-androstane-3 alpha-17 beta-diol and progesterone concentrations are lower than in normal breast tissue. As to the origin of these sex hormones in breast tissue, a positive arteriovenous gradient across the breast tissue has been observed for androstenedione and oestradiol, suggesting uptake from plasma by the tissues. Aromatization of androstenedione, on the other hand, is probably only a minor source of oestrogens in breast tissue. Hydrolysis of oestrone sulphate taken up from the blood, or oestradiol-17 beta fatty acid esters may be another source, but data are too scarce at present to draw a final conclusion as to their role as source of tissue oestrogens. 17 beta-hydroxysteroid dehydrogenase activity, inactivating oestradiol into oestrone, may be an important determinant of tissue oestradiol concentration. This enzyme activity was found to be higher in oestrogen receptor positive than in oestrogen receptor negative tissues and was negatively correlated with DHEA and DHEAS concentrations. As it was shown that the latter two steroids are non-competitive inhibitors of the 17 beta-hydroxysteroid dehydrogenase as well as of the oestrogen-sulphotransferase, it appears that DHEA may be an important modulator of tissue oestradiol concentration, whereas the 17 beta-hydroxysteroid dehydrogenase might constitute an additional marker of hormone dependency of breast cancer.

Breast Neoplasms↗

Osteonecrosis of sternum and rib in a patient treated for Hodgkin's disease.

A 39-year-old man is described in whom osteonecrosis of the manubrium sterni developed 23 months and of a rib 25 months after treatment for Hodgkin's disease Stage IIIB with polychemotherapy and subdiaphragmatic radiotherapy. The radiologic and histologic characteristics of this very rare localization of steroid-associated osteonecrosis are discussed.

Adult↗

Chromosome-sized DNA molecules of Plasmodium falciparum.

At least seven chromosome-sized DNA molecules (750 to 2000 kilobases in length and one fraction of undetermined molecular weight) from cultured clones and isolates of Plasmodium falciparum have been separated by pulsed-field gradient gel electrophoresis. Whereas asexual blood stages and sexual stages of the same line have identical molecular karyotypes, the length of chromosome-sized DNA molecules among different geographical isolates and several clones derived from a single patient is different. These length alterations of chromosomes are the result of DNA rearrangements that must occur unrelated to sexual differentiation.

Animals↗

Effect of long-term hormonal contraception on plasma lipids.

Serum lipid and apoprotein levels were determined in fasting women after long-term use (5-12 years) of Depo Provera, Orgametril, Ortho Novum SQ, Binordiol, Microgynon-50, and Ministat. Compared with matched controls, pure progestogens (Depo Provera and Orgametril) caused a moderate decrease of TG, HDL chol, and Apo A1, whereas estrogen-dominant oral contraceptives (Ortho Novum SQ) increased the same parameters. The effects of long-term use of hormonal contraception on lipids did not differ from those predicted from short-term (6 months) studies.

Adult↗

Testicular endocrine function in the ageing male.

The decrease of plasma testosterone (T) in elderly men may be inherent to the ageing process or secondary to environmental factors such as stress, smoking and physical activity. Plasma T, apparent free T and gonadotropin levels were determined in healthy men aged 26-90 yr living under identical conditions (as monks in a monastery). We found a highly significant age-dependent decrease in T and apparent free T levels, and an increase in gonadotropin levels. The nyctohemeral variation in T levels was lower in elderly than in younger males. When studied in a larger group, smokers had higher T levels than non-smokers, whereas in young men plasma T levels were more sensitive to stress than in elderly men. Neither moderate physical activity, diet nor residence consistently altered plasma T levels. We conclude that the age-associated decrease in plasma T levels is inherent to the ageing process and that the major cause is at the testicular level, although there is evidence for subtle alterations at the hypothalamo-pituitary level.

Adult↗

Long-term transdermal dihydrotestosterone therapy: effects on pituitary gonadal axis and plasma lipoproteins.

In order to investigate whether dihydrotestosterone (DHT) alone has an inhibiting effect on pituitary luteinizing hormone (LH) secretion, and whether this natural androgen has any effect on plasma lipids when administered transdermally, dihydrotestosterone was applied for 3 mth in a daily dose of 125 or 250 mg in gel form for transdermal absorption (Andractim) to elderly males with relatively low plasma testosterone levels. The results clearly show that DHT inhibits LH secretion, as plasma LH levels were decreased, although testosterone, free testosterone, estradiol and free estradiol levels were decreased. Regarding plasma lipid levels, DHT administration for 3 mth resulted in a moderate decrease in plasma cholesterol and low-density lipoprotein (LDL) levels, and a slight decrease in high-density lipoprotein (HDL)-cholesterol levels, the HDL/TLC ratio remaining constant. This suggests that percutaneous DHT administration is a relatively safe modality of androgen replacement therapy as far as atherogenicity is concerned.

Administration, Topical↗

Double-blind comparison of prenylamine and penbutolol in patients with angina pectoris.

This study was performed to re-evaluate the clinical position of prenylamine in the management of angina pectoris. After 1 week withdrawal of all anti-anginal agents, followed by another week of placebo administration, seventeen patients were allocated at random to 6 weeks treatment with either penbutolol 40 mg once a day or prenylamine 60 mg t.i.d. Clinical examination, exercise test and anginal attack rate were recorded every 2 weeks. Both drugs reduced the anginal attack rate. None of the drugs caused a significant increase in maximal workload or a significant change in ST-segment depression. Beside a substantially lower rate-pressure product at maximal comparable workload in the penbutolol group (p less than 0.001), no significant differences were observed between the two drugs. No adverse reactions were reported. From these results one can conclude that prenylamine and penbutolol do not differ in their anti-anginal effect. Therefore we are of the opinion that prenylamine has a place in the therapeutic armamentarium for the management of angina pectoris, particularly in patients where beta-blocking agents are contraindicated or in patients who have experienced side-effects of beta-blocking or calcium-entry blocking agents.

Aged↗