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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 109 records · Page 6Linked to original sources
PubMed1989

A new look to the andropause: altered function of the gonadotrophs.

After being controversial for a long time, the age associated decline in plasma T levels and secretion in normal men is now generally accepted. Although most data point towards a primary testicular origin for the decline in Leydig cell function, other data point towards alterations at the hypothalamo-pituitary levels: T levels in elderly men are decreased notwithstanding an important secretory reserve of both LC and gonadotrophs. Nycthemeral variations in plasma T levels are significantly decreased in elderly men. The increase in immunoreactive LH levels is dysproportionate to the increase of bioactive LH levels. Study of the activity of the LHRH pulse generator in 27 young and 21 elderly men revealed a significant decrease in frequency of high amplitude pulses for both LH and T. Moreover the sensitivity of the gonadostat to sex hormone feed back was significantly greater in the elderly men. Acute administration of an antiopoid (Naloxone), 2 mg i.v. both in young and elderly men at rest showed that in young and elderly men, Naloxone induced a comparable increase of LH levels. Naltrexone on the other hand increased LH pulse frequency in elderly but not in young men. The data show that opioids maintain their inhibitory effect on LHRH secretion in elderly men and suggest either that the opioid tone in the elderly men is decreased or that the response of the gonadotrophs to LHRH is decreased.

Adult↗
PubMed1989

Precursors of plasma androstanediol- and androgen-glucuronides in women.

Although androstanediol (AD) and androstanediolglucuronide (ADG) are generally considered to be parameters of peripheral androgen action, their plasma levels do not always vary in parallel, suggesting that they may have different precursors. Few hard data being available concerning ADG precursors in women, we studied in postmenopausal women with absent or suppressed adrenal function, the blood conversion rates of testosterone (T), dihydrotestosterone (DHT), androstenedione (A) and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) to AD and ADG respectively, as well as the conversion of AD to ADG. Moreover conversions of these precursors to testosteroneglucuronide (TG) and dihydrotestosteroneglucuronide (DHTG), respectively, were also studied. Our data show that, whereas plasma A and DHT are the major precursors of AD, plasma DHEAS and A are the major precursors of plasma ADG, accounting for 50 and 15%, respectively, of plasma ADG, A being the major precursor of plasma TG and DHTG, respectively. When the conversion rates, obtained in this study, were applied to the plasma concentration of precursors found in normal young and postmenopausal women, respectively, the calculated concentration of product steroids accounted for almost the totality of the actual plasma levels of ADG, TG and DHTG respectively. The difference in relative importance of their precursors, explains that plasma concentrations of AD and ADG do not always vary in parallel; moreover, the importance of DHEAS as precursor of ADG explains the suppression by dexamethasone and the increase after adrenocortical stimulation of plasma ADG levels.

Adult↗
PubMed1989

Persistence of increased bone resorption and possible role of dehydroepiandrosterone as a bone metabolism determinant in osteoporotic women in late post-menopause.

Specific data on bone metabolism in the late post-menopause are relatively scarce. This study presents data on the biochemical, hormonal and bone mineral status of a selected group of 22 osteoporotic women with at least 1 vertebral fracture who had been post-menopausal for a minimum of 5 yr. Bone resorption parameters were elevated in over two-thirds of these patients. The serum levels of dehydroepiandrosterone and its sulphate were negatively correlated with age and years since menopause but positively correlated with bone mineral content, bone turnover parameters (urinary calcium/creatinine, osteocalcin), 1,25-dihydroxy-vitamin D levels and the 1,25-dihydroxy-vitamin D/25-hydroxy-vitamin D ratio. These findings indicate that careful evaluation of the bone turnover rate in the late post-menopause can still have an important bearing on therapeutic decisions. They also support the theory that adrenal androgens play a role in bone mineral metabolism in the late post-menopause.

Age Factors↗
PubMed1989

MRI signal intensity profiles of sellar and perisellar lesions.

Literature data are reviewed and cumulated with our own findings in order to delineate the ability of MRI to evaluate the nature of sellar and perisellar lesions by analyzing their signal intensity profiles. The existence of different trends in T1 and T2 relaxation characteristics was documented within a spectrum of frequently presenting lesions. Magnetic resonance imaging (MRI) signal intensity analysis may contribute to exclude differential diagnostic problems remaining after computer tomographic examination of the sella. MRI should be the primary imaging test (in the absence of the known contra-indications) whenever a suspected pituitary or perisellar lesion has to be studied non-invasively.

Adenoma↗
PubMed1989

Plasma androstanediol glucuronide levels during pregnancy.

In distinction to Braunstein and Horton (1985) who reported an increase in maternal 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (ADG) plasma levels during pregnancy, we observed a decrease of these levels from the 10th week of pregnancy; the decrease parallels the decrease in dehydroepiandrosterone sulphate (DHEA-S) concentration. As the latter is a major precursor of ADG, the decrease in ADG levels during pregnancy is not unexpected and in line with the concept that ADG is a parameter of androgenicity.

Androstane-3,17-diol↗
PubMed1989

Lack of effect of the alpha-adrenergic agonist clonidine on pulsatile luteinizing hormone secretion in a double blind study in men.

This study was designed to evaluate the effects of alpha-adrenergic stimulation on the hypothalamic LHRH pulse generator in men. In 10 normal men, venous blood was sampled on 2 occasions at 10-min intervals for 8 h, beginning 30 min after oral administration of either placebo or 0.3 mg clonidine according to a randomized double blind protocol. Compared to placebo, clonidine induced a marked release of GH (P less than 0.0001 for response areas under the curve after placebo and clonidine), a fall in systolic and diastolic blood pressure and in heart rate (P less than 0.002 for areas under the curve after placebo and clonidine), and feelings of sedation and dry mouth (P less than 0.002 and P less than 0.05 for areas under the cumulative scores for changes in alertness and salivation, respectively). There was no difference between the results obtained after placebo and clonidine for the mean number of LH pulses [3.3 +/- 0.4 (+/- SE) and 3.3 +/- 0.3 pulses/8 h], for the mean amplitude of all LH pulses (3.8 +/- 0.4 and 4.1 +/- 0.5 IU/L), or for the areas under the LH concentration-time curve (2741 +/- 251 and 2728 +/- 215 IU/L.min). The lack of effect of clonidine on LH secretion at a dose that effectively induced GH secretion and other centrally mediated effects indicates that the actions of testosterone and opiates to decelerate the frequency of the LHRH pulse generator in men are not mediated by diminished alpha-adrenergic stimulation. From these results, taken together with previous data, we conclude that alpha-adrenergic systems do not play a major role in the regulation of episodic LH release in men.

Adult↗
PubMed1989

Influence of antiopioids on luteinizing hormone pulsatility in aging men.

To investigate whether changes in opioid tone play a role in the age-associated changes in LH release in men, the influence of an antiopioid, naltrexone, on plasma LH levels and LH pulses was studied in a group of young and elderly normal men. The young and elderly men had similar basal LH pulse frequencies, but the frequency of high amplitude (greater than 2 IU/L) LH pulses, mean LH pulse amplitude, maximal LH pulse amplitude and pulse area, were lower in the elderly men. Naltrexone administration (40 mg at 0630 and 2200 h the day before blood sampling and at 0630 h, 30 min before starting frequent blood sampling at 10-min intervals for 12 h) to young men (n = 8) induced a significant increase in individual mean baseline plasma LH levels, LH pulse frequency, and the sum of LH pulse amplitudes. In elderly men (n = 11) only a borderline significant increase in baseline plasma LH levels occurred, and neither LH pulse frequency nor the sum of the amplitudes of LH pulses increased. We suggest that in elderly men either opioid tone or the response of the gonadotrophs to endogenous LHRH is decreased.

Adult↗
PubMed1989

Effects of epanolol and metoprolol on the heart measured by 24-hour holter monitoring.

Continuous 24-hour ECG monitoring was performed as an additional objective in 87 patients from 5 centres in the VISA 1 study. The aim of the study was to compare the continuous 24-hour ECG recordings before the study and during treatment with epanolol ('Visacor') or metoprolol. Parameters of particular interest were heart rate and premature ventricular contractions (PVCs). Using the Oxford 4000 system with a 5-lead recorder, 24-hour monitoring was carried out on entry to the study (no antianginal therapy was allowed, with the exception of short acting nitrates), and at the end of both treatment periods. Measurements included the total number of heart beats and PVCs and the incidence of bradycardia. 87 patients, of mean age 59 (range 32 to 80) years, were included in the study. 62 patients had evaluable tapes available on both active treatment periods. The mean heart rate during 24 hours was significantly lower with metoprolol compared with epanolol treatment (64 vs 72 beats/min, respectively, p less than 0.001). The total number of PVCs in 24 hours was similar in both treatment groups and not significantly different from the value recorded at entry. The median total duration of bradycardia (heart rate less than 60 beats/min) in 24 hours was significantly (p less than 0.001) less for epanolol (60 minutes) than metoprolol (428 minutes). Plots of the mean hourly heart rates show that during daytime, epanolol was associated with a mean heart rate in between the rate observed without treatment and with metoprolol treatment. At night-time, almost identical values were found in the groups treated with epanolol compared with the non-treatment period, whereas the metoprolol treatment induced significant lower heart rate levels. Thus, it was shown that there was greater heart rate reduction with metoprolol than with epanolol (p less than 0.001), and that there was no heart rate reduction at night with epanolol. No arrhythmogenic effect was seen for either drug.

Adrenergic beta-Antagonists↗
PubMed1989

Bone reaction to silicone metatarsophalangeal joint-1 hemiprosthesis.

The incidence of inflammatory response to silicone implants in the first metatarsophalangeal joint was investigated. In 34 of 59 silicone arthroplasties, cysts were noticed in the proximal phalanx after a mean follow-up period of 59 months. In the metatarsal head, cysts were seen in 40 cases. Histologic examination showed that the cysts were filled with an avascular cellular stroma containing histiocytes and multinucleated giant cells, opsonizing wear debris of the prosthesis. Because of this destructive process, caution is advised when using silicone prostheses in young, active people.

Adolescent↗
PubMed1988

Effects of cyproterone acetate plus ethinylestradiol low dose on plasma androgens and lipids in mildly hirsute or acneic young women.

The purpose of this study was to compare, by a randomized double-blind study, involving 30 women with either acne or mild hirsutism, the effects on plasma androgens and lipoproteins, of two hormonal preparations used in acne and ensuring reliable contraception, namely DianeR (cyproterone acetate 2 mg and ethinylestradiol 50 micrograms per pill - D-50) and Diane 35 (cyproterone acetate 2 mg and ethinylestradiol 35 micrograms per pill - D-35). Both drugs, used over a 6-month period (treatment cycle of 21 days with a pill-free interval of 7 days), induced an impressive decrease of free testosterone levels and of 5 alpha-androstane-3 alpha, 17 beta-diol-glucuronide, a parameter of peripheral androgen formation; also dehydroepiandrosterone sulfate levels decreased significantly. Except for an increase of both total T and dihydrotestosterone and as well as for a more important increase in SHBG levels during treatment with D-50, consequences of its more pronounced estrogen dominance in comparison to D-35, the effects of both drugs on androgen levels were similar. The effects on lipids were characterized by a non-significant increase of total cholesterol and a significant increase of HDL-C, HDL2-C and Apo-Al lipoproteins, which were somewhat more pronounced during D-50 treatment. Triglycerides increased significantly during D-50 but hardly during D-35 treatment, whereas HDL-C/LDL-C increased similarly during treatment with either drug. It is concluded that, being as efficient as D-50 in treatment of acne and hirsutism and taking into account its reliable contraceptive effects, without unfavourable effects, as far as atherogenesis is concerned, on plasma lipids, D-35 is to be preferred over D-50.

Acne Vulgaris↗
PubMed1988

Flow cytometric analysis of DNA ploidy level in paraffin-embedded tissue of non-small-cell lung cancer.

Investigations regarding the prognostic value of DNA content (ploidy) and proliferative characteristics [percentage of cells in S-phase or S-phase fraction (SPF)] have been greatly facilitated by the application of flow cytometry (FCM) using nuclei isolated from paraffin-embedded tissue. We have applied this technique to tumor sections from patients presenting with non-small-cell lung cancer (NSCLC) in 1980 and 1981. From 67 out of 115 patients material of sufficient quantity and quality was obtained to perform DNA-FCM. A multivariate analysis including stage of disease (UICC), age, tumor histology and treatment modality was performed to examine the prognostic significance of DNA-FCM in NSCLC. Aneuploidy was found in 65% of cases. In our study, the DNA content was not related to histology, stage of disease or treatment modality, nor to the length of survival (log rank test P = 0.62). Calculation of SPF was possible in 49/67 cases. The SPF was not related to histology, stage of disease or treatment modality, but a significant prognostic value was found for survival; patients with a high SPF died earlier (P = 0.04) and this was especially true for squamous cell carcinoma (P = 0.02). This study demonstrates the prognostic importance of DNA-FCM-derived information in NSCLC using a multivariate analysis; however further prospective studies in larger patient populations are needed.

Adenocarcinoma↗
PubMed1988

Ventricular ectopic activity during exercise testing in patients with myocardial infarction. The relation to severity of coronary artery disease and return to work.

Ninety-eight male patients with a first myocardial infarction aged 40-55 years were randomly assigned to either a control group or to a six-week intensive cardiac rehabilitation programme. An exercise test was performed at 8 to 16 weeks after myocardial infarction and thereafter every year for five years. Ventricular ectopic activity during exercise testing had no influence on return to work in the first year, although it was related to the development of angina pectoris. Angina pectoris was the only discriminating factor for return to work and in this group of patients cardiac rehabilitation did not show any influence. Possible reasons for this lack of effect are discussed.

Arrhythmias, Cardiac↗
PubMed1988

Leydig cell function in infertile men with idiopathic oligospermic infertility.

To evaluate Leydig cell function in men with idiopathic oligospermic infertility and its eventual role in their infertility, plasma LH, testosterone (T), 17-hydroxyprogesterone (170HP), and estradiol levels as well as plasma T/LH and 170HP/T ratios were measured in 103 such men, subdivided into different groups according to their plasma FSH levels. The results were compared to results in normal young fertile men, the subgroup of men with idiopathic oligospermic infertility who within 12 months after consultation succeeded in impregnating their partner, infertile men with a history of undescended testes (excryptorchid men), and men with Klinefelter's syndrome. As a tentative parameter of androgen insensitivity, an androgen insensitivity index [LH (IU/L) X T (nMol/L)] was calculated. Although all men with idiopathic infertility had plasma T and LH levels within the normal range, LH levels increased and T/LH ratios decreased with increasing FSH levels, while the 170HP/T and estradiol/T ratios were independent of the FSH levels and T/LH ratios. The decreased T/LH ratios in the presence of normal T levels suggest compensated Leydig cell insufficiency, which possibly contributes to the infertility. Indeed, none of the men (n = 12) with normal FSH levels but a T/LH ratio lower than 1.50 achieved fatherhood within 12 months of follow-up, although all other hormonal parameters were within the normal range. During the same period 25 men with T/LH ratios greater than 1.50 succeeded in impregnating their partners (P less than 0.05). In infertile excryptorchid men and even more so in men with Klinefelter's syndrome, plasma T levels and T/LH ratios were significantly decreased, the decrease being greater than in patients with idiopathic azospermia with similar FSH levels. None of the excryptorchid men with normal FSH levels but T/LH ratios below 1.50 fathered a child during the follow-up study. We suggest that the T/LH ratio is an additional useful prognostic parameter of infertility. Plasma T levels were increased in 15% of patients with idiopathic infertility, but increased plasma LH together with increased T levels (increased androgen resistance index) were found in only 1 man. An increased index, however, was found in 6 azoospermic excryptorchid men and 4 of 28 men with Klinefelter's syndrome. Taken together these data suggest that this index is not a reliable parameter of androgen resistance.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Endocrine effects of Trilostane: in vitro and in vivo studies.

Trilostane (4-alpha-5-epoxy-17 beta-hydroxy-3-oxo-5-alpha-androstan-2-carbonitrile) is a modified steroidal molecule. In vitro and in vivo studies in rats have shown that it inhibits adrenal, ovarian and placental steroid synthesis. It seems to act by exerting a selective blockade on 3 beta-hydroxysteroid dehydrogenase. In this study, we investigated whether this molecule interacts with hormone receptors for estrogen, androgen or progesterone. We also tried to demonstrate the effect which Trilostane may have on cellular cultures of human mammary carcinoma (MCF-7 Evsa-T). We also studied hormonal modifications in a series of 12 patients treated with different doses of Trilostane, since this drug is supposed to inhibit the production by the adrenal glands of mineralocorticoids, of glucocorticoids and of the precursors of estrogens. Our results indicate that Trilostane does not react with any of the main hormonal sex steroid receptors, nor does it interfere with cultures of human mammary cancer cells either containing estrogen receptors and therefore allegedly hormone-dependent (MCF-7 line), or estrogen receptor-negative cells, presumably independent of hormonal manipulations (Evsa-T cell line). Finally, endocrine studies on postmenopausal women with advanced breast cancer show that Trilostane significantly reduces the plasma levels of estrone and of its major androgen precursor (androstenedione). However, the latter inhibition is no different from that exerted by hydrocortisone acetate administered alone at a dose of 40 mg/day. The results of clinical trials comparing hydrocortisone alone with hydrocortisone plus Trilostane are awaited.

Antineoplastic Agents↗