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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 73 records · Page 4Linked to original sources

Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

[Metabolic effects of obesity in men].

Obesity is a product of welfare. About 1/3 of our population has got excessive weight, 6 to 8% is truly obese and in 0.1% we may speak of pathologic obesity. Obesity is not only an esthetic problem, but is goes together with higher morbidity and mortality. In men with a body mass index (BMI = W (kg)/L2 (m)) of more than 35, the glucose metabolism was disturbed in 70%, the lipid spectrum had a clearly atherogenic profile, the average (free) testosterone level was significantly diminished and there was also a certain degree of hypogonadism. A short term treatment (4 to 6 weeks) based on a hypocaloric diet (400) and rich in proteins normalized the glucose metabolism in a very great number of patients, while the insulinemia fell with 40% and the lipidogram always became normal, but for the HDL-C, which showed a slight drop, while the testosterone levels became normal with a strong rise of the sex hormone binding globulin. And yet, at that very moment the patients were still definitely obese: this suggests that the metabolic disturbances are not the consequence of obesity in itself, but may be related to the dietary habits of the patients. Concerning the mechanism of hypogonadism, the cause of its disturbance seems to be situated in the hypothalamo-hypophyseal area and be characterized by a lower amplitude of LH-pulses, which are correlated with the testosterone levels. This hypothalamic disorder is however not limited to the LH-secretion, but the amplitude of growth hormone- and of ACTH-pulses is also reduced. Our study suggests that not obesity itself, but dietary factors might be responsible for the detected abnormalities. This might have important implications. Indeed, it is well known that in population groups, whose diet contains fewer calories and less fat--such as the Chinese and the Japanese--sex hormone binding globulin exists in far higher concentrations whereas free testosterone is found in a lower concentration. In these populations the prevalence of clinically obvious prostate cancer--which is androgen-sensitive--is much lower than in Western countries: it seems obvious to look for a correlation between both observations. Another remarkable phenomenon is the difference in testosterone metabolism between the Eastern and Western people; this leads us to the remarkable findings that in Asian people the same amount of androgens nearly always produces azoospermia and infertility, whereas this appears in only 2/3 of the cases among Western people.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗

The male climacterium.

In contrast to women, fertility in men persists until a very old age. However, testicular function of both the exo- and endocrine compartments decreases in old age, causing a series of clinical symptoms which are analogous to, although less pronounced than, the menopausal syndrome. These symptoms can be considered to represent the male climacterium or andropause. However, whereas at menopause ovarian hormonal secretion ceases almost completely, the decrease in the levels of biologically active endrogens (free testosterone) is only moderate and many elderly men have free androgen levels that would be considered normal for young men. Moreover, whereas many well-controlled studies have shown the benefit of hormonal replacement therapy, at least for symptomatic posmenopausal women, so far no well-controlled studies exist that prove a favourable risk/benefit balance of androgen substitution in elderly men. The major risk is the potentially stimulating effect of androgens in elderly men who frequently present with subclinical prostatic carcinoma. Therefore, the generalized use of androgen substitution in elderly men cannot, as yet, be recommended.

Aged↗

Positron emission tomography study of the human hypothalamus during normal ageing and in ischemic and degenerative disorders.

Regional blood flow and oxygen metabolism were determined by positron emission tomography, using the steady state technique with 15O, in the hypothalamus and in the whole brain of fifty two normal persons and patients suffering from cerebral ischemia and degenerative dementia. During normal ageing regional blood flow and oxygen consumption appeared to increase slightly in the hypothalamus and to decrease in the whole brain in 24 persons. In the young age group the hypothalamus was more protected against ischemia than in the elderly group. In the aged group with cerebral ischemia and degenerative dementia regional blood flow and oxygen consumption were decreased in the hypothalamus to the same extent as in the whole brain.

Adult↗

Increased free testosterone but normal 5 alpha-reduced testosterone metabolites in obese premenopausal women.

OBJECTIVE: The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN: As in hyperandrogenicity there generally exists evidence for increased 5 alpha-reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS: Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTS: Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS: Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01). CONCLUSIONS: These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Effects of weight loss on the fatty acid composition of serum lipids in obese women.

The effect of a weight reduction regimen, consisting of a protein-sparing modified fast and an exercise program, on the fatty acid composition of serum phospholipids and cholesterol esters of obese women, is described. In phospholipids, this treatment did not induce any significant change of the different fatty acid families (total saturated, monounsaturated, omega 9, omega 7, omega 6 and trans-fatty acids), except for total omega 3 fatty acids which increased. Within families, individual fatty acids change however. The changes are compatible with increased delta 5 and delta 6 desaturase activity. In cholesteryl esters, significant changes occurred which are suggestive of an increase in serum of the fraction of cholesteryl esters of intracellular origin. The changes in fatty acid compositions may not be beneficial with respect to atherosclerosis.

Adolescent↗

Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset.

In order to determine whether growth hormone (GH) deficiency of childhood onset affects the adult bone mineral status, we assessed bone mineral content (BMC) by photon absorptiometry in 30 full-grown GH-deficient men (8 with isolated GH deficiency and 22 with multiple pituitary deficiencies; 28 previously treated with GH) and in 30 male controls matched for age (within 4 yr) and height (within 10 cm). Forearm BMC was measured by single photon absorptiometry just proximally of the distal one third of the nondominant forearm (PBMC-2 in arbitrary units and PBMC/bone width (BW) after normalization for bone width) and at a more distal site, close to the carpal joint (DBMC-2 and DBMC/BW). Lumbar BMC was measured by dual photon absorptiometry and reported as total BMC for L2-L4 (LBMC in g) and after normalization for projected area (LBMD in g/cm2). The patients had a significantly lower BMC, both at the forearm (P less than 0.0001) and at the lumbar spine (P less than 0.005): 35.7 +/- 1.0 vs. 50.0 +/- 1.6 and 36.9 +/- 1.2 vs. 52.8 +/- 1.9 (mean +/- SEM) for PBMC-2 and DBMC-2 in patients and controls, respectively; 1.36 +/- 0.03 vs. 1.70 +/- 0.04 and 1.07 +/- 0.03 vs. 1.35 +/- 0.04 for PBMC/BW and DBMC/BW; 34.00 +/- 1.08 vs. 42.02 +/- 1.27 g for LBMC and 0.886 +/- 0.016 vs. 0.976 +/- 0.018 g/cm2 for LBMD. Both the patients with isolated GH deficiency and the patients with multiple pituitary deficiencies were osteopenic when compared to their respective controls (P less than 0.01 to P less than 0.0001 for the patients with multiple deficiencies; statistical significance reached for PBMC-2, DBMC-2, and DBMC/BW only, P less than 0.05, in the small group of patients with isolated GH deficiency). For the patients (n = 19) who had at least three serial measurements over a period of 6 to 28 months, no decrease in BMC was detected. Our findings indicate that men with GH deficiency of childhood onset present with a low adult bone mass, despite prior GH substitution in most of these subjects. The observations of a more pronounced bone mineral deficit at the forearm (20-30% lower mean values, depending on the type of measurements) than at the lumbar spine (9-19%) and the findings of osteopenia in both the patients with isolated GH deficiency and multiple pituitary deficiencies, support the view that GH deficiency per se is responsible for part of the observed deficit.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Representativeness of a single point plasma testosterone level for the long term hormonal milieu in men.

To test the reliability of a single plasma testosterone (T) or dihydrotestosterone (DHT) level, respectively, as a parameter of the long term hormonal milieu, plasma T and DHT levels were measured eight times, over a period of 50 weeks, in 169 middle-aged and elderly men with symptomatic benign prostatic hyperplasia, who were otherwise healthy. The results show an excellent correlation (r = 0.849) between plasma androgen levels at first sampling and the mean of the 7 samples taken subsequently over 1 yr. Of the 22 subjects with plasma testosterone levels below the lower limit of normal (10 nmol/L) at first sampling, none had an annual plasma T value greater than 13.5 nmol/L, i.e. the annual mean was also below the normal limit or in the low normal range, whereas of the 18 subjects with a T level at first sampling above 25 nmol/L (+/- 90th percentile), none had a mean plasma T level below 19.0 nmol/L (70th percentile). Similar results were obtained for DHT. When plasma testosterone levels at first sampling were subdivided into groups, with a concentration interval of 5 nmol/L from 5 to more than 25 nmol/L, multifactor analysis of variance showed no significant difference between the values within the same group at each sampling, whereas at each sampling the groups remained highly significantly (P less than 0.001) different from each other. The same applies to DHT levels when subdivided into groups with a concentration interval of 0.5 nmol/L. It is concluded that in healthy middle-aged and elderly men, single point plasma androgen measurements reflect fairly reliably the annual mean androgen level.

Adult↗

Increased plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide concentration in clinically euthyroid women with suppressed plasma thyrotropin levels: further evidence for generalized tissue overexposure to thyroid hormones in these subjects.

It has been reported that plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) are increased in thyrotoxic patients. The present study was carried out to determine whether in clinically euthyroid subjects with suppressed TSH levels, ADG plasma levels would also be increased, suggesting a more generalized tissue overexposure to thyroid hormones. The latter has been suggested from increased sex hormone-binding globulin levels (SHBG) in these subjects. ADG and SHBG levels were measured in a group of 20 euthyroid postmenopausal women, 20 postmenopausal women with clinically evident thyrotoxicosis, and 16 euthyroid postmenopausal women with suppressed TSH levels. The mean ADG level in the thyrotoxic group was 4 times the mean level in the control group, whereas in the group with isolated TSH suppression the mean level was about twice the level in the control group. As levels of dehydroepiandrosterone sulfate, the major precursor of plasma ADG, were not significantly increased in these subjects, these data suggest an increased conversion of dehydroepiandrosterone sulfate to ADG. Together with the increased SHBG levels observed in both thyrotoxic and euthyroid subjects with suppressed serum TSH concentrations, these data support the concept that the TSH-suppressed euthyroid subjects have generalized increased thyroid hormone effects on peripheral tissues.

Aged↗

Isolated early response after nasal allergen challenge is sufficient to induce nasal hyperreactivity.

Ten rhinitic patients allergic to grass pollen were challenged with histamine intranasally 24 hours before and 24 hours after nasal provocation with grass pollen. Up to ten hours after allergen provocation nasal lavage fluid was obtained to characterize early and late phase reactions by measuring the levels of histamine and leukotrienes as indicators of mediator release, and albumin as a marker of increased vasopermeability. Ten minutes after allergen challenge with 10,000 BU grass pollen extract LTC4,D4, and albumin significantly increased from 62 to 576 pg/mL (P = .008) and from 15 to 81 micrograms/mL (P = .008), respectively, without significant changes after placebo challenge a week earlier. Although the patients showed increased responsiveness to histamine after allergen challenge compared with a placebo-challenged control group (P = .02), one patient only demonstrated a late phase nasal allergic reaction characterized by recurrence of clinical symptoms eight to ten hours after allergen challenge and recurrence of mediators in lavage fluid. It is concluded that an isolated early response after allergen challenge is sufficient to induce nasal hyperreactivity. A biochemically or clinically defined late phase allergic reaction does not necessarily accompany allergen-induced hyperreactivity.

Adolescent↗

Influence of the arterial blood pressure and nonhemodynamic factors on left ventricular hypertrophy in moderate essential hypertension.

In a group of 36 untreated patients with mild to moderate essential hypertension (office systolic and diastolic blood pressures (BPs) 160 +/- 3.4 and 102 +/- 1.5 mm Hg, respectively), a 24-hour ambulatory BP monitoring and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone, plasma renin activity and serum parathyroid hormone. Urinary catecholamines were sampled for 24 hours. LV mass index (143.7 +/- 8 g/m2) did not correlate significantly either with office systolic or diastolic BP. The correlation of LV mass index with mean 24-hour systolic BP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour diastolic BP (90 +/- 3 mm Hg) with r = 0.500 (p = 0.004). Urinary catecholamines were not correlated with LV mass index. LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050), and aldosterone (r = 0.559, p = 0.001). There was a very significant correlation between LV mass index and parathyroid hormone (r = 0.719, p = 0.00001) even after adjustment for mean 24-hour systolic and diastolic BPs. These results clearly demonstrate that ambulatory BP determinants but not office BP parameters are well correlated with LV hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of LV mass as well. Besides the renin-angiotensin-aldosterone system, parathyroid hormone appears to play an important role in cardiac hypertrophy.

Adult↗

Is plasma 5 alpha-androstane 3 alpha, 17 beta-diol glucuronide a biochemical marker of hirsutism in women?

We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism (n = 24) or hirsutism associated with polycystic ovary syndrome (n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 micrograms), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cyproterone acetate and ethinylestradiol decreases 5 alpha-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.

Adult↗

Physiopathology of plasma androstanediol-glucuronide.

Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5 alpha-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to +/- 30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5 alpha-reductase activity in peripheral tissues inclusive of the liver.

Adolescent↗

Work resumption and leisure activities after cardiac rehabilitation: the development of criteria to measure social recovery.

In a multicentered trial, the authors investigated 280 cardiac patients to determine the level of recovery of their social life after they had completed a physical training program. Data on work and leisure activities (sports, hobbies, social contacts, and odd jobs) were obtained immediately before and after rehabilitation and again 12 months later by means of semistructured interviews and an inventory of leisure activities. For the analysis of leisure variables, they developed a classification procedure to assign patients to one of five categories indicating an unchanged good outcome, significant recovery, nonparticipation, significant deterioration, or an unchanged poor outcome. The results after rehabilitation showed that some patients had benefited more than others. In addition, improvement or deterioration in one aspect of social recovery appeared to be independent from other aspects. Further systematic research is needed to determine which factors influence the amount of benefit derived from rehabilitation.

Adaptation, Psychological↗

Diagnostic approach to patients with primary hyperaldosteronism.

We report the case of a 38-year-old patient with primary hyperaldosteronism. The diagnosis was made by the demonstration of a non-suppressible high aldosterone level in association with a hypokalemia, an inappropriate kaliuresis and low plasma renin activity. As the choice of the therapeutic approach is dictated by the subtype, further investigation was needed. Using a number of hormonal studies and noninvasive imaging techniques, we could establish the diagnosis of adrenocortical adenoma. Histological examination confirmed our diagnosis. We further discuss briefly the characteristics of the four subtypes of primary hyperaldosteronism and show that the used biochemical markers and imaging techniques are able to differentiate them.

Adenoma↗

Influence of nonhemodynamic factors on the microcirculation in moderate arterial essential hypertension.

This study is aimed at examining the role of non-hemodynamic factors on the impaired microcirculation in patients with moderate essential hypertension. In a series of 31 patients (mean age, 47.8 +/- 1.1 years) with newly diagnosed untreated moderate essential hypertension (mean systolic blood pressure 161.7 +/- 2.0 mm Hg, mean diastolic blood pressure 102.4 +/- 1.5 mm Hg), parameters of the capillaroscopic examination of the finger microcirculation (mean number of capillaries, NRCAP), length of the capillaries (LECAP, microns), diameter micron) of the efferent (EFDI) and afferent (AFDI) apillaries, and mean red blood cell velocity (RBCV, microns/sec), which was measured by the flying spot technique, were correlated with a number of hormones (sampled after an overnight fast) including: plasma renin activity, aldosterone, and parathyroid hormone (PTH). A significant correlation (P less than .05) could be obtained between several parameters of the microcirculation and PTH:PTH (23.8 +/- 1.4 pg/mL)-NRCAP (14.9 +/- 0.5): r = -0.440, P = .013; PTH-AFDI (4.0 +/- 0.5 microns): r = 0.442, P = .012; PTH-EFDI (2.8 +/- 0.5 microns): r = 0.416, P = .019; PTH-RBCV (711 +/- 69 microns/sec): r = -0.351, P = .05. Furthermore, 24-h urinary norepinephrine (U-NOR) and afferent and efferent diameter of the capillaries intercorrelated significantly: U-NOR (46.0 +/- 6.2 micrograms/24 h)-AFDI: r = 0.439, P = .034; U-NOR-EFDI; r = 0.462, P = .025. This study shows that in patients with moderate essential arterial hypertension nonhemodynamic factors have an influence at the level of the microcirculation.

Aldosterone↗