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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 19 recordsLinked to original sources

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

Hormonal effects of a 5 alpha-reductase inhibitor (finasteride) on hormonal levels in normal men and in patients with benign prostatic hyperplasia.

Finasteride is a potent competitive 5 alpha-reductase inhibitor, active at a dose as low as 1 mg/day. After a single dose, the effects on 5 alpha-reductase last as long as 7 days. Both hepatic and target tissue 5 alpha-reductase are inhibited. Plasma testosterone and estradiol are unaffected and luteinizing hormone levels do not change. During chronic treatment with finasteride 5 mg/day, the effects on 5 alpha-reductase are maintained. Since the only significant effect of chronic finasteride therapy appears to be 5 alpha-reductase inhibition, and testosterone or estradiol levels are not affected, neither libido nor potency is lost. Testosterone is the active androgen at the muscular level; therefore, muscular catabolism is not expected.

5-alpha Reductase Inhibitors

Influence of age on the responsiveness of the gonadotrophs to luteinizing hormone-releasing hormone in males.

The mechanisms that most likely underly the attenuated response of plasma LH to antiopioids or antiestrogens and the reduced frequency of large amplitude LH pulses in elderly men are decreased LHRH release and/or decreased sensitivity of the gonadotrophs to LHRH. To test the latter hypothesis, the LH response, measured both as bioactivity (B) and immunoactivity (IR), to increasing doses of LHRH ranging from 0.625-5 micrograms, administered as an iv bolus, was evaluated in 10 young (20-45 yr old) and 10 elderly (64-78 yr old) monks. Both basal B- and IR-LH levels were significantly higher in elderly men. The maximal response to each dose was similar in young and elderly men when measured as IR-LH, but the B-LH response was higher in elderly men. The B/IR LH ratio increased with increasing LH levels. The mean half-life of plasma IR-LH in the elderly was significantly longer than that in the group of young men and significantly longer than the mean half-life of B-LH. It is concluded that the sensitivity of the gonadotrophs to LHRH is not decreased in elderly men. This suggests that the attenuated response of LH levels to antiopioids and antiestrogens, respectively, as well as the reduced number of spontaneous high amplitude LH pulses in elderly men may, instead, be the consequence of the release of a decreased mass of LHRH at each pulse.

Adult