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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral↗
PubMed1996

Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males.

Several aspects of the regulation of androgen secretion and plasma levels in males remain controversial. Among these, we cite the problem of whether the age-related decrease in testosterone (T) levels is an intrinsic aging phenomenon or is a sequel of previous illness, the mechanisms underlying the increase in sex hormone-binding globulin (SHBG)-binding capacity in aging men and the supranormal capacity observed immediately after a weight-reducing diet, and the role of insulin in the age-associated decrease in dehydroepiandrosterone (sulfate) [DHEA (DHEAS)] levels. To gain further insight into these issues, we investigated the influence of age, smoking, body mass index (BMI), serum albumin, insulin, GH, and insulin-like growth factor I (IGF-I) levels, respectively, on androgen levels and SHBG-binding capacity in a nonobese healthy population (n = 250) as well as in an obese population (n = 50) before and after weight loss. The influence of GH supplementation on SHBG, DHEAS, DHEA, and insulin levels was studied in a small group of men (n = 8) with isolated GH deficiency. In nonobese healthy men, age was inversely correlated with serum levels of all androgens studied (although total T levels stayed relatively stable until age 55 yr) as well as with albumin, GH, and IGF-I levels and positively correlated with BMI, insulin levels, and SHBG-binding capacity. Nevertheless, SHBG levels were significantly negatively correlated with insulin levels (P < 0.001) as well as with mean 24-h GH and IGF-I levels. Among possible confounding factors affecting (free) T [(FT)] levels in healthy men, smoking appeared to be accompanied by higher (F)T levels than those in nonsmokers. BMI increased with age, but although BMI was negatively correlated with T, FT, and SHBG, respectively, the age-dependent decrease in T levels persisted after correction for BMI. Data not corrected for BMI may, nevertheless, overestimate the age-associated decrease in T levels. The albumin concentration decreased with age, and if FT is the feedback regulator of plasma T levels, albumin concentration might be a codeterminant (although, evidently, less important than SHBG) of T levels and contribute to the age-associated decrease in T levels. In any case, albumin concentration is a codeterminant of DHEAS concentration. T, DHEA, and DHEAS levels were significantly correlated, but this correlation disappeared after controlling for age; hence, there is no evidence for an adrenal-gonadal interaction in men. In obese men, T, FT, and SHBG levels were significantly lower than those in the nonobese men and inversely correlated with BMI; DHEAS levels were slightly lower than those in the nonobese controls, but no significant correlation between DHEA or DHEAS, and insulin levels was observed. After a weight-reducing, protein-rich diet, resulting in a mean weight loss of +/- 15 kg, SHBG-binding capacity increased to normal values notwithstanding the fact that the subjects were still obese and that the insulin levels remained higher than those in the nonobese controls. Considering that after weight loss, GH and IGF-I levels remained lower than those in the nonobese controls, that adult men with isolated GH deficiency presented with higher SHBG levels than normal controls, which decreased to normal levels during GH substitution, and that elderly men have elevated SHBG levels notwithstanding high insulin levels, we suggest that the low GH and/or IGF-I levels might play a role in the elevated SHBG levels observed in both elderly males and obese men after a weight-reducing diet. As weight loss did not influence DHEAS levels notwithstanding an important decrease in insulin levels, our data do not support a role of insulin in the regulation of plasma DHEAS levels.

Adult↗
PubMed1996

Decreased androgen levels and obesity in men.

Obesity in males is accompanied by a significant decrease in testosterone levels. This decrease is essentially a consequence of the decrease of the sex hormone binding hormone (SHBG) binding capacity, itself probably the consequence of the increased insulin levels. In moderate obesity, free testosterone levels are normal, however, and there does not exist a real hypogonadism. In massively obese males, on the other hand, there is real hypogonadotrophic hypogonadism, with decreased free testosterone levels. The latter are the consequence of functional alterations at the hypothalamopituitary pole of the testicular axis, characterized by a decreased amplitude of the LH pulses. The decrease in adrenal androgen (DHEAS) levels is moderate and although it has been claimed that the increased insulin levels may play a causal role, the exact mechanism of this decrease is still a matter of controversy.

Dehydroepiandrosterone↗
PubMed1996

Allergy to pine nuts in a bird fancier.

A patient is described with the bird-egg syndrome who experienced an anaphylactic reaction after eating some of her parrot's food (pine nuts: Pinus pinea). Specific IgE against this nut and another pine nut (P. cembra) was demonstrated by RAST. Cross-reactivity between these botanically related seeds was shown by RAST inhibition. Besides avian antigens, bird food antigens should be taken into consideration when symptoms of allergy occur on exposure to birds.

Anaphylaxis↗
PubMed1995

Which drug to choose for stable angina pectoris: a comparative study between bisoprolol and nitrates.

The choice between beta-blockade or nitrates as first line treatment for stable angina pectoris is based upon the different mechanisms of action and patient characteristics. We performed a clinical trial comparing the efficacy of the longacting beta-blocker bisoprolol once daily and the short acting nitrate, isosorbide dinitrate, three times daily in the reduction of anginal complaints in daily life and under stress. Thirty patients were enrolled in a double-blind randomised cross-over study. Both bisoprolol and isosorbide dinitrate were effective in reducing anginal attacks and nitroglycerin consumption significantly, but bisoprolol was significantly more effective than isosorbide dinitrate. Bisoprolol improved the workload during bicycle exercise testing significantly, but the improvement with isosorbide dinitrate was not significant. Despite the reduction in maximal rate pressure product, bisoprolol was significantly (P < 0.05) more effective at improving total workload and reducing the time to onset of angina than isosorbide dinitrate. The rate pressure product did not change significantly with isosorbide dinitrate. In this study, bisoprolol 10 mg once daily was more effective and caused less side effects than isosorbide dinitrate 20 mg three times a day. It seems questionable if monotherapy of isosorbide dinitrate 20 mg t.i.d is an adequate drug regime for stable angina pectoris.

Adult↗
PubMed1995

Ageing of the hypothalamo-pituitary-testicular axis in men.

In distinction to the course of reproductive ageing in women, men do not experience a rapid decline of Leydig cell function or irreversible arrest of reproductive capacity in old age. Hence, strictu sensu, the andropause does not exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell function do decline with age, as shown by a decrease of +/- 35% of total and of 50% of free testosterone levels between the age of 20 and 80 years. The origin of this decline of Leydig cell function resides on the one hand in the testes, and is essentially characterized by a decreased number of Leydig (and Sertoli) cells and on the other hand in the hypothalamo-pituitary complex characterized by a decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH released at each pulse is also reduced, possibly as the consequence of a reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone below the lower normal limit occur, however, only in a minority of elderly men from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age group over 80 years old. Factors influencing testosterone levels in elderly men are multiple: hereditary, environmental (obesity, stress), psychosocial (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these elderly men should be substituted with androgens remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pathogenesis of the decreased androgen levels in obese men.

In obese men, sex hormone-binding globulin levels (SHBG) as well as total plasma testosterone (T) levels are decreased. Data concerning the levels of nonprotein-bound testosterone (FT) are discordant, with some researchers reporting normal levels, and other reporting decreased levels. The latter imply an impairment of the feedback regulation mechanism of FT levels. We investigated whether an eventual decrease in FT levels and, hence, functional impairment of the gonadostat might occur only at a more severe degree of obesity than that required for a decrease in SHBG and total T levels. We, therefore, determined androgen and precursor levels in three groups of male subjects: nonobese controls [body mass index (BMI), G (kg)/L2 (m) < 26; n = 70]; moderately (BMI, 30-35; n = 18), and severely (BMI, > 40; n = 22) obese men, respectively. In a subgroup of these controls, moderately and severely obese subjects, respectively, we studied LH levels as well as LH pulsatility. Moreover, as a decrease in FT levels might affect the metabolic pattern of the androgens and, more specifically, 5 alpha-reductase activity, we determined the plasma levels of the major 5 alpha-reduced metabolites, androstanediol glucuronide and androsterone glucuronide (AG), as well as the urinary excretion of the major 5 alpha (androsterone glucuronide) and the major 5 beta (etiocholanolone glucuronide) metabolite of the androgens. In moderately obese men, T levels were decreased, which was the consequence of the decreased SHBG-binding capacity. FT levels, however, were normal as were LH levels and both pulse amplitude and frequency of LH pulses, suggesting a normal hypothalamic control of LH secretion. In severely obese men (BMI, > 40), total T, FT, and LH levels as well as LH pulse amplitude were decreased, indicating a functional impairment of the gonadostat. Even in massively obese subjects with decreased FT levels, androgen metabolism and 5 alpha-reductase activity appeared to be normal, as suggested by similar androstanediol glucuronide and AG levels, determined by RIA or calculated from the conversion rates of precursors obtained in nonobese subjects. This was confirmed by the similar AG/eticholanolone glucuronide ratios in obese and nonobese men.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Testosterone concentrations in women and men with NIDDM.

UNLABELLED: OBJECTIVE--To evaluate androgen concentrations in relation to insulin resistance in men and women with and without NIDDM. Recent studies have indicated the potential importance of the regulation of insulin sensitivity by androgens in both women and men. Low sex hormone binding globulin (SHBG) concentration is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in women and is strongly associated statistically with signs of insulin resistance. RESEARCH DESIGN AND METHODS--We compared measurements of anthropometric variables and SHBG, steroid hormone, and insulin concentrations of women and men who have NIDDM with those of control subjects. RESULTS--Women with NIDDM had somewhat higher plasma insulin concentrations, lower SHBG, and higher free testosterone values than did control subjects with similar body mass index (BMI). Women with NIDDM had marginally higher waist-to-hip ratios (WHR). Plasma insulin concentrations correlated positively with BMI, WHR, and free testosterone and negatively with SHBG. In multivariate analyses, insulin concentrations remained positively associated with BMI and free testosterone. Men with NIDDM had higher fasting plasma insulin concentrations than did the nondiabetic control subjects. Testosterone and SHBG were lower in the diabetic men than in both control groups. The derived value of free testosterone was not different between groups. Univariate correlation analyses revealed tight statistical couplings between plasma insulin on the one hand and SHBG and testosterone concentrations (negative) on the other. In multivariate analyses, only the insulin-testosterone association remained. CONCLUSIONS: Women with NIDDM have high levels of free testosterone and low levels of SHBG. Insulin resistance is closely correlated with these signs of hyperandrogenicity as well as with obesity. Men with NIDDM also have low levels of SHBG and, in contrast to women, low testosterone values. Insulin values correlate negatively with these hormonal factors. Based on the results of experimental work and intervention studies, we suggest that these androgen abnormalities might be causally related to insulin resistance in NIDDM.

Androgens↗
PubMed1994

[Neuroendocrinological aspects of aging].

Aging is accompanied by important changes in the production and secretion of hormones. These partly arise from changes in the peripheral endocrine glands themselves but are also partly the consequence of changes in the neuro-endocrine regulating centers of the hormone secretion. Considering e.g. the male gonads, we know that the reduced androgen secretion (and the diminished spermatogenesis) along the ageing process is the consequence of changes in the testes, such as the reduced number of Leydig- and Sertoli-cells, as well as a reduced testicular blood-perfusion. But on the other hand, it should also be partly ascribed to functional changes of the hypothalamohypophysis. This appears from the lowered circadian rhythms of the testosterone levels, the lower plasma levels of free testosterone, although the secretion capacity of the Leydig-cells and the gonadotrophs is maintained. This points to a lower feed-back set-point of the gonadostat. Moreover the amplitude of the LH impulses and the lower opioid tonus are decreased in elderly men. In aged people, the secretion of the adrenal cortex is essentially characterized by an age-related drop of the androgen secretion (DHEAS) and a lower androgens-response to ACTH. This demonstrates changes in the adrenal gland itself. On the other hand, the secretion of cortisol and the production rates of this hormone remain rather stable, although the feedback centre is less sensitive in old lab-animals. This is suggested by a longer lasting and higher cortisol secretion after stress. According to Sapolsky, this is the consequence of a drop in the number of corticoid receptors in the hippocampus, following a loss of neurons, which would be the result of repeated stress. This progressive deterioration of the feed-back locus by the final hormone is also called: "neurohumoral hysteresis". Signs of its existence in aged people can only be found in pathological cases, such as depression or Alzheimer's disease. The secretion of growth hormone, and its plasma levels, as well as their response to "Growth hormone releasing hormone" (GHRH) is severely reduced in old people. This does not appear to be the consequence of the decreased number of somatotropic cells in aged people but seems to be caused by an increased somatostatin secretion by the hypothalamus. It means that this reduced growth hormone secretion has mainly a central origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1994

[Do hormones determine our fate?].

The hormonal system is a communication system between cells and organs. Hence it is not surprising that it influences almost all physiological functions and, at least partially, our behaviour and fate. The sexual phenotype is determined by the sex hormones. Normally, the phenotype is in accordance with gonadal and genetic sex, but occasionally, as a consequence of enzymatic defects in the biosynthesis of sex hormones or of androgen resistance, gonadal and genetic sex are in discordance with the phenotype, the latter determining generally the civil sex and the sex of rearing. Whereas the gender role is generally determined by the sex of rearing and the phenotype, itself under hormonal influence, homo- and transsexuality constitute notorious exceptions to this rule. Although several authors consider homo- and transsexuality to be the consequence of an impairment in androgenic impregnation in the perinatal period, there are at present no convincing arguments for an hormonal origin for either homo- or transsexuality, although such a possibility can't be excluded either. Besides their role in psychosexual behaviour, sex hormones play also a role in our life expectancy. Indeed, although maximal life expectancy of man is genetically determined, a major determinant of individual life expectancy is cardiovascular pathology. The latter is partly responsible for the difference in life expectancy between men and women, cardiovascular mortality increasing rapidly at menopause and being halved by oestrogen replacement therapy. Also atherogenesis as such is, to a large extend, under hormonal control. Indeed insulin resistance and hyperinsulinism, which develop as a corollary of the aging process, is an important cause of atherosclerosis as well as of hypertension. Other hormones also play an important role in our behaviour. We can mention here the role of the thyroid hormones in the physical and mental development of children as well as in the regression of the intellectual functions in hypothyroidism; the role of growth (and sex) hormones in the clinical symptomatology of aging; the memory enhancing effects of the antidiuretic hormone; the role of growth factors (as well as of sex hormones) in tumorigenesis; the role of corticoids (and sex hormones) in the modulation of immunological processes etc. In brief, hormones influence all aspects of our life.

Aging↗
PubMed1993

Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension.

In a group of 36 untreated patients with mild-to-moderate essential hypertension (office systolic blood pressure [SBP] 160 +/- 3.4 mm Hg, office diastolic blood pressure [DBP], 102 +/- 1.5 mm Hg), 24-hour ambulatory blood pressure 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 levels and plasma renin activity. Urinary catecholamine concentrations were assayed from 24-hour urine collections. Left ventricular mass index (143.7 +/- 8 g/m2) did not correlate significantly with either office SBP or office DBP. The correlation of LV mass index with mean 24-hour SBP (145 +/- 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour DBP (90 +/- 3 mm Hg) with r = 0.499 (p = 0.004). Urinary catecholamine levels did not correlate with LV mass index. In addition, LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050) and serum aldosterone levels (r = 0.559, p = 0.0009). There was a strongly significant correlation between LV mass index and serum aldosterone levels even after adjustment for mean 24-hour SBP (r = 0.496, p = 0.005) and DBP (r = 0.514, p = 0.004). These results demonstrate that ambulatory blood pressure determinations but not office blood pressure parameters correlate well with left ventricular hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of left ventricular mass as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Comparison of plasma androgen glucuronide levels after percutaneous or peroral androgen treatment in men: evidence for important splanchnic contribution to plasma 17 beta-hydroxyandrogen glucuronides.

To investigate whether glucuronides of 17 beta-hydroxyandrogens are formed mainly in peripheral tissues or in splanchnic tissues, we compared androstanediol (AD) glucuronide (ADG) and dihydrotestosterone (DHT) glucuronide (DHTG) levels as well as the ratios of glucuronides over free steroids after transcutaneous DHT gel administration to levels and ratios found after oral administration of testosterone undecanoate. Whereas DHT and AD plasma levels were much higher after transcutaneous DHT gel administration, ADG and DHTG levels as well as glucuronide/free androgen ratios were an order of a magnitude higher after oral TU. This indicates that 17 beta-hydroxyandrogen glucuronides cannot be considered specific metabolites of androgen target tissues and are formed to a large extent in the splanchnic circulation.

Administration, Cutaneous↗
PubMed1993

Origin and significance of plasma androsterone glucuronide levels: a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity.

To evaluate the reliability of plasma androsterone glucuronide (ADTG) as a parameter of androgenicity at the target tissue level, we studied the origin of ADTG in women, by measuring the plasma conversion rate of different possible precursors as well as by measuring ADTG levels in ovariectomized women and women with Addison's disease. In women, ADTG levels reflect essentially adrenal androgen secretion, dehydroepiandrosterone sulfate (DHEAS) being the major precursor, accounting for 70%-80% of ADTG levels. As estimated from the ADTG/DHEAS ratio in hirsute women (increased peripheral 5 alpha-reductase) and hyperthyroid women (increased hepatic 5 alpha-reductase), it appears that hepatic 5 alpha-reductase is a major determinant of the conversion of precursors to plasma ADTG. In men, plasma testosterone and DHEAS appear to contribute to a comparable extent to plasma ADTG levels, as suggested by data obtained in orchidectomized men and men with Addison's disease. In accordance with the role of DHEAS as a precursor, plasma levels of ADTG decrease significantly with age in both men and women. Our data do not support the concept that plasma ADTG levels reflect primarily peripheral androgen formation.

Addison Disease↗
PubMed1993

Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men.

To evaluate the effects of obesity on the hypothalamo-pituitary-testicular axis, we compared total and free (FT) testosterone (T), androstenedione, dehydroepiandrosterone and its sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide, and estradiol levels in a group of 35 obese [body mass index (BMI), > 30] men (aged 17-61 yr) to levels in a nonobese control group. We observed a highly significant negative correlation (P < 0.001) between plasma (F)T levels and BMI and a significant positive correlation (P < 0.01) between E2 levels and BMI. There were no differences between the obese and the nonobese men in levels of androstenedione, dehydroepiandrosterone sulfate, and 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide. Insulin levels were significantly higher in obese men and were significantly (P < 0.02) correlated with the waist hip girth ratio. To evaluate the role of the hypothalamo-pituitary complex in the decreased (F)T levels in obese men, diurnal (0800-2000 h) LH pulsatility was studied in eight obese middle-aged men and eight age-matched controls. The pulsatility of plasma cortisol levels was also studied. Whereas LH pulse frequency was similar in the obese and control subjects, mean diurnal LH levels, mean diurnal LH pulse amplitude, and the sum of all diurnal LH pulse amplitudes and secretory masses were significantly lower in the obese than in the controls. Moreover, there was a highly significant correlation between the sum of LH pulse amplitudes and plasma (F)T levels. This decrease in LH pulse amplitude is not an isolated phenomenon of hypothalamo-pituitary dysfunction in obese men, because the pulse amplitude of plasma cortisol levels was also decreased. The decreased LH pulse amplitude together with the normal respond of Leydig cells to hCG stimulation reported in the literature suggest by inference that the decreased FT levels in obese men are the consequence of a hypogonadotropism. The decreased LH pulse amplitude and the decreased amplitude of cortisol pulses, and hence probably of ACTH pulses, point toward a general alteration of hypothalamo-pituitary function in obese men.

Adolescent↗