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Biomedical subjects

A Vermeulen

Publications and source records attributed to A Vermeulen.

At least 19 recordsLinked to original sources

Andropause.

Although, in distinction to middle aged women, in middle aged men there does not occur a sudden arrest of gonadal functions, fertility persisting until very old age, aging in men is, nevertheless, associated with an gradual decline of both endo- and exocrine testicular function. Whereas age has in fact only minimal effects on the quality of the ejaculate, endocrine function declines steadily with age and at age 75 years, mean plasma testosterone levels are only 65% of levels in young adults whereas over 25%, of these men have bioavailable testosterone levels below the lower normal limit in young adults. The interindividual variations in the plasma levels are, however, very important and a quarter of men over 75 years old, have still testosterone levels within the upper quartile of values in young men. Aging is accompanied by a series of signs and symptoms, many of which are rather similar to those observed in young hypogonadal males. The etiology of these signs and symptoms is often multifactorial, and very few correlations have been found between symptoms and plasma testosterone levels. Nevertheless, there is good evidence that the age associated decrease in testosterone levels is at least a co-determinant of these symptoms and testosterone supplementation has shown favorable effects on many of them. Side effects of this substitutive therapy are minimal when care is taken to keep plasma testosterone levels within the physiological range. Clinical prostatic carcinoma is an absolute contra-indication for testosterone supplementation. So far, there are no indications that testosterone would stimulate the evolution of as subclinical prostatic carcinoma to a clinical carcinoma but it should be recalled that so far, only a small number of elderly males received substitutive androgen treatment for longer periods in controlled studies. Hence, although side effects are generally minimal, one should, nevertheless, await the results of larger, long term, well-controlled studies before to recommend the routine testosterone substitution of elderly men.

Aged↗

[Senile hypogonadism in man and hormone replacement therapy].

Aging is accompanied by a progressive decline of testicular function. Whereas fertility persists until a very old age, endocrine function declines progressively and at age 70 yrs, more than 25% of men have hypogonadal testosterone levels. This decline in testosterone plays an important role in a series of signs and symptoms that accompany the aging process such as a decline in virility, in libido and sexual activity, muscle mass and strength, decline in bone mass (osteoporosis), an increase in abdominal fat mass and a decrease in the feeling of general well being. Most of these signs and symptoms have a multifactorial origin, nevertheless, androgen substitution generally improves most of these symptoms, increasing muscle mass and strength, improving libido and sexual activity, decreasing abdominal fat and improving insulin sensitivity as well as the sense of well being, effects which suggest a role of androgen deficiency in their genesis. Side effects of this substitutive therapy, mainly at the level of the prostate, with possible stimulation of a prostatic carcinoma, should be carefully looked for. Before starting any androgen therapy, the presence of a prostatic carcinoma should be excluded by rectal examination and PSA measurement, eventually, in case of doubt, complemented by transrectal echography. Presence of a prostatic carcinoma is an absolute contraindication for androgen therapy. During treatment, development of side effects should be traced by a six monthly rectal examination and PSA determination as well by monitoring of hematocrit and lipid profile.

Aged↗

Oral language acquisition in children assessed with the Reynell Developmental Language Scales.

Oral language development of ten children, prelingually deafened by meningitis, was assessed with a Dutch version of the Reynell Developmental Language Scales. The test was administered pre-operatively and at regular intervals after implantation. The average rate of language development between two consecutive evaluations was computed. This rate was defined as the quotient of the increase of the language age and the increase of the chronological age between the evaluations. A normal language development has a rate of 1; this means 12 months language development in 12 months time. In case of language retardation the rate of language development is less than 1. The rate of receptive language development showed a gradual increase. In the interval between 12 and 24 months of implant use the ratio was 0.9. This implies a language development that is quite similar with the development in normal hearing children. The rate of expressive language development showed a fast improvement in the period between 6 and 12 months after implantation, up to 1.4. If this rate of development continues the children with C.I. will catch up with their normal hearing peers.

Child↗

A critical evaluation of simple methods for the estimation of free testosterone in serum.

The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index ofbioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.

Adult↗

Testosterone, body composition and aging.

In addition to growth hormone (GH), sex hormones are important determinants of body composition. Aging is accompanied by a decrease in free testosterone levels and, as BMI as well as fat mass increase with age (with a redistribution of body fat), whereas muscle mass decreases, it is tempting to attribute a causal role to the decrease in androgen levels. In our study involving 372 males aged >20-85, age was found to be positively correlated with BMI and fat mass as measured by impedance, and negatively correlated with levels of free testosterone and free insulin-like growth factor-I. Multiple regression analysis revealed that BMI and age were independent determinants of testosterone levels. The latter decreased from 598+/-188 (SD) ng/dl in the young controls to 453+/-161 ng/dl in the elderly group, free testosterone decreasing from 15.35+/-4.10 to 8.38+/-2.51 ng/dl. Fat-free mass decreased by 18.9%. In a subgroup of 57 men aged 70-80 years, testosterone levels correlated negatively with percentage body fat (r=-0.57), abdominal fat (r=-0.56) and plasma insulin levels (r=-0.40). As GH levels and pulsatility also decrease with age and as, moreover, androgens amplify endogenous secretion of GH, it is not easy to determine the relative role of androgen deficiency in the age-associated changes in body composition. Moreover, increase in fat mass (obesity), as occurs in aging males, is in itself associated with low levels of free testosterone and GH which both normalize after weight reduction. The role of testosterone in the age-associated changes in body composition is, however, further suggested by the increase in lean body mass and in mid-arm circumference and the decrease in waist-to-hip ratio observed after testosterone treatment of elderly men with decreased testosterone levels. Also in healthy eugonadal men, testosterone treatment, at least in supraphysiological doses, causes an important increase in fat-free mass (+/-10%) and in muscle size. The changes in muscle volume are associated with an increase in muscle fibre diameter, suggesting that testosterone induces muscle cell hypertrophy. In conclusion, aging in males is accompanied by an important increase in fat mass and a decrease in lean body mass. Several indices of body composition are significantly correlated with plasma testosterone levels before and after correction for BMI and age. It is evident, however, that in addition to testosterone levels, the age-associated somatopause is also a determinant of the changes in body composition.

Adult↗

[Cochlear implantation in deaf children].

OBJECTIVE: To evaluate the results of cochlear implantation in deaf children. DESIGN: Descriptive. SETTING: Ear, nose and throat department, Academic Hospital, Nijmegen, and Institute for the Deaf St. Michielsgestel, the Netherlands. METHODS: The results in 29 totally deaf children implanted with a 22-channel Nucleus implant--partly in a project supported by the National Fund for Investigative Medicine--in the period 1990-1996 were determined. Six of the children had congenital deafness, the others were deaf as a sequel to meningitis. The operation had no serious complications. All children were followed for at least two years. Progress in auditory perception and speech-language development were measured with structured tests. RESULTS: There was a marked improvement in auditory performance, and language development (measured with Reynell test), although the level of normal hearing children was not reached by most of the operated children. The results were better for children with total insertion of the electrodes than for those with partial insertion (n = 4); of these last, one stopped using the implant. CONCLUSION: Cochlear implantation can limit the consequences of total deafness in children.

Adolescent↗

A simple analytical method for determining the steady-state potential in models of geometrically complex neurons.

A method is presented for solving the cable equation for a spiking neuron below firing threshold or a nonspiking neuron of arbitrary geometry under constant stimulation. The neuron structure is considered as a tree composed of a set of cylinder cables of three types (terminal, intermediate and branching) characterized by their lengths, diameters and linear membrane properties. The stimulation can result from either a uniform conductance-change over a whole cable segment or a point injection of a current. Other special segments are considered (synapses, voltage clamp, lumped soma). Equations are given for replacing any segment with its Thévenin equivalent, i.e. resistance and electromotive force. The step by step use of these elementary equations allows one to find the Thévenin equivalent of the whole neuron and to determine the steady-state membrane potential at any point.

Algorithms↗

Experimental Induction of Morphological Deformities in Chironomus riparius Larvae by Chronic Exposure to Copper and Lead

Five consecutive generations of Chironomus riparius Meigen larvae were chronically exposed from egg to fourth instar to four sublethal concentrations of copper (0, 1, 10, 100 µg L-1) and lead (0, 5, 50, 500 µg L-1) in artificially spiked water (static with renewal), with diatomaceous earth as substrate and tetraphyl(R) as food, in order to test the induction of morphological deformities by these metals. The use of diatomaceous earth was suboptimal because it caused high mortalities (>60%), independent of metal stress. The higher copper concentrations had a positive effect on the survivals relative to the control. Split medial mentum teeth were recorded in more than 10% of the larvae, but could not be related to metal stress. Deformities of the mentum and the mandibles were recorded in second, third, and fourth instars exposed to both metals. Concentration and generation effects were noted for unusual number of mentum teeth (0-5.3%, lead), unusual number of mandible inner teeth (0-10.4%, copper and lead), and small open mentum gap (0-6.5%, copper). These experiments demonstrated the potential of both an essential and a non-essential metal to induce weak deformities in a small proportion of a C. riparius population as well as the induction of deformities which are independent of metal stress or fluctuating over the generations. The study shows the potential of midge deformities as a biomonitoring tool, but at the same time warns for a careful interpretation of deformity scores because of the influence of population dynamics on the final outcome of deformity frequencies and of the existence of deformities not related to pollution.

Journal Article↗

Dendritic integration in olfactory sensory neurons: a steady-state analysis of how the neuron structure and neuron environment influence the coding of odor intensity.

Response properties of the receptor potential at steady state were analyzed in a biophysical model of an olfactory sensory neuron embedded in a multicell environment. The neuron structure was described as a set of several identical dendrites (or cilia) bearing the transduction mechanisms, joined to a nonsensory part--dendritic knob, soma, and axon. The different ionic compositions of the media surrounding the neuron sensory and nonsensory parts and the extraneuronal voltage sources, which both result from the presence of auxiliary cells, were also taken into account. Analytical solutions were found to describe how the receptor potential at the nonsensory part responds to a uniform change in the odorant-dependent conductance resulting from odorant stimulation of the sensory dendrites. We investigated the influence of various geometrical and electrical parameters on the receptor-potential response in the classical model neuron within a homogeneous environment and in the model neuron surrounded with auxiliary cells. First, it was found that the maximum amplitude of the receptor potential is independent of the neuron structure in the absence of auxiliary cells but not in their presence. In the latter case, the amplitude decreases with the length and number of sensory dendrites and with the input resistance of the nonsensory part. Second, the sensitivity (as measured by the increase in membrane conductance at half-maximum response) of the neuron model in the absence of auxiliary cells is higher, but its dynamic range is narrower than in their presence. The dynamic range is wide and the sensitivity low when the input resistance of the nonsensory part is small and the sensory dendrite is unbranched. Both sensitivity and dynamic range are higher for a longer dendrite. These results help understand the morphology of insect olfactory sensilla and can be generalized to other neuron types.

Animals↗

Prevalence of natural rubber latex allergy (type I and type IV) in laboratory workers in The Netherlands.

The objective of the study was to study the prevalence of Type IV and Type I allergy to natural rubber latex (NRL) in a population at risk in the Netherlands. Laboratory workers regularly using gloves were invited to complete a questionnaire and to be tested. We performed patch tests with standard contact allergens, rubber additives, glove powder and pieces of 4 gloves; prick tests with inhalant allergens, glove extracts, glove powder and fruit extracts; and RASTs. Glove-related hand dermatitis was reported in 36.9% of the individuals interviewed. A positive patch test result for rubber additives was seen in only 6.6%. Glove-related urticaria, rhinoconjunctivitis and/or asthma were reported in 24.6% of all cases. Confirmation of an IgE-mediated reaction was achieved in 8.3% by prick test with glove extracts and 5.0% by RAST. No reaction to glove powder was noticed in patch testing or in prick testing. A high prevalence rate of glove-related symptoms and NRL Type I allergy was found in laboratory workers exposed to rubber gloves. Surprisingly, there was no co-existence of Type I and Type IV allergy in this population.

Adult↗

Clinical and pathological changes in the knee after accidental chlorhexidine irrigation during arthroscopy. Case reports and review of the literature.

We describe six knees in five patients, referred to us after accidental irrigation with chlorhexidine 1% in aqueous solution during arthroscopy. All six knees developed persisting pain, swelling and crepitus with loss of range of movement. Radiographs showed loss of joint space in all three compartments due to extensive chondrolysis, with many loose bodies and synovitis. Histological examination showed partial necrosis of the cartilage, with slight non-specific inflammation and fibrosis of synovial specimens. Care is needed in checking irrigation fluids, and these should have a distinctive colour.

Adult↗

Coding of odour intensity in a sensory neuron.

A deterministic biophysical model of an olfactory sensory neuron under constant stimulation is presented with the aim of describing the successive conversion steps, including receptor activation, conductance change, receptor potential and firing frequency, that are involved in the coding of odorant concentration. This model is divided in two parts. The odorant-sensitive part (OSP), consisting of one cylindrical dendrite, is connected to the odorant-insensitive part (OIP), corresponding to passive dendrite, soma and axon. Each part exerts a specific effect on the coding properties of the conversion steps, i.e. their magnitude, sensitivity and dynamic range. The maximum conductance of the OSP affects positively all coding properties whereas the input resistance of the OIP, which depends on its size and shape, affects positively the sensitivity and negatively the dynamic range. These findings are helpful for understanding the input-output properties of many types of neurons.

Action Potentials↗

Declining gonadal function in elderly men.

Ageing in men is accompanied by a progressive decline of gonadal function with, in particular, a decline of total and free testosterone (T) plasma levels resulting in a significant proportion of elderly men over age 60 years presenting with subnormal T levels compared with the levels in young adults. A great interindividual variation in T levels is observed in elderly men, a variability explained in part by physiological variables and differences in life style, while associated acute or chronic diseases may accentuate the age-related decline of T levels. The progressive decrease of plasma T levels has been shown to result from both primary testicular changes and altered neuroendocrine regulation of Leydig cell function. At present, little is known about the clinical relevance of the relative hypoandrogenism of elderly men and there is an urgent need for more longitudinal studies, which may clarify a possible role of decreased T levels in the modulation of the clinical consequences of ageing in men. In view of the lack of relevant controlled clinical trials having careful assessment of the risks and benefits of androgen replacement therapy in elderly men, this treatment should be reserved for selected patients with clinically and biochemically manifest hypogonadism, after careful screening for contraindications.

Aged↗

Fabry's disease: a multidisciplinary disorder.

Fabry's disease is an X-linked hereditary disorder resulting in accumulation of a glycolipid (galactosylgalactosyl glucosylceramide) due to deficiency of alpha-galactosidase A. The diagnosis can be made by histopathologic examination of skin biopsy, low activity of alpha-galactosidase in leucocytes and genetic examination. Treatment is symptomatic. We want to stress the multidisciplinary collaboration necessary to deal with this condition, in order to prevent acceleration of symptoms.

Adult↗

[Juvenile hormones, reality or myth?].

Recently, the "discovery" of so called "rejuvenating" pills, has attracted much interest in the media and has raised irrational expectations among the elderly population. These so called "rejuvenating drugs" are dehydroepiandrosterone (DHEA), a steroid hormone secreted by the adrenal cortex, and melatonin, an indol derivative, secreted by the pineal gland, both known since many years. Dehydroepiandrosterone is quantitatively by far the most important steroid in the human organism; it is a weak androgen, a small fraction of which is aromatized to estrogens in peripheral tissues. Plasma levels of DHEA decrease with age and some authors consider these levels as a reliable parameters of biological age, the more so that some studies seem to indicate that low levels are accompanied by increased morbidity and mortality. This could not be confirmed, however, by other authors. In in vitro experiments, DHEA has anti-oxidative effects, inhibits platelet aggregation and, possibly, stimulates the immunological system. In animal experiments DHEA has some antitumoral effects. These effects were, however, observed in animal species which do not secrete DHEA. It should, moreover, be mentioned that administration of DHEA in a high dosage, induced the development of hepatic carcinoma in 14 out of 16 rats. Preliminary controlled studies, performed in 30 elderly persons, showed an improvement of general wellbeing with an increase in plasma IGF-1 levels; in women a moderate increase in plasma testosterone and estradiol was observed. Hence these studies show a moderately beneficial effect of DHEA therapy. They need to be confirmed and they warrant further well controlled studies. Melatonin is a hormone secreted by the pineal gland, the releasing stimulus of which is darkness. It synchronizes the biological rhythms as well as the seasonal biological changes induced by the photoperiod. It induces sleep and is an euphoretic. Melatonin plasma concentrations decrease with age and this decrease has been related to the impaired sleep induction in elderly. Melatonin levels are also decreased in depression. In mice, transplantation of the pineal gland of young animals to old animals increases life expectancy by +/-20%. In in vitro experiments, melatonin appears to have some anti-oxidative effects, which led to the hypothesis that it might retard the ageing process and inhibit the growth of tumor cells. In man, melatonin has been shown to be effective in preventing jet lag and in improving sleep induction in the elderly as well as disturbances of the nycthemeral rhythms in blind persons. One research group even reported favourable effects of a combined melatonin-IGF-1 treatment of metastatic carcinomas; these results were not confirmed up to now. As to the advertised effects on sexuality, it is well known that melatonin inhibits gonadotropin secretion, which causes gonadal atrophy. Hence it is evident that we can not expect a stimulation of sexuality by melatonin administration. As to prolongation of life expectancy, there are, so far, no indications for such an effect in man.

Aged↗

Time-dependent solutions for a cable model of an olfactory receptor neuron.

A mathematical model for an olfactory receptor neuron is investigated. The physiological and anatomical background required for the construction of a mathematical model are explained. The model, which has been described previously, has three components, including the sensory dendrite on which are found the receptor proteins themselves, and others consisting of a passive cable leading to a trigger zone and axon. In the present paper, we pursue an analytical approach for determining the change in time of the receptor potential in the important case of a subthreshold square pulse of odorant stimulation delivered uniformly at the sensory dendrite. Then, the input current increases in time to its asymptotic value. This latter condition means that we can use a Green's function approach in order to obtain accurate representations for the solution for the entire length of the nerve cell. In the case of finite cables the solution is obtained as an infinite series which is shown to converge and can be easily used to find the depolarization at all space and time points of interest. A steady-state result is obtained directly by solving the relevant ordinary differential equation. For a semi-infinite cable an explicit expression is found for the voltage as a function of time and space variables involving a single integral. However, the exact expression follows from this for the steady-state result. The analytical results obtained are compared to numerical solutions and employed to investigate the effect of varying the position of the trigger zone and the electronic length of the neuron.

Humans↗