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Biomedical subjects

B Velkeniers

Publications and source records attributed to B Velkeniers.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in parathyroids, enteropancreatic endocrine tissues, anterior pituitary, and other tissues. The gene for MEN1 has recently been cloned and shown to code for a 610-amino acid protein of enigmatic function which probably acts as a tumor suppressor. Several mutations causing the MEN1 phenotype have been recently identified. In order to determine the spectrum of MEN1 gene mutations in a sample of 25 Belgian patients, we have systematically screened the 10 exons and adjacent sequences of the MEN1 gene by means of an automatic sequencing protocol. Twelve different mutations were identified including nonsense, frameshift, splicing, and missense mutations. Two of these mutations (D172Y and 357del4) occurred more than once. A missense mutation was also found in a kindred with familial hyperparathyroidism. We observed no significant correlation between the nature or position of mutation and the clinical status. We have also detected 6 intragenic polymorphisms and DNA sequence variants and have analyzed their frequencies in our population.

Belgium↗
PubMed1999

Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome.

Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency. In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls. We found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome.

Adrenal Glands↗
PubMed1999

Calcitonin reserve in different stages of atrophic autoimmune thyroiditis.

The objective of this study was to determine the calcitonin (CT) hormone reserve in different severity of atrophic autoimmune thyroiditis (AAT). Forty-eight female patients with AAT were divided into four groups based on basal and peak thyrotropin (TSH) values (after oral thyrotropin-releasing hormone [TRH], free triiodothyronine (FT3) and free thyroxine (FT4) ranging from normal in group 1 to overt hypothyroidism in group 4. All had thyroid antibodies. The control group comprised euthyroid females of comparable age, without thyroid antibodies. Basal CT and CT response to calcium infusion (area under the curve) were investigated as parameters of CT reserve. Basal CT was lower in groups 2 to 4 of patients with AAT (compared to controls), but the difference was not significant. Stimulated CT levels were lower (p < 0.05) in all groups of patients compared to controls, with markedly reduced CT-secretory reserve in group 4. Thyroid antibody concentrations and, basal and postinfusion calcium levels were not significantly different among the various groups. In conclusion CT deficiency (especially stimulated values) occurs in AAT and is more severe in hypothyroid patients than in earlier stages of AAT.

Administration, Oral↗
PubMed1999

Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients.

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 microg/L (range, 16-26,250 microg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactinemia or a microprolactinoma, on average, needed only half the dose of cabergoline as those with macroprolactinomas and have a higher chance of obtaining PRL normalization. Cabergoline also normalized PRL in the majority of patients with known bromocriptine intolerance or -resistance. Once PRL secretion was adequately controlled, the dose of cabergoline could often be significantly decreased, which further reduced costs of therapy.

Adenoma↗
PubMed1998

Vertebral morphometric X-ray absorptiometry (MXA): relationship with bone mineral density in perimenopausal women.

OBJECTIVE: To evaluate the relationship between vertebral morphometry and vertebral bone mineral density (BMD) in a population of perimenopausal women. METHOD: We studied 120 healthy women (mean age (S.D.) 53.4 (8.3) years) referred for baseline bone densitometry around the menopause. Morphometric X-ray absorptiometry (MXA) was performed using a Hologic QDR 4500 A apparatus and assessed the anterior, mid and posterior heights of the third lumbar vertebra (L3). The anterior to posterior height ratio (AH/PH index) and the mid to posterior height ratio (MH/PH index) were calculated. Simultaneously, BMD of L3 was measured as antero-posterior dual energy X-ray BMD (AP-BMD DXA) and as lateral DXA BMD (L-BMD DXA). Subsequently, BMD of L3 was measured using single energy quantitative computed tomography, with a Siemens Somatom device (BMD QCT). RESULTS: The AH/PH index ranged from 0.840 to 1.150, with a mean of 0.995, the MH/PH index 0.880-0.980, with a mean of 0.937. The AH/PH index showed significant correlation with either L-BMD DXA (r = 0.54, P < 0.001) or BMD-QCT (r = 0.50, P < 0.001) but not with AP-BMD DXA (r = 0.05). Using an AH/PH index threshold of 0.97 we categorized the subjects into 42 women (group A) with an AH/PH index < 0.97 and 78 women (group B) with an AH/PH index greater than or equal to 0.97. BMD values were found to be lower in group A than in group B. The difference was not significant with AP-BMD DXA (1011.5 (155.7)) versus 988.5 (193.5) mg/cm2, P = 0.47) but reached high significance (P < 0.0001) with L-BMD DXA (797.2 (166.8) versus 462.9 (131.1) mg/cm2) and with BMD QCT (135.5 (24.8) versus 83.6 (18.3) mg/cm3). CONCLUSIONS: These results suggest that the AH/PH index of L3, assessed using MXA, shows some degree of correlation with BMD in perimenopausal women.

Absorptiometry, Photon↗
PubMed1998

Prolactin, growth hormone and the immune system in humans.

Prolactin (PRL) and growth hormone (GH) qualify as lymphoid growth and differentiation factors. Yet, long-standing hyper- or hyposecretion of PRL or GH does not induce any significant alteration of the immune system. Subclinical changes in laboratory parameters (such as chemotaxis or phagocytosis by granulocytes or macrophages or natural killer cell activity) have been reported in some of these conditions. The GH-insulin-like growth factor (IGF)-I axis is dysregulated in ageing, in catabolic states and in critical illness. Immune parameters, such as infection rate, are being monitored during clinical trials with GH or IGF-I. Hyperprolactinaemia may play an aggravating role in systemic lupus erythematosus, in autoimmune thyroiditis and in other autoimmune diseases. The patient may benefit from increased alertness about interactions between the endocrine and immune systems.

Adult↗
PubMed1997

The weight gain and ultimate adiposity in cafeteria diet-induced obesity is unrelated to the central serotoninergic tonus.

Early detection of subjects with a propensity to obesity might be of great help for setting up preventive intervention studies. In this study we tested whether the development of obesity in Wistar rats, given ad libitum cafeteria foods, could be predicted by a low prolactin (PRL) response to 5-hydroxytryptophan (5HTP), as an index of low hypothalamic serotoninergic tonus. Basal and 5HTP-stimulated (50 mg/kg body weight i.p.) PRL were measured by RIA in 15 young male Wistar rats, whose pelleted diet was afterwards supplemented with cafeteria foods. In the tested animals an increase of PRL between 4 and 56 times the basal value was observed 60 min after the 5HTP injection. After 2 months of feeding, marked inter-individual differences in weight gain between the cafeteria fed animals were observed. After 10 months of feeding, median body fat percentage, assessed by dual X-ray absorptiometry, of the overfed rats was significantly higher than that of control animals: median (range): 41.2% (28.9 - 51.5%) vs 25.1 (18.0 - 32.2%) (p < 0.0001). The PRL response at the start of the experiment was neither correlated with the monthly weight increases, nor with the fat mass percentage at the end of the experiment, suggesting that a pre-existing low hypothalamic serotoninergic tonus is probably not involved in the overeating and ultimate overweight of cafeteria diet fed animals.

Adipose Tissue↗
PubMed1997

Two years of replacement therapy in adults with growth hormone deficiency.

OBJECTIVES: Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated. DESIGN: 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months. rhGH (Genotropin/Genotonorm Pharmacia & Upjohn) was given in a dose of 0.25 IU/kg/week sc (1.5 IU/m2/day). MEASUREMENTS: Every 3-6 months body composition was measured using body impedance analysis and general well being was assessed using the Nottingham Health Profile (NHP) and social self-reporting questionnaire. At the same time patients had a full clinical examination and blood was sampled for glucose, HbA1c, IGF-1, creatinine, full blood count, thyroid hormones and liver function tests. RESULTS: With rhGH therapy IGF-1 levels increased from -2.00 +/- 2.60 SDS to 1.47 +/- 2.6 SDS after six months (P < 0.001), continued to rise despite no change in dose to 1.84 +/- 2.8 SDS after one year and remained constant thereafter (1.98 +/- 2.4 after 2 years). 56% of patients ultimately attained supranormal IGF-1 levels (+2 SD), 22% had levels below the mean, of which 9% were below -2 SD. Within 3 months lean body mass (LBM) increased by +5.09% (P < 0.001), total body water (TBW) by +5.40% (P < 0.001), while body fat (BF) dropped by -10.89% (P < 0.001) and waist circumference by -1.42% (P < 0.004). These effects were maintained during the first year of therapy, but the effect was attenuated after 24 months: LBM, +3.91% (P < 0.001); TBW, +3.28%, P < 0.001, BF, -6.42% (P < 0.001) and waist -2.22% (P < 0.009). Individual differences in response were large and could not be predicted by any of the baseline parameters, except for a better response in males. Treatment resulted in a large and progressive improvement on the NHP scale, especially energy, emotions and sleep, but a similar change was also found in patients during placebo treatment. With rhGH the number of full days of sick leave/6 months decreased from 12.17 +/- 3.90 days (SEM) to 7.15 +/- 3.50 days after six months (P = 0.009), 2.93 +/- 1.55 days after 12 months (P = 0.01), 0.39 +/- 0.17 days after 18 months (P < 0.001) and 3.3 +/- 2.51 days after 24 months (P = 0.026). Similarly, the hospitalization rate went down from 14.9 to 7% after 6 months and remained at this level thereafter (P = 0.12). About one third of patients on rhGH experienced fluid-related adverse events, most often within the first 3 months. They usually disappeared spontaneously or responded well to dose reduction. Cumulative dropout rates were 29% after 1 year and 38% after two years. Two thirds of these patients stopped treatment because of insufficient subjective improvement. Neither drop-outs nor fluid retention could not be predicted by any of the baseline parameters. CONCLUSIONS: We confirmed in a large group of patients the beneficial effects of rhGH therapy on body composition, metabolic parameters and general well-being and found a consistent drop in number of sick days and hospitalization rate. These effects were maintained during two years of therapy, except for an attenuation in body composition changes after 24 months. The high incidence of fluid-related adverse events suggests that it may be better to start with lower doses of rhGH and to increase the dose more slowly over a number of weeks. The finding of suboptimal high or low IGF-1 levels in many patients reinforces guidelines not to give rhGH in a weight-dependent dose but to titrate it individually for each patient.

Adult↗
PubMed1995

Differential alternative splicing of PACAP receptor in pituitary cell subpopulations.

The capability of rat pituitary cells to express receptors for pituitary adenylate cyclase activating polypeptide (PACAP) and VIP was evaluated by binding studies and measurement of adenylate cyclase activity on whole gland preparations and by reverse transcriptase-polymerase chain reaction (TR-PCR) using specific primers on preparations from isolated cell populations enriched in PRL- and GH-producing cells. Data obtained on whole gland preparations indicated that selective PACAP receptors (PACAP Type I) predominated. The mRNA coding for PACAP Type I and for the non-selective PACAP receptors Type II VIP2 (but not VIP1) were identified. The mRNA coding for four different spliced variants of the PACAP Type I receptor were detected. In PRL producing cells, three variants and the VIP2 mRNA were detected, whereas in GH-producing cells the mRNA coding for the variant having a 28-amino acid insert (termed HOP) in the third intracellular loop was the only present.

Adenylyl Cyclases↗
PubMed1995

Identification of a new chromogranin B fragment (314-365) in endocrine tumors.

A rabbit antiserum was raised against the fragment (350-365) of human chromogranin B corresponding to the C-terminal end of a putative proteolytic fragment generated by the cleavage of a dibasic doublet located in position 366-367 of the precursor. A radioimmunoassay was developed. Chromatographic analysis of 10 endocrine tumor extracts (one liver metastasis of a gastrinoma, one liver metastasis of a medullary carcinoma of the thyroid, one VIPoma, one insulinoma, one nonsecreting pancreatic endocrine tumor, one local recurrence of a gut carcinoid, two pituitary gonadotropinoma, and two non-secreting pituitary adenomas) revealed the presence of two forms of immunoreactive material. The most abundant form had an apparent molecular weight of 4500 and was purified to homogeneity by successive reverse-phase HPLC chromatographies and partially sequenced. The N-terminal sequence of the peptide, established by automated Edman degradation, was A-S-E-E-E-P-E-Y-G-E-E-I-K-G-Y-P-V-Q and corresponded to the 314-332 sequence of human chromogranin B. Taking into account the specificity of the antiserum used for peptide identification, we deduced that the purified peptide was chromogranin B(314-365) and represented a new form generated by limited proteolysis of chromogranin B.

Adenoma↗
PubMed1995

Expression of pituitary adenylate cyclase activating polypeptide and receptors in human brain tumors.

The capacity of brain tumor samples to synthesize pituitary adenylate cyclase activating polypeptide (PACAP) was evaluated by the reverse transcriptase-polymerase chain reaction technique (RT-PCR). The expression of PACAP receptors was assessed by a combination of RT-PCR techniques, conventional binding techniques, and also by the ability of PACAP to stimulate adenylate cyclase activity. A weak PACAP mRNA and PACAP receptor mRNA expression was detected in only 3 of 16 meningiomas. A weak PACAP-stimulated adenylate cyclase activity (+20%) was detected in 10 of the 16 samples but binding of labeled PACAP was never observed. In the 16 gliomas studied (including two oligodendrogliomas and two ependymomas), PACAP mRNA was identified in 13 samples and PACAP receptor mRNA in 15 samples. PACAP receptors were identified in all the samples by binding studies and/or by PACAP stimulation of the adenylate cyclase activity. PACAP mRNA was never detected in pituitary adenomas (three prolactinomas, two mixed PRL-GH-producing tumors, three GH-secreting tumors, three gonadotrophinomas, one ACTH-producing tumor, two nonsecreting tumors) whereas PACAP receptor mRNA was highly expressed in all the tumors except prolactinomas, where it was at the limit of detection, confirming the binding and adenylate cyclase activation results. Thus, it is unlikely that the neuropeptide PACAP could influence meningioma's cell growth; PACAP secreted from extratumoral areas may influence pituitary tumors and PACAP could participate to gliomas development.

Adenoma↗
PubMed1995

Cyclosporin A, rapamycin and FK506 decrease prolactin release from rat pituitary cells in primary culture.

It is at present well established that prolactin exerts a non-specific immunoactivating function. In this work we tested whether the immunosuppressant drugs cyclosporin A, FK506 and rapamycin influence prolactin release from rat pituitary cells in primary culture. The tested drugs had no effect on the prolactin release measured during a 2h incubation period, indicating that they do not influence the secretion of prolactin from intracellular stores into the culture medium. During longer incubation times (48h), however, prolactin release was diminished to 56% +/- 18 (10 microM cyclosporin A), 64% +/- 14 (1 microM rapamycin) or 64% +/- 7 (1 microM FK506), suggesting an effect on prolactin production. At these drug concentrations no toxic effects were observed. The data indicate that inhibition of pituitary prolactin synthesis might contribute to the immunosuppressant action of cyclosporin A, rapamycin and FK506.

Animals↗
PubMed1995

Prolactin and growth hormone mRNA and protein characterization in SMtTW rat pituitary tumours.

We have combined different techniques to analyse passages of five different rat spontaneous pituitary tumours (SMtTW) that were transplanted under the kidney capsule. These tumours were secreting prolactin (PRL), GH or both hormones. RIA, immunocytochemistry (ICC) and Western blot analysis were applied to characterize the hormone(s) stored (ICC and Western blot) and secreted (RIA). mRNA content was analysed by PCR, Northern blot analysis and in situ hybridization. The data point not only to the reliability of the techniques used at both protein and RNA levels for each tumour studied but also to the complementarity of some techniques. For example, whereas Northern blot analysis demonstrates the presence and size of hormone mRNA, in situ hybridization indicates the percentage of cells expressing a given hormone mRNA and allows the presence of one population (or more) of cells in a given tumour to be identified. Moreover, the tumours were compared with normal rat pituitary. Although the PRL and GH mRNAs were identical in size, the amount of mRNA was lower in the tumours. At the protein level, the PRL and GH variants exhibited a different pattern of expression in tumours compared with the normal rat pituitary. The biological significance of these differences is discussed.

Animals↗
PubMed1994

5-Hydroxytryptophan-stimulated prolactin levels in cafeteria diet fed rats: an in vivo evaluation of the central serotonergic tonus.

Hyperphagia in rats fed a cafeteria diet might be related to the palatability of the diet or to diet-induced changes in central neurotransmitters regulating the feeding behavior. In this study the central serotonergic tonus in adult male Wistar rats was evaluated in vivo after 6 weeks of feeding a cafeteria diet by the prolactin response to the administration of 5-hydroxytryptophan (5HTP), the immediate serotonin precursor. Blood was taken just before, 30, 60 and 90 min after the ip injection of 50 mg/kg 5HTP for the determination of prolactin concentrations were comparable between cafeteria fed rats and control rats, fed normal laboratory chow (12.7 +/- 5.4 vs 7.7 +/- 4.5 ng/ml). The 5HTP-stimulated prolactin secretion in the cafeteria diet fed rats, determined by the peak value (95.8 +/- 17.2 vs 119.1 +/- 27.0 ng/ml) as well as by the integrated area under the curve (5478 +/- 774 vs 5916 +/- 2275 ng/ml. 90 min) was not significantly lower than in the control rats. In conclusion, our results did not show a significantly decreased 5HTP-induced prolactin release in cafeteria-fed rats, suggesting that a low hypothalamic serotonergic tonus is probably not involved in the overeating of this dietary-induced obesity model.

5-Hydroxytryptophan↗
PubMed1994

Upper airway obstruction due to inoperable intrathoracic goitre treated by tracheal endoprosthesis.

Thyroidectomy is the treatment of choice in patients with thyroid enlargement complicated by compression or displacement of the trachea because of the risk of complete airway obstruction due to sudden enlargement of the goitre by, for example, haemorrhage. In patients who are medically inoperable an endoscopically inserted tracheal endoprosthesis may provide longstanding airway patency, as reported here.

Aged↗
PubMed1994

Expression of IL-6 mRNA in normal rat and human pituitaries and in human pituitary adenomas.

Cells expressing IL-6 mRNA were detected by in situ hybridization in normal pituitaries. In normal untreated rat pituitary the expression was very low. Within hours after IP administration of liposaccharide, IL-6 mRNA accumulated in the anterior lobe of the pituitary. Production of IL-6 was monitored after dissociation and culture of pituitary cells. High levels (8000 pg/ml) were recovered after 72 hr in culture. In normal human pituitaries, less than 1% of cells expressed IL-6 mRNA or IL-6 receptor mRNA (IL-6-R mRNA). In gonadotropinomas, prolactinomas, and non-functioning adenomas, only rare, scattered positive cells were found for either IL-6 or IL-6-R. In contrast, both genes were highly expressed in ACTH- and GH-secreting tumors at the junction of adenoma and infiltrating fibrous tissue and around blood vessels. The combined expression of IL-6 and IL-6-R suggests that IL-6 acts in an autocrine or in a paracrine way in ACTH and GH adenomas.

Adenoma↗
PubMed1994

Functional heterogeneity with respect to oestrogen treatment in prolactin cell subpopulations separated by Percoll gradient centrifugation.

The effects of oestradiol on prolactin gene expression were studied by quantitative in situ hybridization histochemistry in different prolactin pituitary cell (sub)populations, which had been obtained by separation on a discontinuous Percoll gradient. When cells were incubated in vitro in the presence of oestradiol (10(-8) M) for a period of 4, 24, 48 and 72 h, there was an increase in the amount of prolactin mRNA, from 24 h on, only in high-density prolactin cells and lactotrophs of the total cell suspension. In contrast, the amount of prolactin mRNA in lactotrophs of low density did not change upon treatment with oestradiol. Pharmacological treatment with 50 micrograms oestradiol/day (s.c.) of random cycling female rats in vivo for 14 days increased the total number of prolactin gene-expressing cells and more lactotrophs were recovered at high density after Percoll gradient centrifugation. These results suggest a preferential stimulatory effect of oestradiol on prolactin gene transcription on a subpopulation of lactotrophs. Changes observed in prolactin cell layers after oestradiol treatment in vivo may represent a preferential effect in situ on a particular mammotroph cell subpopulation.

Animals↗