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Biomedical subjects

B Velkeniers

Publications and source records attributed to B Velkeniers.

At least 19 recordsLinked to original sources

Is systematic screening for thyroid disorders indicated in subfertile men?

CONTEXT: Data on the prevalence of thyroid disorders in male subfertility remain scarce. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid autoimmunity in men with normal and abnormal semen characteristics. SETTING: Tertiary referral center for reproductive medicine of the University Hospital AZ-VUB, Brussels, Belgium. PATIENTS AND DESIGN: Two hundred and ninety-two men were stratified according to the presence of normal (group 1; n = 39) or abnormal (group 2; n = 253) semen characteristics. Thyroid function was assessed by serum thyrotropin (TSH) and free thyroxine (FT4), and thyroid peroxidase antibodies (TPO-Ab) for thyroid autoimmunity (TAI or TPO-Ab > 34 kU/l); both were correlated with semen characteristics. MAIN OUTCOME MEASURES: Semen characteristics were determined by World Health Organisation criteria (rapid + slow motility > or = 50% and concentration > or = 20 x 10(6)) and Kruger criteria (morphology > or = 14% normal cells). RESULTS: In group 1, the mean (+/- s.d.) age was 33 +/- 4 years; serum TSH was 1.6 (0.3-29.6) mU/l (median (range)) and FT4 was 12.2 (8.8-15.6) ng/l. In group 2, the mean age was 33 +/- 5 years, serum TSH was 1.3 (0.3-5.2) mU/l and FT4 was 12.5 (8.4-17.5) ng/l; (compared with group 1 P = 0.008 for TSH and P = 0.037 for FT4). In both groups, one patient had increased TSH (2.6% and 0.4%; P = not significant (ns)). In group 1, one patient had TAI and in group 2 twelve patients had TAI (2.6% compared with 4.7%; P = ns). FT4 was an independent determinant for semen characteristics. CONCLUSIONS: The prevalence of thyroid dysfunction and autoimmunity is comparable between men with normal and abnormal semen characteristics. On the basis of these data, we do not advise systematic screening for thyroid disorders in subfertile men consulting a tertiary referral center for reproductive medicine.

Adult↗

Glomerular filtration rate in patients with Cushing's disease: a matched case-control study.

BACKGROUND: Patients with Cushing's disease have a high prevalence of atherosclerosis and maintain an increased cardiovascular risk even after cure of the disease. However, the impact of Cushing's disease on renal function remains to be quantified. OBJECTIVES: To evaluate glomerular filtration rate (GFR) and to identify predictors of GFR in patients with Cushing's disease. DESIGN AND METHODS: We conducted a matched case-control study: 18 patients with active or cured Cushing's disease were compared with healthy population controls matched for age and sex. The main outcome measures were GFR and micro-albuminuria. RESULTS: Patients with Cushing's disease had a lower GFR, as measured by 24-h creatinine clearance (79 versus 95 ml/min per 1.73 m2, P = 0.005) and estimated by the MDRD2 formula (75 versus 88 ml/min per 1.73 m2, P = 0.008). Multiple regression analyses indicated that disease duration was the strongest predictor for a worse GFR. The prevalence of micro-albuminuria was low (5.5% in both groups). CONCLUSIONS: Patients with Cushing's disease have a decreased GFR. Even if they are cured, close follow-up with strict control of cardiovascular risk factors and monitoring of GFR seems mandatory. Furthermore, the dosage of certain drugs should be adapted to the individual GFR.

Adenoma↗

[Scientific education of the candidate specialist in training].

Scientific education is an essential component of the post-graduate training. Fluency in the language of sciences is necessary to understand scientific progress and to translate new scientific advances at the level of medical practice. To reach this goal, specific research skills and participation in research projects should be introduced in postgraduate training. Lack of dedicated time and interest are major barriers in implementing systematically research in the curricula. Some suggestions are made in order to improve research training in the postgraduate programs.

Belgium↗

Efficacy and tolerability of lanreotide Autogel therapy in acromegalic patients previously treated with octreotide LAR.

OBJECTIVE: This open label, multicentre study was designed to evaluate the efficacy and tolerability of lanreotide Autogel (L-Autogel) in acromegalic patients over a 24-week period. The outcome of treatment with this new, long-acting, aqueous formulation of lanreotide was also compared with the patients' previous treatment with octreotide long acting repeatable (LAR). DESIGN AND METHODS: Twenty-five acromegalic patients (13 males, mean age 51+/-12 years) were switched from octreotide LAR (20-40 mg/4 weeks for at least 6 months) to L-Autogel, given deep subcutaneously at a fixed dose of 90 mg/4 weeks. After 12 weeks, the dose of L-Autogel was titrated according to patients' mean GH and IGF-I levels at week 8. It was increased to 120 mg/4 weeks if GH>2.5 microg/l or if IGF-I was above the age-adjusted normal range. It was reduced to 60 mg/4 weeks if mean GH<1 microg/l and IGF-I was within the normal range. If the values did not fall within these ranges, the dose remained unchanged at 90 mg. RESULTS: After 24 weeks of treatment with L-Autogel (final doses 60 mg in 3 patients, 90 mg in 4 patients and 120 mg in 18 patients), mean serum GH (2.9+/-2.4 microg/l) and IGF-I concentrations (332+/-193 microg/l) remained statistically unchanged when compared with baseline values under octreotide LAR (GH 2.4+/-1.8 microg/l and IGF-I 337+/-201 microg/l, non significant (NS)). There was a significant improvement of the acromegalic symptom score over the study period, from 4.8+/-3.4 to 2.8+/-2.5 (P<0.001) and a small but significant reduction in the residual pituitary tumour volume (P<0.05). Local side-effects were observed less frequently and no technical problems were encountered with the L-Autogel injections, as opposed to treatment with octreotide LAR (60 difficult injections/150 (P<0.001)). CONCLUSIONS: L-Autogel appears to be as effective as octreotide LAR in lowering GH and IGF-I concentrations in acromegalic patients. This treatment was also well tolerated by the patients, giving fewer local side-effects and technical problems with injections. These advantages may improve the long-term acceptability of medical treatment in acromegaly.

Acromegaly↗

Neurological involvement in a case of hypophosphatemia.

Hypophosphatemia occasionally underlies neurological disorders such as encephalopathy, myopathy and neuropathy. Although several cases have been reported in the literature, severe hypophosphatemia as a cause of neurological disorders is rarely mentioned in neurological textbooks and is seldom thought of in practice. We present a 69-year-old woman who develops encephalopathy and rapidly progressive weakness due to hypophosphatemia. The cause of hypophosphatemia is often iatrogenic and multifactorial. Signs and symptoms are mostly non-specific, thus complicating correct diagnosis and appropriate treatment.

Journal Article↗

Thyroid disorders in infertile women.

Thyroid hormones have profound effects on reproduction and pregnancy. There is a known association of hyper- and hypothyroidism with menstrual disturbances and decreased fecundity. Women with reproductive failure also have an increased prevalence of organ specific autoimmunity compared to fertile women. The present study aims to answer the following questions: 1) is there an increased prevalence of thyroid antibodies in infertile women? 2) are thyroid antibodies associated with a particular cause of infertility? and 3) do these antibodies influence outcome of the in vitro fertilization procedure? The answers to the two first questions were evaluated with a case-control study looking at the occurrence of thyroid autoimmunity and thyroid function tests among women of infertile couples (n=438), presenting for the first time at the department of reproductive medicine. For comparison, a control population of parous women (n=100), matched for age, was included. In 45% of the infertile couples a female cause of infertility was identified: endometriosis (11%), tubal disease (30%) and ovarian dysfunction (59%). Male infertility was diagnosed in 38% and idiopathic infertility in 17% of the couples. Mean serum TSH levels were significantly higher in patients with infertility compared with control patients: 1.6 +/- 2.6 versus 1.2 +/- 0.7 mIU/L. The proportion of positive TPO-Abs was higher in all women of infertile couples, compared with controls (14% versus 8%), but the difference was not significant. Considering only the female causes of infertility a significant higher proportion of women had positive TPO-Abs compared with controls (18% versus 8%), and in particular a high prevalence of thyroid autoimmunity was found in women suffering from endometriosis (29%). Both hypo- and hyperthyroidism were more frequent when TPO-Abs were positive, compared to women without thyroid autoimmunity. The results of the present study indicate that endometriosis, increases the relative risk for associated thyroid autoimmunity to 2.3, and therefore screening for thyroid auto-antibodies could be systematically proposed in these women.

Adult↗

Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene.

The calcium-sensing receptor (Ca-R) is a G-protein-coupled surface receptor that plays a crucial role in calcium homeostasis via parathyroid hormone secretion. Mutations of this receptor can cause a gain in, or loss of, function, leading to hypo- or hypercalcemia, respectively. We report here a family with hypocalcemia in whom a heterozygous missense mutation in exon 4 was demonstrated, predicting a proline to leucine substitution (P221L) in the extracellular part of the Ca-R. Clinical symptoms were limited to fatigue. When serum calcium was further lowered via a citrate infusion, a significant increase in circulating iPTH was observed, although with lower peak values than in normal controls, suggesting a gain in function of the Ca-R. Treatment with calcium supplements and calcitriol led to prohibitive hypercalciuria without normalizing serum calcium. The aims of this case report are: (1) to present a mutation in the Ca-R with a gain in function at a codon where previously loss of function was described, and (2) to suggest that measuring circulating iPTH during a citrate infusion in the presence of familial hypocalcemia is an additional test to diagnose this particular form of hypoparathyroidism.

Journal Article↗

A "bad responder" to statins.

We report the case of a man whose high-density lipoprotein cholesterol (HDL-C) and the ratios of total cholesterol to HDL-C and low-density lipoprotein cholesterol to HDL-C worsened dramatically during pravastatin treatment. After 3 years, pravastatin was replaced by fenofibrate. The result was spectacular. The HDL-C increased to at least twice the level obtained during pravastatin.

Anticholesteremic Agents↗

Thyroid and infertility.

Infertility is defined as the inability to conceive after one year of regular intercourse without contraception. The prevalence of infertility is estimated between 12 and 14% and remains stable in recent years. It thus represents a common condition, with important medical, economic and psychological implications. According to a standard protocol infertility evaluation usually identifies different causes, including, male infertility (30%), female infertility (35%), the combination of both (20%), and finally unexplained or "idiopathic" infertility (15%). Female causes of infertility comprise endometriosis, tubal damage and ovulatory dysfunction (OD). Thyroid dysfunction is a condition known to reduce the likelihood of pregnancy and to adversely affect pregnancy outcome. Data on the relationship between thyroid disorders and infertility remain scarce and the association with a particular cause of infertility has not thoroughly been analyzed. In a case-control study we have shown that the relative risk of positive TPO-Abs in infertility due to a female cause and in particular related to endometriosis is significantly increased. Thyroid dysfunction itself is a condition interfering with normal ovarian function and was more frequent in women with positive anti-TPO Abs. We therefore propose that a systematic screening of TSH, free T4 and TPO-Ab could be considered in all women with a female cause of infertility. Prospective follow-up of a cohort of infertile women undergoing assisted reproduction shows a significant increased risk of miscarriage in women with positive anti-TPO Abs compared to women without thyroid auto-immunity after clinical pregnancy is established by the ART procedure. The frequent association of the presence of anti-TPO-Abs and miscarriage is hypothetical explained by the fact that organ specific autoimmune diseases may be secondary to some basic cellular abnormality that directly affects pregnancy outcome. Alternatively, women with thyroid autoimmunity, may experience greater changes in free thyroxine levels during ART and subsequent pregnancy interfering with genital tract physiology and fetal development. Determining the presence of thyroid antibodies before ART procedure is thus useful in identifying women at risk for subsequent clinical miscarriage.

Abortion, Spontaneous↗

Non-secreting atypical parathyroid adenoma.

Parathyroid tumors can be divided in adenomas and carcinomas, usually detected by hypercalcemia. We report a case of parathyroid adenoma in a young man, who complained of a pressure in the left neck region. Physical examination revealed a firm mass in the neck, without lymphnodes. Although Ca (9.7 mg/dl), phosphorus (3.3 mg/dl) and intact-PTH (49 pg/ml) were normal, imaging techniques (computed tomography scan and sestamibi substraction scan) suggested that the mass could arise from the parathyroid gland. Histology and immune staining for chromogranin and parathyroid hormone confirmed the parathyroid nature of the mass. Histological criteria defined the lesion as an atypical parathyroid adenoma. We review the pathology, diagnosis and treatment of parathyroid adenomas in its non-secreting atypical form.

Adenoma↗

Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus.

Receptors for prolactin (PRL-R) are expressed in normal leukocytes from rat and man. PRL signals through PRL-R associated Janus tyrosine kinase (Jak)-2 and signal transducers and activators of transcription (Stat). In addition, in human leukocytes PRL also activates the p38 MAP kinase pathway. PRL, at physiological concentrations, stimulates the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the 'suppressors of cytokine signaling' (SOCS) family and inducible nitric oxide synthase (iNOS; in mononuclear cells and in granulocytes) and IRF-1 (in granulocytes). Thus, in normal leukocytes, PRL induces the expression of several genes relevant to innate and acquired immune responses. Sex hormones, such as estrogen and PRL, have been implicated in the pathogenesis of murine and human SLE. Also defective signaling in leukocytes is a feature of the disease. What the origin is of aberrant signaling processes in SLE lymphocytes and how they relate to tolerance breakdown and immunopathology is still unknown. It is not unlikely that PRL is a player at some level. The exact contribution of PRL to immune responses in normal subjects and in SLE patients is not known. Further work should also indicate whether PRL might contribute to the onset or progression of the disease and assess the possible benefits of manipulating PRL concentrations in patients.

Animals↗

Rapid detection of macroprolactin in the form of prolactin-immunoglobulin G complexes by immunoprecipitation with anti-human IgG-agarose.

Immunoprecipitation with anti-human immunoglobulin G-agarose was evaluated for the detection of prolactin-immunoglobulin G (PRL-IgG) complexes in macroprolactinemic samples from hyperprolactinemic patients (prolactin measured using the automated Elecsys PRL assay; Roche Diagnostics, Mannheim, Germany). Using the polyethylene glycol (PEG) precipitation test on serum samples with PRL above 1000 mIU/l, we detected macroprolactin in 38 out of 175 samples with a recovery below 50%. Gel filtration chromatography on a subset of hyperprolactinemic samples confirmed that macroprolactin was the predominant immunoreactive form of PRL in samples which showed a recovery < or = 50%. In 37 out of 38 samples containing macroprolactin, immunoprecipitation with anti-human IgG (anti-hIgG)-agarose revealed a higher PRL-binding (19.1-91.3%) than in the sera containing monomeric PRL (< 10%). In conclusion, we found that PEG precipitation detected macroprolactin in 21.7% of samples with elevated PRL levels as measured by the Elecsys PRL assay, and that in the vast majority of these samples the presence of PRL-IgG complexes could be demonstrated by immunoprecipitation with anti-hIgG-agarose. In view of the high prevalence of PRL-IgG complexes in hyperprolactinemic patients and the simplicity of the test, immunoprecipitation with anti-hIgG-agarose might play a role in the routine laboratory handling of hyperprolactinemic samples, especially with regards to PRL assays where PEG causes interference.

Antigen-Antibody Complex↗

From prolactin cell to prolactinoma.

The pathogenesis, diagnosis and treatment of common pituitary neoplasms is based on the understanding of the differentiated hormone expression by specific pituitary cell types and of the central hypothalamic, peripheral and local control of their hormonal secretion (endocrine, autocrine, paracrine regulation). Tumorigenesis is the result of a complex multistep process. It is likely that a molecular genetic alteration initially leads to cell transformation. Nevertheless the transformed cell is dependent on hormonal and/or growth factor stimulation for tumor progression. This cascade is responsible for autonomic hormone secretion, and cell proliferation. PRL cells do not behave identically in terms of cell function. Functional diversity among PRL cells is documented in vitro, in terms of basal and synthetic capacity and in respect to responsiveness to dopamine and oestrogen regulation. These in vitro observations can be extended to the in vivo situation. In the intact pituitary, PRL cells differ in their relative content of PRL and their response to secretagogues. These differences relate to their topographical localization within the pituitary. Prolactinoma are mainly composed of cells with a high basal synthetic and secretory capacity and arise preferentially in the peripheral parts of the hypophysis. It is therefore tempting to postulate that the "in situ milieu" within the pituitary is relevant for the development of prolactinoma. By stimulating growth in certain areas, there is an increased probability of mutation. At the same time growth of a mutated PRL cell could be stimulated.

Cell Division↗

Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines.

To evaluate the possible role of the recently described family of suppressors of cytokine signaling (SOCS) factors in the human lympho-hemopoietic system, we have monitored SOCS factor expression, both constitutive and induced by either cytokines, prolactin (PRL) or growth hormone (GH), using polymerase chain reaction in normal and leukemic cells. CIS (cytokine-inducible SH2-containing protein), SOCS-2 and SOCS-3 were constitutively expressed in peripheral blood mononuclear leukocytes. SOCS-3 expression was enhanced by PRL or by IFN-gamma. In bone marrow cells and granulocytes, CIS expression was induced and SOCS-2 enhanced by IFN-gamma and by PRL. In tonsillar cells, CIS expression was increased and SOCS-2 was induced by IL-1beta, IL-6, PRL and GH. SOCS-3 expression was enhanced by IL-1beta. The expression of SOCS-7 was increased by IL-6, PRL and GH. In Raji B-lymphoma cells, the expression of SOCS-2 and SOCS-7 was enhanced by IL-1beta. In THP-1 myeloid leukemia cells pretreated with TPA (to induce receptors for IFN-gamma), IFN-gamma induced SOCS-2. Jurkat cells expressed more SOCS-2 when exposed to PRL. Original observations in this work include the first report on SOCS-7 induction by cytokines. Also our data shed new light on the possible involvement of PRL and GH in the cytokine network. These hormones could modulate the transduction of signals originating from receptors for various cytokines.

Cell Line↗