Biomedical subjects

K Boer

Publications and source records attributed to K Boer.

At least 19 recordsLinked to original sources

PubMed2007

Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development.

Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the mechanisms of hyperexcitability that lead to seizures. In the present study the expression and cell-specific distribution of Na+-K+-2Cl--cotransporter (NKCC1) and K+-Cl--cotransporter (KCC2) were studied immunocytochemically in different developmental lesions, including focal cortical dysplasia (FCD) type IIB (n=9), hemimegalencephaly (HMEG, n=6) and ganglioglioma (GG, n=9) from patients with medically intractable epilepsy and in age-matched controls. In normal control adult cortex, NKCC1 displayed low neuronal and glial expression levels. In contrast KCC2 showed strong and diffuse neuropil staining. Notable glial immunoreactivity (IR) was not found for KCC2. NKCC1 was highly expressed in the majority of FCD, HMEG and GG specimens. NKCC1 IR was observed in neurons of different size, including large dysplastic neurons, in balloon cells (in FCD and HMEG cases) and in glial cells with astrocytic morphology. The immunoreactivity pattern of KCC2 in FCD, HMEG and GG specimens was characterized by less neuropil staining and more intrasomatic IR compared with control. KCC2 IR was observed in neurons of different size, including large dysplastic neurons, but not in balloon cells or in glial cells with astrocytic morphology. Double-labeling experiments confirmed the differential cellular distribution of the two CCTs and their expression in GABA(A) receptor (alpha1 subunit)-positive dysplastic neurons. The cellular distribution of CCTs, with high expression of NKCC1 in dysplastic neurons and altered subcellular distribution of KCC2 resembles that of immature cortex and suggests a possible contribution of CCTs to the high epileptogenicity of malformations of cortical development.

Adolescent↗

PubMed2006

Reproduction and fertility in human immunodeficiency virus type-1 infection.

Human immunodeficiency virus type-1 (HIV-1) affects mostly men and women in their reproductive years. For those who have access to highly active antiretroviral therapy (HAART), the course of HIV-1 infection has shifted from a lethal to a chronic disease. As a result of this, many patients with HIV-1 consider having offspring, as do other patients of reproductive age with chronic illnesses. This article summarizes the current knowledge on the presence of HIV in the male and female genital tract, the effects of HIV-1 infection and HAART on male and female fertility and the results of various assisted reproduction techniques (ART) in HIV-1-infected men and women who wish to have offspring.

Anti-HIV Agents↗

PubMed2006

The IL-1beta system in epilepsy-associated malformations of cortical development.

Focal cortical dysplasia (FCD) and glioneuronal tumors (GNT) are recognized causes of chronic intractable epilepsy. The cellular mechanism(s) underlying their epileptogenicity remain largely unknown. Compelling evidence in experimental models of seizures indicates an important role of interleukin (IL)-1beta in the mechanisms of hyperexcitability leading to the occurrence of seizures. We immunocytochemically investigated the brain expression and cellular distribution pattern of IL-1beta, IL-1 receptor (IL-1R) types I and II and IL-1R antagonist (IL-1Ra) in FCD and GNT specimens, and we correlate these parameters with the clinical history of epilepsy in patients with medically intractable seizures. In normal control cortex, and in perilesional regions with histologically normal cortex, IL-1beta, IL-1Rs and IL-1Ra expression was undetectable. In all FCD and GNT specimens, IL-1beta and its signalling receptor IL-1RI were highly expressed by more than 30% of neurons and glia whereas the decoy receptor IL-RII and IL-Ra were expressed to a lesser extent by approximately 10% and 20% of cells, respectively. These findings show a high expression of IL-1beta and its functional receptor (IL-1RI) in FCD and GNT specimens together with a relative paucity of mechanisms (IL-1RII and IL-1Ra) apt to inactivate IL-1beta actions. Moreover, the number of IL-1beta- and IL-1RI-positive neurons was positively correlated with the frequency of seizures, whereas the number of IL-1Ra-positive neurons and astroglial cells was negatively correlated with the duration of epilepsy prior to surgery. The expression of IL-1beta family members in these developmental lesions may contribute to their intrinsic and high epileptogenicity, thus possibly representing a novel target for antiepileptic strategies.

Adolescent↗

PubMed2006

Evidence of activated microglia in focal cortical dysplasia.

Focal cortical dysplasia (FCD), which is caused by malformations of cortical development, is known to be a major cause of intractable epilepsy. Cortical laminar disorganization and the presence of abnormal neuronal and astroglial cell types are histological characteristics of FCD. Though, little information is known about the microglia/macrophage cell system in FCD and its possible contribution to the high epileptogenesis of this disorder. In the present study, the distribution of cells of the microglia/macrophage lineage was studied in 20 specimens of FCD (type II) by immunocytochemistry for CD68 and human HLA-DR. A significant number of microglial cells and macrophages were observed within the dysplastic cortex. The mean number of CD68- and HLA-DR-positive cells was significantly higher in FCD specimens than in normal-appearing control cortex obtained at autopsy. HLA-DR-positive cells, which represent activated microglia, were localized around blood vessels and also clustered around dysplastic neuronal cells. The density of these activated HLA-DR-positive microglial cells correlated with the duration of epilepsy, as well as with the frequency of seizures prior to surgical resection. CD68-positive macrophages were mainly located around vessels and the number of these cells did not correlate with seizure frequency, neither with the duration of symptoms prior to surgical resection. In conclusion, our findings demonstrate a specific and persistent increase in the numerical density of HLA-DR-positive activated microglia within the dysplastic region, supporting the contribution of the inflammatory response and proinflammatory molecules to the epileptogenicity of FCD.

Adolescent↗

PubMed2006

Serial analysis of gene expression in the hippocampus of patients with mesial temporal lobe epilepsy.

Hippocampal sclerosis constitutes the most frequent neuropathological finding in patients with medically intractable mesial temporal lobe epilepsy. Serial analysis of gene expression was used to get a global view of the gene profile in human hippocampus in control condition and in epileptic condition associated with hippocampal sclerosis. Libraries were generated from control hippocampus, obtained by rapid autopsy, and from hippocampal surgical specimens of patients with mesial temporal lobe epilepsy and the classical pattern of hippocampal sclerosis. More than 50,000 tags were analyzed (28,282, control hippocampus; 25,953, hippocampal sclerosis) resulting in 9206 (control hippocampus) and 9599 (hippocampal sclerosis) unique tags (genes), each representing a specific mRNA transcript. Comparison of the two libraries resulted in the identification of 143 transcripts that were differentially expressed. These genes belong to a variety of functional classes, including basic metabolism, transcription regulation, protein synthesis and degradation, signal transduction, structural proteins, regeneration and synaptic plasticity and genes of unknown identity of function. The database generated by this study provides an extensive inventory of genes expressed in human control hippocampus, identifies new high-abundant genes associated with altered hippocampal morphology in patients with mesial temporal lobe epilepsy and serves as a reference for future studies aimed at detecting hippocampal transcriptional responses under various pathological conditions.

Base Sequence↗

PubMed2006

Histological classification of chorionic villous vascularization in early pregnancy.

BACKGROUND: The objective of the study was to assess the reproducibility of a new classification for early pregnancy chorionic villous vascularization (Grade: I, normal; IIA, mild hypoplasia; IIB, severe hypoplasia and III, avascular) for routine microscopic examination in daily clinical practice. METHODS: In this observational study, four observers scored first trimester chorionic villous vascularization. Scoring was performed in microscopic slides of chorionic tissue obtained by D&C in 30 patients with early pregnancy loss due to empty sac (n = 10), fetal death (n = 10) and termination of pregnancy (n = 10) using the new classification. Ultrasonographic measurement of trophoblastic thickness (TT) at the implantation site was available in all patients and in a reference group of 100 ongoing singleton pregnancies. The vascularization score could therefore be related to the TT. RESULTS: The new classification resulted in a good-to-excellent agreement in histological scoring (0.73-0.90) between investigators (kappa 0.64-0.86). TT was not related to either vascularization or pregnancy outcome and only partly to hydropic degeneration. CONCLUSION: The vascularization scoring system is a simple, valid and effective method for assessment of chorionic villous vascularization. It is helpful in understanding the underlying cause of pregnancy loss, as the classification can distinguish between normal and abnormal embryonic development. We did not find either a relation between TT and pregnancy outcome or between TT and vascularization.

Adult↗

PubMed2006

Hypercalcitoninemia in a patient with a recurrent goitre and insulinoma: a case report.

Serum calcitonin has become a very sensitive and specific marker for medullary thyroid carcinoma that should be determined in patients with nodular thyroid disease. However, a few earlier reports indicated that tumors other than medullary thyroid carcinoma including insulinomas arising from pancreatic islet cells may also produce calcitonin. Of the few cases of calcitonin-producing insulinomas previously reported, most had incomplete data or lack of documentation of the association between raised serum calcitonin concentration and immunohistochemical detection of calcitonin in pancreatic islet cell tumors. In this paper we are reporting a 54-year-old woman with a history of partial thyroidectomy for multinodular goitre at the age of 50 yrs, she was evaluated for a 2-months history of fasting hypoglycemia (plasma glucose 1.9 mmol/L during a supervised fast), raised serum insulin (at the time of hypoglycemia 88.8 microU/ml; normal, 5 - 35 microU/ml) and C-peptide levels (at the time of hypoglycemia 6.1 ng/ml; normal, 1.37 - 3.51 ng/ml), markedly increased serum calcitonin concentration (481 pg/ml; normal, < 9.9 pg/ml), and an enlarged residual thyroid gland. Aspiration biopsy of the thyroid was negative for parafollicular C-cell hyperplasia or medullary thyroid carcinoma. Abdominal ultrasound and CT scan revealed a tumor in the head of the pancreas, which was surgically removed. Histopathological evaluation of the pancreatic tumor showed typical features of a neuroendocrine neoplasm with strong immunostaining for both insulin and calcitonin. After removal of the pancreatic tumor, clinical symptoms resolved and biochemical markers normalized (serum insulin, 14.9 microU/ml; C-peptide, 3.0 ng/ml; calcitonin, 2.9 pg/ml) confirming the causal relationship between insulinoma and markedly increased serum calcitonin levels.

Calcitonin↗

PubMed2005

Vasculogenesis in complete and partial hydatidiform mole pregnancies studied with CD34 immunohistochemistry.

BACKGROUND: Defective chorionic villous vascularization is present in pregnancies complicated by absent or abnormal embryonic development. The aim of this study was to investigate the embryonic and/or maternal genomic influence on vasculogenesis in diploid complete hydatidiform mole (CHM) and in triploid partial hydatidiform mole (PHM) in comparison with normal development. METHODS: Mean villous stromal area and functional vascular area, vessels with a lumen and haemangiogenetic cords, peripherally or centrally located were measured and counted in chorionic villi of 12 CHM, 12 normal pregnancies (termination of pregnancy, TOP) and 15 PHM of which nine were without an embryo (PHM-E) and six were with an embryo (PHM + E), using quantitative CD34 immunohistochemistry. RESULTS: TOP showed significantly more vessels per chorionic villus, centrally and peripherally located (median, range), than CHM, PHM-E and PHM + E (4.0, 0-9 versus 0.0, 0-11, 0.0, 0-18 and 1.0, 0-21). CHM showed significantly more centrally located cords than PHM-E, PHM + E and TOP (1.5, 0-22 versus 1.0, 0-15, 0.5, 0-8 and 1.0, 0-2). CONCLUSIONS: Initiation of chorionic villous vasculogenesis is independent of the maternal genome (CHM). The development of an embryo, however, is obligatory for the modulation of normal vascularization resulting in a well developed vasculosyncytial membrane.

Adult↗

PubMed2004

[Treatment of HIV-1 infected pregnant women].

Since 1 January 2004, pregnant women in the Netherlands have been universally screened for HIV infection. Three HIV-infected, pregnant women aged 28, 24 and 33 years respectively, illustrate some of the problems that may be encountered in this situation, as well as the treatment options available to prevent the transmission of HIV from mother to child. The first patient had a positive antibody test early in pregnancy for which she did not need treatment, the second had a positive antibody test late in pregnancy and the third was seropositive and on medication, but had the wish to become pregnant. A vaginal delivery is possible when highly active antiretroviral therapy (HAART) of the mother is started in good time and the plasma HIV-RNA is < 400 copies/ml at the time of delivery. In this situation the risk of transmission is reduced to around 1%. However, if HIV infection is diagnosed late in pregnancy or, despite HAART, the plasma HIV-RNA is not expected to be < 400 copies/ml, an elective caesarean section is scheduled at 38 weeks of pregnancy. In all instances the neonate is treated for 28 days with antiretrovirals, as post-exposure prophylaxis. If a woman with a known HIV infection wants to become pregnant, the choice of antiretroviral regimen and when this is started is determined by her treatment history and the potential toxic effects of the medication on the foetus.

Adult↗

PubMed2004

[Highly active antiretroviral therapy (HAART) in HIV-positive pregnant women in the Netherlands, 1997-2003: safe, effective and with few side effects].

OBJECTIVE: To assess the side effects, safety and efficacy of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected pregnant women in the Netherlands. DESIGN: Retrospective. METHOD: Data were collected from the medical records of HIV-infected pregnant women who received HAART during pregnancy in the period 1 January 1997-1 June 2003 at 14 HIV-specialized centres in the Netherlands. The inclusion criteria were at least a triple drug regimen and birth at 20 or more weeks of gestation. Information was collected about patient characteristics, HAART prescribed, side effects, viral load response, mode of delivery and HIV-status of the neonate. RESULTS: A total of 267/413 women satisfied the inclusion criteria. Most women (n = 199) had not previously received anti-retroviral therapy and started HAART between weeks 21 and 28 of the pregnancy. The two most frequently used regimens contained nelfinavir (57%) or nevirapine (31%). Gastrointestinal side effects were more frequently observed in the nelfinavir group, while rash and hepatotoxicity were more frequently reported in the nevirapine group. Efficacy and pregnancy outcome were similar in both groups. Two infants (0.7%) were HIV-infected. CONCLUSION: HAART regimens containing nelfinavir or nevirapine in HIV-infected pregnant women were safe, effective and well tolerated.

Adolescent↗

PubMed2004

[Less refusal to participate in HIV screening among pregnant women in the Amsterdam region since the introduction of standard HIV screening using the opting-out method].

In 2003 the Municipal Health Service in Amsterdam started to screen pregnant women for HIV according to the opting-out method. In this method the HIV test is routinely included in the prenatal screening along with hepatitis B virus (HBV) and syphilis. If the woman does not want to be tested for HIV then she must actively opt out of this test. This screening method was chosen because in the universal screening method used in 2002, women had to give their explicit consent to test for HIV and this led to a high refusal rate (13.6%), especially among women from AIDS-endemic countries. After the introduction of the opting-out method, the refusal rate fell from 3% in the first quarter of 2003 to 1.4% in the last quarter of 2003. None of the women refused to be tested for HBV or syphilis. In 2003, the HIV prevalence among pregnant women was 0.3% (35/13.621). The experiences with this screening method in Amsterdam were used to implement the national opting-out method for HIV screening in pregnant women, which was introduced on 1 January 2004.

Adolescent↗

PubMed2004

Determination of sixteen UV filters in suncare formulations by high-performance liquid chromatography.

Reversed-phase liquid chromatography (RP-LC) with UV detection was developed for the simultaneous determination of 16 organic UV filters worldwide authorized in suncare products. The filters determined were: 4-aminobenzoic acid, homosalate, benzophenone-3,2-phenylbenzimidazole-5-sulfonic acid, terephthalidene dicamphor sulfonic acid, 4-tert-butyl-4'-methoxy-dibenzoylmethane, octocrylene, 2-ethylhexyl-4-methoxycinnamate, isoamyl-p-methoxycinnamate, ethylhexyltriazone, drometrizole trisiloxane, diethylhexyl butamido triazone, 3-(4-methylbenzyliden) camphor, 2-ethylhexylsalicylate, 2-ethylhexyl-4-dimethylaminobenzoate and benzophenone-4. A C18 stationary phase and a gradient of ethanol-aqueous acetate buffer containing 0.2 mM of EDTA, was used with a flow-rate of 1.0 ml/min. UV detection was carried out at 313 and 360 nm. The analysis required 32 min and the limits of detection were between 30 and 4130 mg/kg in the original suncare product. Tween 80 was used to break down the different emulsions in order to procure a proper extraction of the UV filters. The method was validated for UV filters in three matrices, oil, water-in-oil emulsion and oil-in-water emulsion. Recoveries from spiked samples were 86-113% depending on the matrix used.

Chemistry, Pharmaceutical↗

PubMed2003

[HIV-screening among pregnant women in the region of Amsterdam in 2002].

In 2001, the Municipal Health Service started offering HIV tests to all pregnant women in and around Amsterdam. All midwives and all hospitals but one participated in this HIV screening. In 2002, of the 10,752 pregnant women offered HIV testing 13.6% refused. HIV antibodies were detected in 24 women (0.26%). The HIV prevalence was doubled compared to the prevalence in 1990-1991, but the number of newly HIV-infected pregnant women remained stable (0.1%). The high number of refusals, as a result of which many HIV-infected women might be missed, is alarming. For this reason, in January 2003, the Municipal Health Service started HIV testing by the opting-out approach. Under the opting-out approach, women are notified that an HIV test will be included in the standard test battery, together with tests for hepatitis B and syphilis, unless she explicitly refuses. It is expected that the opting-out approach for HIV screening of pregnant women will be implemented nationwide in 2003.

Adult↗

PubMed2003

High activity of fatty acid oxidation enzymes in human placenta: implications for fetal-maternal disease.

As the human fetus and placenta are considered to be primarily dependent on glucose oxidation for energy metabolism, the cause of the remarkable association between severe maternal pregnancy complications and the carriage of a fetus with an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) has remained obscure. We analysed human term placenta and chorionic villus samples for the activities of a variety of enzymes involved in FAO, and compared the results with those obtained in human liver. All enzymes were found to be expressed, with a very high activity of two enzymes involved in the metabolism of long-chain fatty acids (CPT2 and VLCAD), whereas the activity of medium-chain acyl-CoA dehydrogenase (MCAD) was found to be low, when compared to liver. These results suggest that fatty acid oxidation may play an important role in energy generation in human placenta, and that a deficiency in the placental oxidation of long-chain FAO may result in placental dysfunction, thus causing gestational complications.

Acyl-CoA Dehydrogenase↗

PubMed2001

[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child].

Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid whilst on levothyroxine treatment. Two women had previously received 131iodine therapy due to Graves' disease. During pregnancy the levothyroxine dose required to maintain a normal TSH level increased. The serum TSH-binding inhibiting immunoglobulins (TBII) activity was still very high (188 U/l) in one of the women, but decreased to 26 U/l in the last trimester. Foetal or neonatal thyrotoxicosis was not observed. The levothyroxine dose was decreased after delivery and none of the women experienced any adverse effects as a result of this. It is recommended that all women taking levothyroxine should have their serum TSH activity measured during the first trimester. The daily dose of levothyroxine required will usually increase by 50 micrograms during pregnancy. The determination of serum TBII activity is indicated in the case of Graves' disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal thyrotoxicosis.

Adult↗

PubMed2001

[Pregnancy (conception) in hyper- or hypothyroidism].

Pregnancy is accompanied by changes in thyroid function. Due to the increased synthesis of thyroid binding globulin and the thyroid-stimulating effect of human chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will increase in the first trimester of pregnancy (total T4, T3). Free T4 levels decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is usually due to Graves' disease. Definitive therapy may be considered for cases prior to pregnancy, although a medical management as would be given during pregnancy is an equally good option. The medical management of hyperthyroidism consists of a monotherapy with thyreostatics in which the recommended dose needs to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating hormone (TSH) in the low-normal area so as to minimise the risk of foetal hypothyroidism. The transplacental passage of maternal TSH receptor stimulating antibodies may cause foetal hyperthyroidism. Another cause of maternal hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which is associated with high hCG levels during the first trimester of pregnancy. It is nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy has negative consequences for the foetus. If the hypothyroidism is apparent prior to pregnancy, it should be corrected before conception (target TSH value of 1 mU/l). If discovered during pregnancy, treatment with levothyroxine should be started as soon as possible. In the case of a pre-existing hypothyroidism a 25-50% increase in the levothyroxine dosage is often needed during the first trimester of pregnancy. This is possibly due to an increased requirement. An adequate serum concentration of T4 is necessary for foetal brain development.

Adult↗

PubMed2001

Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders.

BACKGROUND: Animal studies demonstrated that early exposure to phenobarbital decreases reproductive function. This study investigates whether prenatal exposure to these anticonvulsants affects human genital tract development. METHODS: Genital anomalies at birth were studied retrospectively in 90 phenobarbital-exposed, 108 phenobarbital plus phenytoin-exposed, and 198 matched control infants. Of this group, 72 drug-exposed males, 75 drug-exposed females, and 147 matched control subjects participated in a follow-up and were interviewed at age 19-35. Differences between groups were tested by chi-square and t-tests. RESULTS: A total of 15% of the phenobarbital-exposed boys versus 2.8% control boys had undescended testes at birth. More anticonvulsant-exposed (24%) than control males (11%) had received medical treatment for genital anomalies. Anticonvulsant-exposed females more often had irregularities in menstrual cycles (31% vs. 17%) and bleeding (15% vs. 3%) and reported more problems during pregnancy. CONCLUSIONS: Prenatal exposure to anticonvulsants seems to induce minor genital anomalies and may affect reproductive function.

Adult↗

PubMed2001

In vitro placental pressure-flow behaviour is non-linear and depends on the external pressure.

OBJECTIVE: To study pressure-flow behaviour of in vitro placentas under normal simulated conditions and during raised external pressures, to simulate in vivo placental hemodynamic function, and as a model for polyhydramnios and the supine hypotension syndrome. DESIGN: Eleven normal term human singleton in vitro placentas were perfused under optimal physiologic conditions. Perfusion pressures varied between 5 and 90 mmHg, external pressures between 4 and 30 mmHg. Venous-external pressure (mmHg) combinations included 10-4, 10-10, 20-20, 25-25, 30-30 and 10-20. RESULTS: Pressure-flow curves varied markedly among the 11 placentas, but all showed a non-linear, perfusion pressure-dependent resistance. The in vitro placental resistances were significantly higher than estimated in vivo values. All placentas showed inevitable leakage at the maternal side due to damage during delivery. Increased external pressures increased the placental resistance at lower perfusion pressures. CONCLUSION: Placental damage reduces the number of perfused cotyledonic capillaries. This increases the placental resistance but preserves circulatory properties. Our findings therefore, represent in vivo placental function. They may explain why polyhydramnios often persists and that polyhydramnios and the supine hypotension syndrome are likely to be more detrimental in hypotensive than in normotensive or hypertensive fetuses.

Adult↗