37 results on '"Boer, L. de"'
Search Results
2. Clinical and biochemical footprints of inherited metabolic diseases. XII. Immunological defects.
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Boer, L. de, Cambi, A., Verhagen, L.M., Haas, P. de, Karnebeek, C.D. van, Blau, N., Ferreira, C.R., Boer, L. de, Cambi, A., Verhagen, L.M., Haas, P. de, Karnebeek, C.D. van, Blau, N., and Ferreira, C.R.
- Abstract
Item does not contain fulltext, Immunological problems are increasingly acknowledged manifestations in many inherited metabolic diseases (IMDs), ranging from exaggerated inflammation, autoimmunity and abnormal cell counts to recurrent microbial infections. A subgroup of IMDs, the congenital disorders of glycosylation (CDG), includes CDG types that are even classified as primary immunodeficiencies. Here, we reviewed the list of metabolic disorders reported to be associated with various immunological defects and identified 171 IMDs accompanied by immunological manifestations. Most IMDs are accompanied by immune dysfunctions of which immunodeficiency and infections, innate immune defects, and autoimmunity are the most common abnormalities reported in 144/171 (84%), 44/171 (26%) and 33/171 (19%) of IMDs with immune system involvement, respectively, followed by autoinflammation 17/171 (10%). This article belongs to a series aiming at creating and maintaining a comprehensive list of clinical and metabolic differential diagnoses according to organ system involvement.
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- 2023
3. Oral sialic acid supplementation in NANS-CDG: Results of a single center, open-label, observational pilot study.
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Hollander, B. den, Brands, M.M., Boer, L. de, Haaxma, C.A., Lengyel, A., Essen, P. van, Peters, G.T.M., Kwast, H.J.T., Klein, W.M., Coene, K.L.M., Lefeber, D.J., Karnebeek, C.D.M. van, Hollander, B. den, Brands, M.M., Boer, L. de, Haaxma, C.A., Lengyel, A., Essen, P. van, Peters, G.T.M., Kwast, H.J.T., Klein, W.M., Coene, K.L.M., Lefeber, D.J., and Karnebeek, C.D.M. van
- Abstract
01 september 2023, Contains fulltext : 296342.pdf (Publisher’s version ) (Open Access), NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0-28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.
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- 2023
4. Using PRPP-Assessment for measuring change in everyday activities by home-based videos: An exploratory case series study in children with multiple disabilities.
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Rothuizen-Lindenschot, M., Graff, M.J.L., Boer, L. de, Groot, I.J.M. de, Nijhuis-van der Sanden, M.W.G., Steultjens, E.M.J., Koene, S., Rothuizen-Lindenschot, M., Graff, M.J.L., Boer, L. de, Groot, I.J.M. de, Nijhuis-van der Sanden, M.W.G., Steultjens, E.M.J., and Koene, S.
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Contains fulltext : 300242.pdf (Publisher’s version ) (Open Access), BACKGROUND: Currently, paediatric health care aims to use a child-centred tailor-made approach. In order to design tailored occupational therapy, the implementation of personalised occupation-based measurements that guide and evaluate goal setting and are responsive to change is necessary. PURPOSE: Primarily, this study explored the potential of the Perceive, Recall, Plan, and Perform (PRPP) assessment to measure the change in the performance of children with multiple disabilities. As a secondary evaluation, the feasibility of the PRPP-Intervention in a home-based program to enable activities was described. The overall aim is to show the potential of the PRPP-Assessment as an outcome measure to use as a base for designing tailor-made person-centred care. METHODS: An exploratory longitudinal multiple case series mixed-methods design was used. The PRPP-Assessment, scored by multiple raters, was conducted based on parent-provided videos. The assessed activities were chosen by the child and/or parents. Responsiveness was evaluated by hypotheses formulated a priori and by comparing measured change with change on concurrent measures: Goal Attainment Scaling (GAS) and Canadian Occupational Performance Measure (COPM). Over a 6-week period, children and their parents (or caregivers) participated in an online home-based video coaching program where parents were coached in the implementation of the training, based on the PRPP-Intervention, by paediatric occupational therapists on a weekly basis. The feasibility of the intervention was explored using semi-structured interviews with children, parents, and the treating occupational therapists and was analysed by directed content analysis. RESULTS: Three out of 17 eligible children agreed to participate and completed post-intervention measurement, of which two completed the intervention. Quantitative results showed that eight out of nine activities improved on the PRPP-Assessment and the COPM, and nine improved on the GAS. In tota, 01 december 2023
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- 2023
5. A randomised placebo-controlled, double-blind phase II study to explore the safety, efficacy, and pharmacokinetics of sonlicromanol in children with genetically confirmed mitochondrial disease and motor symptoms ('KHENERGYC')
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Smeitink, J.A., Maanen, Rob van, Boer, L. de, Ruiterkamp, G., Renkema, H., Smeitink, J.A., Maanen, Rob van, Boer, L. de, Ruiterkamp, G., and Renkema, H.
- Abstract
Contains fulltext : 249714.pdf (Publisher’s version ) (Open Access)
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- 2022
6. Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography
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Veenvliet, Annemarijne R.J., Garrelfs, M.R., Udink ten Cate, F.E.A., Ferdinandusse, S., Denis, Simone, Fuchs, Sabine A., Geurtzen, R., Wegberg, A.M.J. van, Huigen, M.C.D.G., Kluijtmans, L.A.J., Wanders, Ronald J.A., Derks, Terry G.J., Boer, L. de, Houtkooper, Riekelt H., Vries, M.C. de, Karnebeek, C.D. van, Veenvliet, Annemarijne R.J., Garrelfs, M.R., Udink ten Cate, F.E.A., Ferdinandusse, S., Denis, Simone, Fuchs, Sabine A., Geurtzen, R., Wegberg, A.M.J. van, Huigen, M.C.D.G., Kluijtmans, L.A.J., Wanders, Ronald J.A., Derks, Terry G.J., Boer, L. de, Houtkooper, Riekelt H., Vries, M.C. de, and Karnebeek, C.D. van
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Item does not contain fulltext
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- 2022
7. Evaluation of Cell Models to Study Monocyte Functions in PMM2 Congenital Disorders of Glycosylation
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Haas, P. de, Jonge, M.I. de, Koenen, H.J.P.M., Joosten, B.H., Janssen, M.C.H., Boer, L. de, Hendriks, W.J.A.J., Lefeber, D.J., Cambi, A., Haas, P. de, Jonge, M.I. de, Koenen, H.J.P.M., Joosten, B.H., Janssen, M.C.H., Boer, L. de, Hendriks, W.J.A.J., Lefeber, D.J., and Cambi, A.
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Item does not contain fulltext
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- 2022
8. Cognitive functioning and mental health in children with a primary mitochondrial disease
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Loo, K.F.E. van de, Custers, J.A.E., Boer, L. de, Lieshout, Marloes van, Vries, M.C. de, Janssen, M.C.H., Verhaak, C.M., Loo, K.F.E. van de, Custers, J.A.E., Boer, L. de, Lieshout, Marloes van, Vries, M.C. de, Janssen, M.C.H., and Verhaak, C.M.
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Contains fulltext : 283063.pdf (Publisher’s version ) (Open Access)
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- 2022
9. Synergistic use of glycomics and single-molecule molecular inversion probes for identification of congenital disorders of glycosylation type-1
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AbuBakar, N. Bin, Ashikov, A.M., Brum, J.M., Smeets, R.J.P., Kersten, Marjan, Huijben, Karin, Keng, W.T., Speck-Martins, C.E., Carvalho, D.R., Rizzo, I. de, Mello, W.D. de, Heiner-Fokkema, R., Gorman, K., Grunewald, S., Michelakakis, H., Moraitou, M., Martinelli, D., Scherpenzeel, M. van, Janssen, M.C.H., Boer, L. de, Heuvel, L.P.W.J. van den, Thiel, C, Lefeber, D.J., AbuBakar, N. Bin, Ashikov, A.M., Brum, J.M., Smeets, R.J.P., Kersten, Marjan, Huijben, Karin, Keng, W.T., Speck-Martins, C.E., Carvalho, D.R., Rizzo, I. de, Mello, W.D. de, Heiner-Fokkema, R., Gorman, K., Grunewald, S., Michelakakis, H., Moraitou, M., Martinelli, D., Scherpenzeel, M. van, Janssen, M.C.H., Boer, L. de, Heuvel, L.P.W.J. van den, Thiel, C, and Lefeber, D.J.
- Abstract
Contains fulltext : 282651.pdf (Publisher’s version ) (Open Access), Congenital disorders of glycosylation type 1 (CDG-I) comprise a group of 27 genetic defects with heterogeneous multisystem phenotype, mostly presenting with nonspecific neurological symptoms. The biochemical hallmark of CDG-I is a partial absence of complete N-glycans on transferrin. However, recent findings of a diagnostic N-tetrasaccharide for ALG1-CDG and increased high-mannose N-glycans for a few other CDG suggested the potential of glycan structural analysis for CDG-I gene discovery. We analyzed the relative abundance of total plasma N-glycans by high resolution quadrupole time-of-flight mass spectrometry in a large cohort of 111 CDG-I patients with known (n = 75) or unsolved (n = 36) genetic cause. We designed single-molecule molecular inversion probes (smMIPs) for sequencing of CDG-I candidate genes on the basis of specific N-glycan signatures. Glycomics profiling in patients with known defects revealed novel features such as the N-tetrasaccharide in ALG2-CDG patients and a novel fucosylated N-pentasaccharide as specific glycomarker for ALG1-CDG. Moreover, group-specific high-mannose N-glycan signatures were found in ALG3-, ALG9-, ALG11-, ALG12-, RFT1-, SRD5A3-, DOLK-, DPM1-, DPM3-, MPDU1-, ALG13-CDG, and hereditary fructose intolerance. Further differential analysis revealed high-mannose profiles, characteristic for ALG12- and ALG9-CDG. Prediction of candidate genes by glycomics profiling in 36 patients with thus far unsolved CDG-I and subsequent smMIPs sequencing led to a yield of solved cases of 78% (28/36). Combined plasma glycomics profiling and targeted smMIPs sequencing of candidate genes is a powerful approach to identify causative mutations in CDG-I patient cohorts.
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- 2022
10. Op zoek naar gevaarlijke stoffen in oppervlaktewater
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Smit, E., Wassenaar, P., Boer, L. de, Janssen, N., Smit, E., Wassenaar, P., Boer, L. de, and Janssen, N.
- Abstract
Nederland heeft van ruim 1.700 chemische stoffen vastgesteld dat ze gevaarlijk zijn voor mens en milieu, en beperkt de emissie van deze stoffen zo veel mogelijk. Daarnaast houdt het RIVM een lijst van verdachte stoffen bij, de ‘potentieel zeer zorgwekkende stoffen’ (pZZS). Ook is er nu een ‘similarity tool’ om verdachte stofgroepen te identificeren. Vergelijking met landelijke waterdata leerde dat zowel de pZZSlijst als de similarity tool nu al waardevol kunnen zijn voor waterbeheerders. Daarnaast kan de tool belangrijk worden voor een groepsgewijze aanpak van chemische stoffen (denk aan PFAS).
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- 2022
11. NANS-CDG: Delineation of the Genetic, Biochemical, and Clinical Spectrum
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Hollander, Bibiche den, Rasing, Anne, Post, M.A., Klein, W.M., Oud, M.M., Brands, Marion M., Boer, L. de, Engelke, U.F.H., Essen, P. van, Haaxma, C.A., Kluijtmans, L.A.J., Peters, G.T.M., Coene, K.L.M., Willemsen, M.A., Lefeber, D.J., Karnebeek, C.D. van, Hollander, Bibiche den, Rasing, Anne, Post, M.A., Klein, W.M., Oud, M.M., Brands, Marion M., Boer, L. de, Engelke, U.F.H., Essen, P. van, Haaxma, C.A., Kluijtmans, L.A.J., Peters, G.T.M., Coene, K.L.M., Willemsen, M.A., Lefeber, D.J., and Karnebeek, C.D. van
- Abstract
Contains fulltext : 235034.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
12. The role of clinical response to treatment in determining pathogenicity of genomic variants
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Shen, J.J., Wortmann, S.B., Boer, L. de, Kluijtmans, L.A.J., Huigen, M.C.D.G., Koch, J., Ross, S., Collins, C.D., Lee, R. van der, Karnebeek, C.D. van, Hegde, M.R., Shen, J.J., Wortmann, S.B., Boer, L. de, Kluijtmans, L.A.J., Huigen, M.C.D.G., Koch, J., Ross, S., Collins, C.D., Lee, R. van der, Karnebeek, C.D. van, and Hegde, M.R.
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Item does not contain fulltext, PURPOSE: The 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for the interpretation of sequence variants provide a framework to standardize terminology in the classification of variants uncovered through genetic testing. We aimed to assess the validity of utilizing clinical response to therapies specifically targeted to a suspected disease in clarifying variant pathogenicity. METHODS: Five families with disparate clinical presentations and different genetic diseases evaluated and treated in multiple diagnostic settings are summarized. RESULTS: Extended evaluations indicated possible genetic diagnoses and assigned candidate causal variants, but the cumulative clinical, biochemical, and molecular information in each instance was not completely consistent with the identified disease. Initiation of treatment specific to the suspected diagnoses in the affected individuals led to clinical improvement in all five families. CONCLUSION: We propose that the effect of therapies that are specific and targeted to treatable genetic diseases embodies an in vivo physiological response and could be considered as additional criteria within the 2015 ACMG/AMP guidelines in determining genomic variant pathogenicity.
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- 2021
13. Onderzoek naar mogelijk zorgwekkende stoffen in Nederlands oppervlaktewater
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Smit, E., Wassenaar, P., Boer, L. de, Janssen, N., Smit, E., Wassenaar, P., Boer, L. de, and Janssen, N.
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Waterbeheerders en drinkwaterbedrijven zetten zich in om mogelijk zorgwekkende stoffen zo vroeg mogelijk in beeld te krijgen. Het RIVM biedt daarvoor twee hulpmiddelen. Er is een lijst van potentieel Zeer Zorgwekkende Stoffen (pZZS) die onder de Europese stoffenwetgeving REACH zijn aangemerkt voor verder onderzoek. Daarnaast heeft het RIVM de ZZS similarity tool ontwikkeld om stoffen te screenen op zeer zorgwekkende gevaarseigenschappen. Door meetgegevens van effluent en oppervlaktewater te combineren met de pZZS-lijst en de ZZS similarity tool, is meer bekend over de aanwezigheid van mogelijk zorgwekkende stoffen in het Nederlandse watermilieu. Met zo’n vroege screening kunnen latere problemen worden voorkomen.
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- 2021
14. A Zebrafish Embryo Model for In Vivo Visualization and Intravital Analysis of Biomaterial-associated Staphylococcus aureus Infection
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Zhang, X., Boer, L. de, Stockhammer, O.W., Grijpma, D.W., Spaink, H.P., and Zaat, S.A.J.
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animal structures ,embryonic structures - Abstract
Biomaterial-associated infection (BAI) is a major cause of the failure of biomaterials/medical devices. Staphylococcus aureus is one of the major pathogens in BAI. Current experimental BAI mammalian animal models such as mouse models are costly and time-consuming, and therefore not suitable for high throughput analysis. Thus, novel animal models as complementary systems for investigating BAI in vivo are desired. In the present study, we aimed to develop a zebrafish embryo model for in vivo visualization and intravital analysis of bacterial infection in the presence of biomaterials based on fluorescence microscopy. In addition, the provoked macrophage response was studied. To this end, we used fluorescent protein-expressing S. aureus and transgenic zebrafish embryos expressing fluorescent proteins in their macrophages and developed a procedure to inject bacteria alone or together with microspheres into the muscle tissue of embryos. To monitor bacterial infection progression in live embryos over time, we devised a simple but reliable method of microscopic scoring of fluorescent bacteria. The results from microscopic scoring showed that all embryos with more than 20 colony-forming units (CFU) of bacteria yielded a positive fluorescent signal of bacteria. To study the potential effects of biomaterials on infection, we determined the CFU numbers of S. aureus with and without 10 µm polystyrene microspheres (PS10) as model biomaterials in the embryos. Moreover, we used the ObjectJ project file "Zebrafish-Immunotest" operating in ImageJ to quantify the fluorescence intensity of S. aureus infection with and without PS10 over time. Results from both methods showed higher numbers of S. aureus in infected embryos with microspheres than in embryos without microspheres, indicating an increased infection susceptibility in the presence of the biomaterial. Thus, the present study shows the potential of the zebrafish embryo model to study BAI with the methods developed here.
- Published
- 2019
15. Prediction of disease severity in multiple acyl-CoA dehydrogenase deficiency: A retrospective and laboratory cohort study
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Rijt, Willemijn J. van, Ferdinandusse, Sacha, Giannopoulos, Panagiotis, Ruiter, Jos P.N., Boer, L. de, Bosch, A.M., Wanders, Ronald J.A., Derks, Terry G.J., Rijt, Willemijn J. van, Ferdinandusse, Sacha, Giannopoulos, Panagiotis, Ruiter, Jos P.N., Boer, L. de, Bosch, A.M., Wanders, Ronald J.A., and Derks, Terry G.J.
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Contains fulltext : 208042.pdf (publisher's version ) (Open Access)
- Published
- 2019
16. Mutations in TBR1 gene leads to cortical malformations and intellectual disability
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Vegas, Nancy, Cavallin, Mara, Kleefstra, T., Boer, L. de, Philbert, Marion, Maillard, Camille, Besmond, Claude, Bahi-Buisson, N., Vegas, Nancy, Cavallin, Mara, Kleefstra, T., Boer, L. de, Philbert, Marion, Maillard, Camille, Besmond, Claude, and Bahi-Buisson, N.
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Item does not contain fulltext
- Published
- 2018
17. Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior
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Brouwer, A.P.M. de, Abou Jamra, Rami, Koertel, Nadine, Soyris, Clara, Polla, D.L., Safra, Modi, Pfundt, R.P., Boer, L. de, Koolen, D.A., Bokhoven, H. van, Schwartz, S., Brouwer, A.P.M. de, Abou Jamra, Rami, Koertel, Nadine, Soyris, Clara, Polla, D.L., Safra, Modi, Pfundt, R.P., Boer, L. de, Koolen, D.A., Bokhoven, H. van, and Schwartz, S.
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Item does not contain fulltext
- Published
- 2018
18. Quantification of gait in children with mitochondrial disease
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Koene, S., Stolwijk, N.M., Ramakers, R.E.F.S., Vries, M.C. de, Boer, L. de, Janssen, M.C.H., Groot, I.J.M. de, Smeitink, J.A.M., Koene, S., Stolwijk, N.M., Ramakers, R.E.F.S., Vries, M.C. de, Boer, L. de, Janssen, M.C.H., Groot, I.J.M. de, and Smeitink, J.A.M.
- Abstract
Contains fulltext : 194360.pdf (publisher's version ) (Open Access)
- Published
- 2018
19. The zebrafish embryo as a model to quantify early inflammatory cell responses to biomaterials
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Zhang, X., Stockhammer, O.W., Boer, L. de, Vischer, N.O.E., Spaink, H.P., Grijpma, D.W., and Zaat, S.A.J.
- Published
- 2017
20. Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity
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Mendes, M.I., Smith, D.E., Pop, A., Lennertz, P., Fernandez Ojeda, M.R., Kanhai, W.A., Dooren, S.J. van, Anikster, Y., Baric, I., Boelen, C., Campistol, J., Boer, L. de, Kariminejad, A., Kayserili, H., Roubertie, A., Verbruggen, K.T., Vianey-Saban, C., Williams, M., Salomons, G.S., Mendes, M.I., Smith, D.E., Pop, A., Lennertz, P., Fernandez Ojeda, M.R., Kanhai, W.A., Dooren, S.J. van, Anikster, Y., Baric, I., Boelen, C., Campistol, J., Boer, L. de, Kariminejad, A., Kayserili, H., Roubertie, A., Verbruggen, K.T., Vianey-Saban, C., Williams, M., and Salomons, G.S.
- Abstract
Contains fulltext : 182871.pdf (Publisher’s version ) (Open Access), We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase-the hydrolysis of N-acetyl-l-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC-MS/MS. Clinical data were obtained for 11 patients by means of questionnaires. Four patients presented with a non-typical clinical picture or with the milder form of CD, whereas seven presented with severe CD. The mutations found in the mild patients corresponded to the variants with the highest residual enzyme activities, suggesting that this assay can help evaluate unknown variants found in patients with atypical presentation. We have detected a correlation between clinical presentation, enzyme activity, and genotype for CD.
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- 2017
21. International Paediatric Mitochondrial Disease Scale
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Koene, S., Hendriks, J.C.M., Dirks, I., Boer, L. de, Vries, M.C. de, Janssen, M.C.H., Smuts, I., Fung, C.W., Wong, V.C., Coo, I.R. de, Vill, K., Stendel, C., Klopstock, T., Falk, M.J., McCormick, E.M., McFarland, R., Groot, I.J.M. de, Smeitink, J.A.M., Koene, S., Hendriks, J.C.M., Dirks, I., Boer, L. de, Vries, M.C. de, Janssen, M.C.H., Smuts, I., Fung, C.W., Wong, V.C., Coo, I.R. de, Vill, K., Stendel, C., Klopstock, T., Falk, M.J., McCormick, E.M., McFarland, R., Groot, I.J.M. de, and Smeitink, J.A.M.
- Abstract
Contains fulltext : 167896.pdf (publisher's version ) (Open Access), OBJECTIVE: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study. METHODS: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6-16 years) from five different expert centres from four different continents were evaluated in this study. RESULTS: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23-0.99). CONCLUSION: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials.
- Published
- 2016
22. High prevalence of complementary and alternative medicine use in patients with genetically proven mitochondrial disorders
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Franik, S., Huidekoper, H.H., Visser, G., Vries, M.B. de, Boer, L. de, Hermans-Peters, M., Rodenburg, R.J.T., Verhaak, C.M., Vlieger, A.M., Smeitink, J.A.M., Janssen, M.C.H., Wortmann, S.B., Franik, S., Huidekoper, H.H., Visser, G., Vries, M.B. de, Boer, L. de, Hermans-Peters, M., Rodenburg, R.J.T., Verhaak, C.M., Vlieger, A.M., Smeitink, J.A.M., Janssen, M.C.H., and Wortmann, S.B.
- Abstract
Contains fulltext : 152981.pdf (publisher's version ) (Closed access), Despite major advances in understanding the pathophysiology of mitochondrial diseases, clinical management of these conditions remains largely supportive, and no effective treatment is available. We therefore assumed that the burden of disease combined with the lack of adequate treatment leaves open a big market for complementary and alternative medicine use. The objective of this study was to evaluate the use and perceived effectiveness of complementary and alternative medicine in children and adults with genetically proven mitochondrial disease. The reported use was surprisingly high, with 88 % of children and 91 % of adults having used some kind of complementary and alternative medicine in the last 2 years. Also, the mean cost of these treatments was impressive, being
489/year for children and 359/year for adult patients. Over-the-counter remedies (e.g., food supplements, homeopathy) and self-help techniques (e.g., Reiki, yoga) were the most frequently used complementary and alternative therapies in our cohort: 54 % of children and 60 % of adults reported the various complementary and alternative medicine therapies to be effective. Given the fact that currently no effective treatment exists, further research toward the different therapies is needed, as our study clearly demonstrates that such therapies are highly sought after by affected patients. - Published
- 2015
23. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency
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Boer, L. de, Kluijtmans, L.A.J., and Morava, E.
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Genomic disorders and inherited multi-system disorders [IGMD 3] ,Glycostation disorders [IGMD 4] - Abstract
Item does not contain fulltext Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 mumol/l (normal: 20-55 muM) and total carnitine level had dropped to 12.7 mumol/l (normal: 25-65 muM). Transient carnitine deficiency was not likely anymore and DNA mutation analysis of the OCTN2 (SLC22A5) gene showed a homozygous c.136C>T (p.P46S) mutation, confirming the diagnosis of primary carnitine deficiency. We would like to emphasize that neonates with a primary carnitine deficiency might present with relatively high levels of total carnitine due to placental carnitine transfer, and also draw the attention to the importance of regular follow-up and the significance of genetic diagnostics in patients with a nonclassical presentation.
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- 2013
24. Integrated X-band FMCW front-end in SiGe BiCMOS
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Suijker, E.M., Boer, L. de, Visser, G.C., Dijk, R. van, Poschmann, M., Vliet, F.E. van, and TNO Defensie en Veiligheid
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Radar - Abstract
An integrated X-band FMCW front-end is reported. The front-end unites the core functionality of an FMCW transmitter and receiver in a 0.25 μm SiGe BiCMOS process. The chip integrates a PLL for the carrier generation, and single-side band and image-reject mixers for up- and down-conversion of the waveform. The front-end has been designed to co-operate with COTS integrated direct digital synthesisers and ADCs. The measurements show an output power of 0 dBm, P1dB at the receiver input of -11 dBm and a side band suppression of the mixer in the transmit chain of >40 dBc. The MMIC measures 1.8×1.5 mm2. This integrated front-end paves the path for future planar 2D integration of FMCW phased-array radars at X-band.
- Published
- 2010
25. Characteristics of Sotos syndrome
- Author
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Boer, L. de, Wit, J.M., Karperien, M., and Leiden University
- Subjects
Congenital defects - Published
- 2005
26. Decline of health status sub-domains by exacerbations of chronic obstructive pulmonary disease: a prospective survey
- Author
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Verhage, T.L., Boer, L. de, Molema, J., Heijdra, Y.F., Dekhuijzen, R., Vercoulen, J.H.M.M., Verhage, T.L., Boer, L. de, Molema, J., Heijdra, Y.F., Dekhuijzen, R., and Vercoulen, J.H.M.M.
- Abstract
Item does not contain fulltext, Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are held responsible for a decline in health status (HS). This may not apply equally to all exacerbations, because different definitions are required for quite different illnesses. Selection of definitions and the sensitivity of the HS instrument may affect results regarding the impact of exacerbations. Sensitivity of a new HS instrument, which covers different and more aspects, has not yet been tested, with respect to exacerbations. Objectives: Confirmation of the negative HS effect of exacerbations by using a highly differentiated instrument, and to evaluate which aspects of HS are affected most. Methods: One hundred and sixty-eight ambulatory patients with COPD were evaluated prospectively with regard to a wide range of HS aspects, at the beginning and end of a 1-year follow-up. Recording of symptom changes and treatment on monthly diary cards resulted in the identification of event-based exacerbations. HS was assessed via a newly validated instrument integrating both physiological and non-physiological sub-domains. Parametric correlations were calculated between exacerbation frequency and HS scores at the end of the study. Partial corre-lations were then explored using HS scores at baseline to correct for prior HS levels. Results: Correlations between -exacerbation frequency and HS sub-domains were found to be frequent, predominantly in non-physiological sub--domains. After correction for HS scores at baseline, only 2 sub-domains (belonging to the main domain 'Complaints') remained significantly but weakly correlated. Conclusion: Exacerbation frequency and HS show weak correlations after a year, but most of these disappear after correction for prior HS levels. In such exacerbations, aggravated HS probably takes much longer to manifest itself.
- Published
- 2013
27. Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency
- Author
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Zulfiqar, M., Lin, D.D., Graaf, M. van der, Barker, P.B., Fahrner, J.A., Marie, S. de, Morava, E., Boer, L. de, Willemsen, M.A.A.P., Vining, E., Horska, A., Engelke, U.F.H., Wevers, R.A., Maegawa, G.H., Zulfiqar, M., Lin, D.D., Graaf, M. van der, Barker, P.B., Fahrner, J.A., Marie, S. de, Morava, E., Boer, L. de, Willemsen, M.A.A.P., Vining, E., Horska, A., Engelke, U.F.H., Wevers, R.A., and Maegawa, G.H.
- Abstract
Item does not contain fulltext, Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease. J. Magn. Reson. Imaging 2013;37:974-980. (c) 2012 Wiley Periodicals, Inc.
- Published
- 2013
28. Validity of an automated telephonic system to assess COPD exacerbation rates.
- Author
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Bischoff, E.W.M.A., Boer, L. de, Molema, J., Akkermans, R.P., Weel, C. van, Vercoulen, J.H.M.M., Schermer, T.R.J., Bischoff, E.W.M.A., Boer, L. de, Molema, J., Akkermans, R.P., Weel, C. van, Vercoulen, J.H.M.M., and Schermer, T.R.J.
- Abstract
1 mei 2012, Item does not contain fulltext, Current tools for recording chronic obstructive pulmonary disease (COPD) exacerbations are limited and often lack validity testing. We assessed the validity of an automated telephonic exacerbation assessment system (TEXAS) and compared its outcomes with existing tools. Over 12 months, 86 COPD patients (22.1% females; mean age 66.5 yrs; mean post-bronchodilator forced expiratory volume in 1 s 53.4% predicted) were called once every 2 weeks by TEXAS to record changes in respiratory symptoms, unscheduled healthcare utilisation and use of respiratory medication. The responses to TEXAS were validated against exacerbation-related information collected by observations made by trained research assistants during home visits. No care assistance was provided in any way. Diagnostic test characteristics were estimated using commonly used definitions of exacerbation. Detection rates, compliance and patient preference were assessed, and compared with paper diary cards and medical record review. A total of 1,824 successful calls were recorded, of which 292 were verified by home visits (median four calls per patient, interquartile range three to five calls per patient). Independent of the exacerbation definition used, validity was high, with sensitivities and specificities between 66% and 98%. Detection rates and compliance differed extensively between the different tools, but were highest with TEXAS. Patient preference did not differ. TEXAS is a valid tool to assess COPD exacerbation rates in prospective clinical studies. Using different tools to record exacerbations strongly affects exacerbation occurrence rates.
- Published
- 2012
29. How do dyspnoea scales compare with measurement of functional capacity in patients with COPD and at risk of COPD?
- Author
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Boer, L. de, Asijee, G.M., Schayck, C.P. van, Schermer, T.R.J., Boer, L. de, Asijee, G.M., Schayck, C.P. van, and Schermer, T.R.J.
- Abstract
1 juni 2012, Item does not contain fulltext, BACKGROUND: In primary care, formal functional capacity testing is not always feasible. Guidelines for family practitioners suggest the use of dyspnoea scales to assess exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). AIMS: To examine whether the use of activity-based dyspnoea scales can substitute for actual functional capacity testing. METHODS: 128 subjects (49% at risk of COPD, 24% GOLD stage I, 17% GOLD stage II, 9% GOLD stage III) performed an Incremental Shuttle Walk Test (ISWT) and completed the Medical Research Council dyspnoea scale (MRC), Baseline Dyspnoea Index (BDI), Oxygen Cost Diagram (OCD), Clinical COPD Questionnaire (CCQ), and St George's Respiratory Questionnaire (SGRQ). RESULTS: Analysis of variance showed that the relationship between the ISWT and the MRC dyspnoea scale was statistically significant but moderate (p < 0.001, R2 = 0.166). Correlations between the ISWT and the other dyspnoea scales were also moderate (correlation coefficients 0.34-0.42). Combining the dyspnoea scales in one analysis resulted in a proportion of explained variance of the ISWT of 21.4% (R2 = 0.214). CONCLUSIONS: Dyspnoea scales cannot substitute for formal functional capacity testing. Authors of COPD guidelines should consider stating more specifically that the MRC and similar scales measure (self-reported) activity-related dyspnoea but cannot replace objectively measured functional capacity.
- Published
- 2012
30. Course of normal and abnormal fatigue in patients with chronic obstructive pulmonary disease, and its relationship with domains of health status
- Author
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Peters, J.B., Heijdra, Y.F., Daudey, L., Boer, L. de, Molema, J., Dekhuijzen, P.N.R., Schermer, T.R.J., Vercoulen, J.H.M.M., Peters, J.B., Heijdra, Y.F., Daudey, L., Boer, L. de, Molema, J., Dekhuijzen, P.N.R., Schermer, T.R.J., and Vercoulen, J.H.M.M.
- Abstract
Item does not contain fulltext, OBJECTIVE: To examine the difference between patients with normal and patients with abnormal fatigue on aspects of health status, and investigate the natural course of fatigue in patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS: Fatigue, physiological functioning, functional impairment, symptoms, and Quality of Life (QoL) were measured in 168 patients with COPD, and longitudinal data on fatigue of 77 patients were collected. RESULTS: Fifty percent of patients had abnormal fatigue. Patients with abnormal fatigue reported significantly more problems on the sub-domains of functional impairment (except actual physical activity), symptoms, and QoL as compared to patients with normal fatigue. With respect to physiological functioning patients with normal fatigue scores had better exercise capacity. Four years later the percentage of patients with abnormal fatigue was increased to 64%. In 1/3 of the patients an increase of more than the minimal clinically important difference was found. CONCLUSION: Many COPD patients suffer from abnormal fatigue. Patients with abnormal fatigue have more limitations on many aspects of health status, especially on symptoms, functional impairment, and QoL. PRACTICE IMPLICATIONS: Fatigue should be evaluated in usual care with a questionnaire that corrects for normal fatigue in order to tailor treatment to patients' need.
- Published
- 2011
31. Leiderschap van team- en afdelingsleiders
- Author
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Boer, L. de, Meijer, P.C. (Thesis Advisor), Butôt, I.J., Zeldenrijk, D.A., Boer, L. de, Meijer, P.C. (Thesis Advisor), Butôt, I.J., and Zeldenrijk, D.A.
- Published
- 2011
32. Depressive behaviour in children diagnosed with a mitochondrial disorder.
- Author
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Morava, E., Gardeitchik, T., Kozicz, L.T., Boer, L. de, Koene, S., Vries, M.C. de, McFarland, R., Roobol, T., Rodenburg, R.J.T., Verhaak, C.M., Morava, E., Gardeitchik, T., Kozicz, L.T., Boer, L. de, Koene, S., Vries, M.C. de, McFarland, R., Roobol, T., Rodenburg, R.J.T., and Verhaak, C.M.
- Abstract
1 augustus 2010, Contains fulltext : 88321.pdf (publisher's version ) (Closed access), A higher incidence of depression has been described in adults with primary oxidative phosphorylation disease. We evaluated the psychological characteristics of eighteen non-retarded pediatric patients diagnosed with a disorder of the oxidative phosphorylation. We found significantly higher rate of withdrawn, depressive behaviour compared to population norm scores, to children with other types of inborn errors of metabolism and also in comparison to patients with Sotos syndrome. The occurrence of depressive behaviour showed no correlation with the degree of mitochondrial dysfunction. These findings support the hypothesis that mood disorders could be associated to abnormal cerebral energy metabolism.
- Published
- 2010
33. Heupdysplasie bij honden
- Author
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Boer, L. de, Hazewinkel, H.A.W. (Thesis Advisor), Lavrijsen, I.C.M., Boer, L. de, Hazewinkel, H.A.W. (Thesis Advisor), and Lavrijsen, I.C.M.
- Abstract
Canine Hip dysplasia (CHD) is a progressive disorder of the canine hip which consists of a genetic and environmental component. For this study the evaluations of the radiographic images of 23096 dogs originating from 38 different breeds, and officially evaluated since 2002, were collected. Based on these evaluations the prevalence of CHD in these breeds in The Netherlands has been determined and compared with [revalences as reported in international literature. The difference in prevalence of CHD in the period 1996-2002 and 2003-2009 has been determined for each breed. This difference appeared to be significantly reduced for 7 of the evaluated breeds, determined by using a Chi2-test. When comparing the breeding policy of these breeds to the breeding policy of breeds that didn’t show any improvement, it showed that in only two breeds positive HD (grade C) was accepted for breeding. In the other 5 breeds, breeding with HD positive dogs was not permitted. In the five most evaluated breeds the influence of gender on prevalence of CHD showed significance in 3 breeds. This may be a result of the uneven distribution of the gender or the difference in age at the time of evaluation between the genders. Less than 7% of all born animals are used in breeding. This creates a bottleneck which has to be kept in mind when creating breeding policies. Ways to lower the prevalence of CHD besides excluding animals with CHD from breeding, could be screening of the majority of the population, progeny research and import of disease-free breeding material.
- Published
- 2010
34. Genotype-phenotype correlation in patients suspected of having sotos syndrome.
- Author
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Boer, L. de, Kant, S., Karperien, M., Beers, L. van, Tjon, J., Vink, G.R., Tol, D. van, Dauwerse, H.G., Cessie, S. le, Beemer, F.A., Burgt, C.J.A.M. van der, Hamel, B.C.J., Hennekam, R.C.M., Kuhnle, U., Mathijssen, I.B., Veenstra-Knol, H.E., Stumpel, C.T., Breuning, M.H., Wit, J.M., Boer, L. de, Kant, S., Karperien, M., Beers, L. van, Tjon, J., Vink, G.R., Tol, D. van, Dauwerse, H.G., Cessie, S. le, Beemer, F.A., Burgt, C.J.A.M. van der, Hamel, B.C.J., Hennekam, R.C.M., Kuhnle, U., Mathijssen, I.B., Veenstra-Knol, H.E., Stumpel, C.T., Breuning, M.H., and Wit, J.M.
- Abstract
Contains fulltext : 58369.pdf (publisher's version ) (Open Access), BACKGROUND: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. METHODS: Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained. RESULTS: In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups. CONCLUSIONS: In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not.
- Published
- 2004
35. A review of methods supporting supplier selection
- Author
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Boer, L. de, Labro, E., and Morlacchi, P.
- Published
- 2001
- Full Text
- View/download PDF
36. Outranking methods in support of supplier selection
- Author
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Boer, L. De, Wegen, L. Van der, and Telgen, J.
- Published
- 1998
- Full Text
- View/download PDF
37. Post-menopausal and chronological age have divergent effects on pituitary and hypothalamic function in episodic gonadotrophin secretion
- Author
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Lambalk, C. B., Boer, L. de, Schoute, E., Popp-Snyders, C., and Schoemaker, J.
- Abstract
OBJECTIVE Ageing is known to reduce gonadotrophin secretion in post-menopausal women. To what extent the hypothalamus and pituitary are involved in this process is not clear. The aim of this study was to compare pulse characteristics of FSH and LH in relation to chronological and post-menopausal age. Based on the gonadotrophin response to GnRH, we assessed the extent to which pituitary and/or hypothalamic ageing is responsible for the observed changes. DESIGN Blood samples were obtained from post-menopausal women every 10 minutes for 6 hours. Subsequently, 100 μg GnRH was administered intravenously and blood samples taken after 30, 60 and 90 minutes. PATIENTS Twenty healthy women aged 4772 years and between 1 and 30 years after the menopause. MEASUREMENTS Plasma LH and FSH were measured by immunoradiometric assay. Pulses were identified by a computerized pulse detection program. End points were the mean number and amplitude of pulses, the mean LH and FSH concentrations during the 6-hour study period and the maximal LH and FSH increments following GnRH. RESULTS Mean LH and FSH levels did not change with chronological age but the LH pulse frequency declined significantly and the response to GnRH increased. Mean LH levels declined with post- menopausal age without alteration in LH pulse frequency but with a significant decrease in pituitary LH response to GnRH. FSH levels remained unchanged. CONCLUSIONS Post-menopausal ageing seems to have a major suppressive effect on pituitary gonadotroph function, while chronological ageing mainly affects the hypothalamic regulation of LH secretion.
- Published
- 1997
- Full Text
- View/download PDF
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