Repository hosted by TU Delft Library

Objective: Many obstetric interventions are performed to improve long-term neonatal outcome. However, long-term neonatal outcome is usually not a primary outcome because it is time-consuming and expensive. The aim of this project was to identify different perinatal risk indicators and to develop prediction models for neurologic morbidity at 2 and 5 years of age. Study design: Data from a Dutch cohort study of preterm and small-for-gestational-age infants was used. Neonates who were born in The Netherlands in 1983 with a gestational age of <34 weeks and without congenital abnormalities were included (n = 753). Infants were divided in 3 groups: no handicap, minor handicap, and major handicap. Results: Common risk indicators for major handicaps at 2 and 5 years of age were male sex (odds ratio, 2.7 and 3.0, respectively), seizures after <2 days of life (odds ratio, 5.8 and 5.8, respectively), and intracranial hemorrhage (odds ratio, 3.8 and 2.6, respectively). Conclusion: In this cohort, male sex, intracranial hemorrhage, and seizures seem to be important risk indicators for long-term neurologic morbidity. © 2011 Mosby, Inc. All rights reserved.

Transient neonatal hypothyroxinemia is very common in preterm infants. The literature on the effect of this hypothyroxinemia is, however, controversial, and large or long-term follow-up studies are not available. In a nationwide prospective follow-up study on very preterm and (or) very low birth weight infants (n = 717), we studied the relationship between thyroxine levels in the 1st wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age. Thyroxine concentrations from filter paper eluates were determined in 717 infants: 32% had levels of more than 3 SD below the mean (<60 nmol/L). The percentage of infants with such low levels increased with decreasing gestational age. At the age of 5 y, 96% of survivors (n = 640) were available for extensive neurodevelopmental examination: 85 (13.3%) had a disability and 92 (14.3%) a handicap. At the age of 9 y, 83% of survivors (n = 552) answered a questionnaire on school performance: 300 (54.3%) were in mainstream education in a grade appropriate for age, 151 (27%) were in mainstream education with grade retention, and 101 (18.3%) were in special education. Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors (odds ratio, 1.3) Whether this relationship is causal should be investigated. If a causal relationship exists, substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities, both common sequelae of very preterm birth.

Background: In many agricultural districts in Sri Lanka, pesticide poisoning is a leading cause of death. This study aims to evaluate the impact of pesticide use on Sri Lankan farmers' health. Methods: A total of 260 subjects were surveyed in both a low and a high exposure period. Acetylcholinesterase activity was measured and data on symptoms were collected with questionnaires. Results: Twenty-four percent of surveyed farmers had suffered at least once from acute pesticide poisoning. Farmers showed significantly more inhibition of cholinesterase activity than controls. Acute symptoms indicative for exposure to cholinesterase-inhibiting pesticides were associated with farming and a higher degree of cholinesterase suppression (more than 13% inhibition). Integrated Pest Management (IPM) training seemed to result in less insecticide use, and less cholinesterase inhibition. Conclusions: Our results suggest that occupational acetylcholinesterase-inhibiting insecticide exposures have a negative impact on Sri Lankan farmers' health. Overall reduction in pesticide use seems the best option to protect farmers from the adverse effects of pesticides. © 2003 Wiley-Liss, Inc.

Aim: To determine whether paediatricians that examine, in regular clinical practice, very preterm and very-low-birthweight children at 5 y of age detect neurological impairments and functional motor problems in these children. Methods: We compared a paediatric judgement, a standardized neurological examination (Touwen examination) and a screening of motor development (Denver Developmental Screening Test; DDST) with the Movement ABC in 396 5-y-old very preterm and low-birthweight children. Results: The Movement ABC detected clinically important motor disorders in 20.5% and borderline disturbances in 22.5% of the children. Compared to the Movement ABC, the sensitivity of the paediatric judgement was 0.19, Touwen examination 0.62 and DDST 0.52; the negative predictive values were 0.61, 0.74 and 0.69, respectively. Conclusion: Paediatric assessment of motor development in 5-y-old very preterm and low-birthweight children generally is not sensitive enough to detect functional motor problems. The Movement ABC should be added to the assessment of the motor development of very preterm and low-birthweight children at 5 y of age. © 2006 Taylor & Francis.

In the development of multiple sclerosis (MS), (re)activation of infiltrating T cells by myelin-derived Ags is considered to be a crucial step. Previously, αB-crystallin has been shown to be an important myelin Ag to human T cells. Since αB-crystallin is an intracellular heat shock protein, the question arises at what stage, if any, during lesional development in MS this Ag becomes available for CD4+ T cells. In 3 of 10 active MS lesions, αB-crystallin could be detected inside phagocytic vesicles of perivascular macrophages, colocalizing with myelin basic protein and myelin oligodendrocyte glycoprotein (MOG). Although the detectability of MOG in phagosomes is considered as a marker for very recent demyelination, MOG was detected in more macrophages and in more lesions than αB-crystallin. The disappearance of αB-crystallin from macrophages even before MOG was confirmed by in vitro studies; within 6 h after myelin-uptake αB-crystallin disappears from the phagosomes, αB-Crystallin-containing macrophages colocalized with infiltrating T cells and they were characterized by expression of MHC class II, CD40, and CD80. To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with whole myelin membranes. These macrophages activated both myelin- primed and αB-crystallin-primed T cells in terms of proliferation and IFN-γ secretion. In addition, αB-crystallin-pulsed macrophages activated myelin- primed T cells to the same extent as myelin-pulsed macrophages, whereas myelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, αB-crystallin is available for functional presentation to T cells early during inflammatory demyelination. Chemicals/CAS: Antigens, CD40; Antigens, CD80; Autoantigens; Cathepsins, EC 3.4.-; Crystallins; Histocompatibility Antigens Class II; Myelin Proteins

Early recognition of whether a product has potential as a new therapy for treating multiple sclerosis (MS) relies upon the quality of the animal models used in the preclinical trials. The promising effects of new treatments in rodent models of experimental autoimmune encephalomyelitis (EAE) have rarely been reproduced in patients suffering from MS. EAE in outbred marmoset monkeys, Callithrix jacchus, is a valid new model, and might provide an experimental link between EAE in rodent models and human MS. Using magnetic resonance imaging techniques similar to those used in patients suffering from MS pathological abnormalities in the brain, white matter of the animal can be visualized and quantified. Moreover, NMR spectroscopy, in combination with pattern recognition, offers an advanced uroscopic technique for the identification of biomarkers of inflammatory demyelination.

Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo models for MS. In an in vitro setting mAb against CD81 significantly reduced monocyte transmigration across brain endothelial cell monolayers, both in rodent and human models. Interestingly, leukocyte as well as endothelial CD81 was involved in this inhibitory effect. To assess their therapeutic potential, CD81 mAb were administered to mice suffering from experimental autoimmune encephalomyelitis (EAE). We found that Eat2, but not 2F7 mAb directed against mouse CD81 significantly reduced the development of neurological symptoms of EAE when using a preventive approach. Concomitantly, Eat2 treated animals showed reduced inflammation in the spinal cord. We conclude that CD81 represents a potential therapeutic target to interfere with leukocyte infiltration and ameliorate inflammatory neurological damage in MS. © 2008 Elsevier Inc. All rights reserved.