Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie最新文献

Cancer malignancy is characterized by cancer cell invasion within local and distant ecosystems. Data from our laboratory are reviewed with a focus on cross-signaling between cancer cells and host cells such as myofibroblasts, mesenchymal stem cells and adipocytes. Invasion-associated cellular activities, namely epithelial to mesenchymal transition, homotypic and heterotypic cell-cell adhesion, cell-matrix adhesion, migration, proteolysis and vesicle exocytosis, depend on branching networks of signal transduction pathways including activation of trimeric G proteins, phosphoinositide 3-kinase, src, signal transducer and activator of transcription and the Rab, Rac and Rho family of small GTPases. The role of proteolysis in invasion is not limited to breakdown of extracellular matrix but also causes cleavage of pro-angiogenic fragments from cell surface glycoproteins. Some cell types or molecules implicated in invasion-associated activities may serve as prognostic biomarker or as target for patient-tailored therapy.

The Family Influences on Food Intake study (FIFI), is a longitudinal study on dietary habits of young children and the primary socialization of these habits during childhood and during the transition into adolescence. Special attention is paid to the development, validation and feasibility of instruments measuring as well dependent as independent variables useful for large scale surveys. Parents of preschool children from the first year (+/-3 years of age) of 56 school departments were asked to complete a self-administered questionnaire biennially. Data of 862 children was available for the first measurement (2008). A web based dietary record tool was developed to investigate the relative validity of the Food Frequency Questionnaire (FFQ) used in the study. Two hundred and seventeen parents completed the online tool for three non-consecutive days. The feasibility of the online data collection is investigated and the reported intake is compared with the FFQ estimates. Associations between nutritional knowledge and attitudes of the children's mothers and dietary patterns of the children (FFQ) are investigated as well as relations between parent and child characteristics and fruit and vegetable intake. Additionally, 70 teachers completed a questionnaire on their attitudes towards the school food policy. The teachers' responses are compared with responses of parents from a previous study. Finally, the feasibility of an animated web based fruit and vegetables preferences tool, to be used in the follow up surveys, has been investigated in 4-6 years old (n=139 for fruit and n=135 for vegetables). The findings are summarized in the present paper.

This PhD thesis indicated by a literature review and a prospective study that maternal obesity is associated with serious complications for both mother and child. This is a problem since already 9% of the pregnant women at the antenatal department of the University Hospital Leuven was obese during 2006. A prospective study with 142 women showed that maternal obesity is also associated with a lower diet quality during pregnancy compared to normal weight pregnant women. To reduce the high prevalence of excessive gestational weight gain among obese pregnant women and to improve their low diet quality, a randomized controlled trial with 2 intervention groups with a different intensity of nutritional guidance was set up. Both interventions improved dietary habits, but affecting physical activity level and gestational weight gain remains a challenge. During this thesis 2 practical tools for all pregnant women and their health care providers were developed: weight gain percentile charts for each body mass index category and a website giving information on nutrition, physical activity, and weight gain during pregnancy. Besides obese pregnant women, pregnant women with a history of bariatric surgery are also a high-risk population. Even though the obesity related pregnancy complications decrease after the surgery induced weight loss, other complications such as internal hernias and nutritional deficiencies with potential lethal consequences have been identified. A multidisciplinary follow-up during pregnancy with routine screening for nutritional deficiencies with attention for the fat-soluble vitamins and patient tailored nutritional supplementation seems required.

This contribution contains a synthesis of the results of two socio-cultural anthropological research projects among Orthodox Jewry concerning the 'identity', 'emancipation' and 'integration' of women. First the meaning of female religiosity from the perspective of strictly Orthodox, including Chassidic, women is discussed. Whereas in the public and institutional religious sphere men are the paradigmatic "Orthodox Jews", due to the sacralisatie of daily life, religious roles for women are not less extensive or any less important but are predominantly situated in the private and domestic sphere. It is argued that from an anthropological and gender critical perspective, women's religious gender identity therefore cannot be straightforwardly interpreted as either "oppressed" nor "emancipator". The second study concerns Jewish Orthodox women (ranging from strictly to modern Orthodox) in Antwerp who transgress religious gender norms by studying or working in the surrounding secular society. Their life stories show very different trajectories of encounters with the "outside world" that are sometimes enriching yet sometimes also experienced in terms of intercultural conflicts. It is concluded that maintaining cultural identity, next to emancipation and integration from within the Orthodox Jewish community is not impossible, but that this requires minimal mutual dialogue and understanding.

Megakaryopoiesis and platelet production are very complex processes, orchestrated by different growth factors, cytokines and transcription factors. It's only recently that a role was assigned for the pituitary adenylyl cyclase-activating peptide (PACAP) and the vasoactive intestinal peptide (VIP) via their common Gs-coupled receptor VPAC1 in this process. The basis for this idea originated from studies in two related patients with a partial trisomy 18p11 and therefore carrying 3 copies of the PACAP gene and elevated PACAP concentrations in their plasma which resulted in a bleeding tendency with thrombopathy and a mild thrombocytopenia. This platelet functional and formation defect could be phenocopied in transgenic megakaryocyte specific PACAP-overexpressing mice. The addition of PACAP or VIP to hematopoietic stem cells resulted in an decreased megakaryocyte maturation and DNA polyploidization. In contrast, mice subcutaneously injected with inhibitory anti-PACAP (PP1A4) or anti-VPAC1 (23A11) antibodies presented with increased platelet numbers. This last concept was the basis for the development of these antibodies for the treatment of different types of thrombocytopenia as the therapeutic value for these antibodies was established in mice with a low platelet count due to chemotherapy, anti-platelet antibodies, a congenital factor of after bone marrow transplantation. For all models, the addition of 23A11 or PP1A4 resulted in an increased platelet recovery compared to the control antibody. Further studies are needed to identify the downstream signal transduction components after VPAC1 stimulation in megakaryocytes and platelets.

Critically ill patients face a high risk of death, which is mostly due to non-resolving multiple organ failure. The plethora of endocrine and metabolic disturbances that hallmark critical illness may play a key role. The major part of our research performed during the period 2004-2009 focused on the disturbed glucose metabolism that commonly develops during critical illness. The onset of this research interest was the landmark randomized clinical study on strict blood glucose control (80-110 mg/ dl) with intensive insulin therapy performed by Prof. Van den Berghe and our clinical team members. This study, published in 2001 in the New England Journal of Medicine, showed reduced morbidity and improved survival with intensive insulin therapy versus toleration of hyperglycemia up to 215 mg/dl. This review summarizes our findings in both patients and animal models on mechanisms contributing to the clinical benefits of strict blood glucose control. Intensive insulin therapy appeared to lower blood glucose levels by ameliorating insulin sensitivity and stimulation of glucose uptake in skeletal muscle, whereas hepatic insulin resistance was not affected. The therapy also improved the lipid profile and the immune response and attenuated inflammation. Maintenance of strict normoglycemia appeared essentially most important, rather than elevating insulin levels. Avoiding hyperglycemia protected the endothelium and the mitochondria. In our animal model, nutritional interventions counteracted the hypercatabolic state of critical illness and insulin improved myocardial contractility, but only when normoglycemia was maintained. Interestingly, we identified the adipose tissue as a functional storage depot for toxic metabolites during critical illness.

Glaucoma is an important cause of blindness. Therefore, the optimalisation of glaucoma surgery might have an important impact on the visual prognosis and the quality of life of glaucoma patients. This project focuses on the development of antifibrotic strategies that would inhibit the scarring of the created fistula, and thus improve the outcome after glaucoma surgery. We found that the vascular growth factor VEGF that is mostly known for its role in blood vessel formation also plays a role in postoperative wound healing. Furthermore, we studied the potential of anti-VEGF therapy to inhibit excessive wound healing (scar formation) after glaucoma surgery. Indeed, both in vitro and in vivo, VEGF prove to be efficacious to reduce scar formation, and thus improve the prognosis after glaucoma surgery. This fundamental research translated into a prospective clinical study, in which anti-VEGF is administered during glaucoma surgery, to improve the outcome after the surgery. We therefore hope that this translational research will indeed result in a better prognosis and quality of life for our glaucoma patients.

Although no randomized trials are available, surgical resection is a widely accepted treatment for selected patients with pulmonary metastases. Specific criteria have been well defined and a macroscopic complete resection should be obtained. Important prognostic factors include histology, number of metastases and disease-free interval. However, even after complete resection, 5-year survival rates remain disappointingly low and many patients will have recurrent disease confined to the chest. For this reason, locoregional therapies are extensively investigated at the present time. These include biochemical and biophysical methods. Due to toxicity of high doses of intravenous chemotherapy, the main purpose is to deliver high-dose chemotherapy to the lung without systemic side-effects. Chemo-embolization, pulmonary artery infusion and isolated lung perfusion are most intensively studied. These techniques were found to be feasible and are able to deliver a high local concentration of chemotherapeutic drugs. The results of further phase II trials are awaited for to determine their effect on local recurrence and long-term survival.