Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie最新文献

Based on an estimated incidence of cancer during pregnancy of 1 per 1000-1500 pregnancies, annualy 3000-5000 new patients can be expected in Europe. The treatment of cancer in pregnant women is a challenge since both the maternal and the foetal well-being need to be considered. This study was initiated to gain better insights into the problems associated with cancer and chemotherapy during pregnancy. A multicentric registration study was set up to evaluate the currently applied treatment modalities for cancer during pregnancy, and the consequences of their use for the pregnancy. Secondly, a preclinical and clinical pharmacological study addressing pharmacokinetics of chemotherapy in pregnant women and transplacental passage of chemotherapy was performed. Thirdly, we investigated the effects of prenatal exposure to chemotherapy on foetal neurological development. We observed an equal distribution of tumour types between pregnant and age matched nonpregnant women. Data on neonatal outcome suggest that exposure to chemotherapy in the 2nd or 3rd trimester of pregnancy does not worsen the outcome. This finding is explained by the fact that chemotherapy is not administered during the period of organogenesis and by the foetal protection by the placental barrier-function. Physiological changes of pregnancy resulted in a decreased plasma drug exposure of chemotherapeutic agents. Before major conclusions can be drawn with regard to the long term foetal outcome and the efficacy of chemotherapy during pregnancy, more patients and a longer follow up period is required. Therefore, this research project is continued and expanded nationally and internationally.

Translational research and biobanking are "in", also in Flanders and in Belgium. In Flanders the Advice report 120 from the Flemish Council for Science and innovation, entitled "Extension of translational research in Flanders" paved the way for the Center for Medical Innovation. The Center for Medical Innovation aims at promoting collaboration between Flemish Universities, university hospitals, pharma and biotech industry and the Flemish Government specifically in the domain of translational research. The Initiative # 27 of the Cancer plan from the Federal Government aims at financing a virtual interuniversity tumor bank in order to promote "cancer" translational research in a collaborative network between academic structures, general hospitals en different industrial partners (pharmacy, biotechnology, diagnostics, ...) active in research in Belgium. However, the scientific interest in the human tissues is not new, at all. This text aims at giving an overview of the development and evolutions of "biobanking" initiatives.

The main purpose for human assisted reproductive technologies (ART) is clearly to bypass reproductive failures. This purpose is totally different from the aims in animal ART, being genetic improvement and more recently conservation of endangered species. Apoptosis or programmed cell death has been detected before implantation in in vivo as well as in vitro embryos and might contribute to lower developmental competence and embryonic losses of in vitro embryos. In vitro embryo quality is clearly jeopardized by quality of the gametes (oocytes and spermatozoa) and suboptimal culture condition, but there is no consensus on which factor is most important in the incidence of apoptosis during early embryo development. The objective of the present study was to unravel the contribution of both male and female gamete quality to the incidence of apoptosis of bovine embryos produced in vitro. In vivo bull fertility expressed a very low correlation with cleavage rate and blastocyst yield. In contrast, developmental kinetics and oocyte diameter are important markers of embryo developmental potential and embryo quality in terms of the appearance of apoptosis, indicating a significant maternal effect on embryo quality.

During the last decades a new in vitro technique has entered the field of allergy diagnosis, that is, component-resolved allergy diagnosis (CRD). In contrast to traditional specific IgE (sIgE) assays, CRD does not rely upon whole extract preparations from native allergens but on quantification of sIgE antibodies to single protein components, purified from natural sources or obtained by recombinant techniques. At present, it emerges that CRD can improve management of the allergic patient as it allows (to some extent) to discriminate between clinically significant and irrelevant sIgE result and to establish sensitization patterns with particular prognostic outcomes. Nevertheless, further clinical validation is mandatory before the technique can enter mainstream application. By no means can CRD currently be considered as a substitute to traditional sIgE assays.

In the years following WW II, all 'Western' countries were struck by recurrent epidemics of infantile paralysis (poliomyelitis). In the early 1950s, a vaccine developed by Jonas Salk in Pittsburgh, became available in the U.S. and Canada. In 1953-54 central virology laboratories in Sweden, Denmark and France were already well advanced in setting up local production lines of the vaccine. At that point in time, the Catholic University of Leuven, on the initiative of the young microbiology professor, Piet De Somer, and in collaboration with the pharmaceutical concern R.I.T. (Recherches et Industries Thérapeutiques, Genval, Belgium), erected a new, multidisciplinary medical research institute, the Rega Institute. One of the research units to be headed by De Somer was destined to introduce the relatively new discipline of virology. As a test case, De Somer decided to venture on developing a production line of the Salk vaccine. In less than one year's time, the project was successful, such that Belgium became one of the first European countries to be self-supporting for its vaccine supply and to be able to initiate a large-scale vaccination campaign. The planning, preparation and execution of the project was accompanied by an extensive correspondence of De Somer with experts and other concerned parties in Belgium and abroad. This correspondence has been preserved and allows for a detailed reconstruction of the remarkable achievement.

Lung transplantation is a life-saving treatment option in carefully selected patients with end-stage lung disease. Life expectancy after this form of treatment has progressively increased with a current survival of 90% after 1 year, 70% after 5 years, and 50% after 10 years in experienced centers. Apart from a survival benefit, this treatment aims to improve the quality of life. Bilateral lung transplantation is the type of operation that is performed most frequently because of superior survival results, especially when chronic rejection develops. Single lung transplantation is now reserved for older patients with pulmonary fibrosis. Heart-lung transplantation is rarely done, only in patients with Eisenmenger's syndrome or complex congenital heart disease. Belgium is one of the world leaders in terms of number of deceased organ donors with a lung recovery rate of about 35%. With a total of 8.3 lung transplants per million population, Belgium is currently the number 1 in the world. The procedure nowadays is performed in 4 University Hospitals (UA-KUL-ULB-UCL) in the country. Between 1983 and 2009, nearly 1000 proedures were performed. The most common indication was emphysema, followed by cystic fibrosis, pulmonary fibrosis, pulmonary arterial hypertension, and Eisenmenger's syndrome. Further application of this treatment option is hampered by several problems such as donor organ shortage, primary graft dysfunction, chronic rejection presenting as bronchiolitis obliterans syndrome, and side effect of chronic immunosuppression. In the Laboratory for Experimental Thoracic Surgery and the Laboratory for Pneumology at the Katholieke Universiteit Leuven, intensive research is done by our group looking for new methods to increase the lung donor pool and to prevent and to treat chronic rejection.

The use of devices for cosmetic treatment and esthetic skin treatments has increased in recent years. Some of these treatments, especially those that pass the dermo-epidermal barrier, can cause complications and secondary effects. In Belgium, there is almost no legislation concerning this type of treatment. Therefore, the Belgian Health Council has advised in a recent publication of January 2011, that there is an urgent need for adequate regulation concerning the use of devices for cosmetic treatment and esthetic skin treatment. The Council suggests to start up an evaluation commission, and also to have strict guidelines about the training needed for professionals who do this kind of treatments. Inspections by a competent authority should control the adherence to the forthcoming legislation.

Structural biologists focus on the structure of biomolecules. Several techniques are available to study the structure adopted by a biomolecule and unravel how this structure is related to its constitution and function. For their biological role in a functioning cell or organism, biomolecules interact with each other and/or rather small molecules in their environment. Drugs can exploit interaction with biomolecules to manipulate their biological function to obtain a therapeutic effect. Structure determination of biomolecules that (could) serve as therapeutic target is an important starting point in rational drug design. Once the structure of a biological target is known, a potential binding site for drugs and possible interactions at this site have to be identified. In the stage of drug design this information is a valuable input for modeling experiments. They can virtually scan libraries of compounds by docking them into the binding site. This strategy ranks potential ligands that can be chemically modified to optimize their interaction at the binding site ('lead optimization') in order to improve affinity and selectivity for the biomolecular target. Modeling can also be used to virtually 'build' new molecules starting from possible interactions and shape of the target binding site ('de novo design'). Structural biology can contribute in different stages of drug development to direct the process or optimize existing compounds.