Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie最新文献

In infertile women, the prevalence of thyroid autoimmunity (TAI) is significantly higher compared to that in parous age-matched women. This is especially the case in women with endometriosis and the polycystic ovarian syndrome. TAI does not interfere with normal fetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without TAI. During the first trimester however, pregnant women with TAI carry a significantly increased risk for a miscarriage compared to women without TAI, even when euthyroidism was present before pregnancy. It has further been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with TAI. It is therefore advised to measure thyroid function and detect TAI in infertile women, before ART, and to follow-up these parameters after COH and during pregnancy when TAI was initially present. Women with thyroid dysfunction before or at early gestation stages should be treated with 1-thyroxine to avoid assisted pregnancy or further pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with TAI remains controversial and needs further investigation.

Obesity has reached epidemiological proportions in Europe and the burden of diseases attributable to nutrition is substantial. Under the impetus of the World Health Organisation (WHO), member states have been urged to develop national action plans for nutrition and physical activity. This study describes what has been done in terms of nutrition policy at national level in the member states of the European Union right before its enlargement in 2004. It is a critical review of publicly available policy documents on nutrition and physical activity. The background idea was to assist the initiative of the Belgian food industry to play a proactive role in the development of a Belgian nutrition action plan. At the time of writing, in total six out of the fifteen EU member states namely Sweden, Finland, Denmark, France, the Netherlands and the United Kingdom, reported to have an operational national nutrition plan. By the end of the year 2004, another four countries are expected to have their plan finalised. In line with WHO guidelines, all nutrition plans in this study acknowledge the importance of a multidisciplinary approach and promote stakeholder involvement at some point. Most of the plans however, do not elaborate on their specific role and strategies that will be used to do so. It seems that stakeholder mobilisation is largely restricted to the implementation phases. All operational nutrition plans envisage reducing social disparities. Long-established vulnerable groups in society such as pregnant women, children and elderly are targeted. Considerable variability was observed for nutritional objectives and dietary recommendations between the different countries. Nutrition surveillance and monitoring activities seem to vary considerably between the different action plans. None of the countries except Denmark documents the theoretical foundations and development process of their nutritional surveillance system. National nutrition policy in Europe is clearly in a state of flux and the centre of gravity seems to move away from Scandinavia. Although the importance of nutritional surveillance, comprehensive approach to nutritional problems and stakeholder involvement is recognised by the action plans, the rationale, justification and mechanisms for it is vaguely described. Our findings call for increased efforts to strengthen the evidence base of public health nutrition policy. To achieve this however, systematic evaluations and proper reporting of which health and nutrition promotion strategies work in the different countries in the EU are urgently needed.

There are, at present, only three (classes of) compounds that could be considered for the chemotherapy and -prophylaxis of influenza virus infections: ribavirin, amantadine/rimantadine and the neuraminidase inhibitors zanamivir and oseltamivir. The latter, also known under the registered name of Tamiflu, seems to be the most indicated, as it is effective against influenza A and B virus infections and can be conveniently administered orally in capsule form (twice daily). In the wake of a potential influenza A virus pandemic it may be advisable to have at hand sufficient amounts of oseltamivir to affront such emerging infection.

Until recently, it was thought that pigs were required as intermediate hosts for the transmission of avian influenza viruses to humans and this hypothesis is based on three suppositions: (1) Pigs are more susceptible to avian influenza viruses than humans. (2) Pigs are the single animal species with receptors preferred by both avian (alpha 2-3 linked sialic acid to galactose) and human (alpha 2-6 linked sialic acid) influenza viruses, which supports their role as "mixing vessels" for reassortment between human and avian viruses. In addition, influenza viruses from aquatic birds can adapt to "human" receptors in the pig. (3) Genetic reassortment between avian and human influenza viruses, which is an important mechanism for the emergence of new pandemic human strains, frequently occurs in pigs in nature. The first part of this paper presents some critical (counter) arguments for these suppositions. The second part focuses on the role of swine in recent cases of highly pathogenic avian influenza (HPAI) in humans in The Netherlands and in Southeast Asia. The respective HPAI viruses have spread directly from infected poultry to both humans and pigs, and pigs did not serve as an intermediate host between birds and humans. Fortunately, it is unlikely that these viruses would spread widely in the human population, unless mutations or genetic reassortment would occur. In theory such genetic changes might occur in the pig. However, it is currently impossible to analyse the risk of the pig in the introduction of new avian influenza strains in the human population, because the basic questions about the replication and pathogenesis of such viruses in swine are still unanswered.

Avian influenza (AI) is a highly contagious disease for birds, which can easily take epidemic proportions when appropriate and efficacious measures are not taken immediately. Influenza viruses can vary in pathogenicity from low to medium or highly pathogenic. A low pathogenic strain can become highly pathogenic by introduction of new mutations (insertions, deletions or substitutions) in the cleavage site of the haemagglutinin during circulation in chickens. Up till now only H5 and H7 strains gave rise to highly pathogenic strains in this manner. At present the avian H5N1 influenza virus is endemic in Southeast Asia (47) and is expanding westward. In addition, its virulence is extremely higher than other HPAI, like H7N7. Moreover, the avian host range is expanding, as species previously considered resistant, now get infected and can contribute to the dissemination of the virus. In the context of H5N1, all movements (trade, high international mobility, migration and smuggling) can become high risk factors of spreading the disease. In most European countries eradication measures are applied when an outbreak occurs. But such measures have great economical and social implications, and are no longer generally accepted. The combination of prophylactic measures (vaccination and medicines), hygienic measures and surveillance could offer an acceptable alternative.

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. In most cases, the cause of ALS is unknown although in a number of familial ALS cases mutations in the superoxide dismutase 1 (SOD1) gene were discovered. The mechanism underlying the selective motor neuron death is not yet clarified. However, it is clear that excitotoxicity could play a role in the selectivity of the motor neuron death. Excitotoxicity is the phenomenon in which the normal glutamate-mediated communication between neurons is disturbed and ultimately leads to neuronal death. In the first part of this study, we have investigated the intrinsic characteristics of motor neurons that could be responsible for the fact that these cells are extremely sensitive to excitotoxicity. Despite the fact that only the motor neurons die during ALS, it is clear that also other cell types play an important role during this process. In the second part of this study, we have concentrated on the potential role of the microglia. These cells are the macrophages of the brain and they become activated during inflammation. Using minocycline, we have inhibited the activation of the microglia and we have investigated its effect on the start of the disease and on the survival of a mouse model for ALS. Furthermore, we have investigated the cellular mechanism underlying the effect of minocycline. The goal of this research is to get insight into the mechanisms responsible for the selective motor neuron death during ALS and we hope that this information can help in the development of a therapy for this dramatic and incurable disease.

Knowledge of the present feeding habits and the impact of different information channels are mandatory for developing an appropriate feeding policy. The" Socio-Economisch Instituut (SEIN)", the "Universiteit Hasselt", and paediatricians of the Virga Jesse Hospital conducted a study on the feeding habits of young children between the age of 0 and 2 years in Flanders. This study was ordered by Kind en Gezin. Special attention was paid to breastfeeding. The study uses qualitative and quantitative methods. The qualitative research is limited to questions about breastfeeding such as which factors influence initiating, maintaining and ending breastfeeding. The quantitative research investigates through diaries the dietary composition, the eating habits and the parental educational support. Parents of young children aged 3, 6, 12 and 24 months throughout Flanders were questioned. The response rate was 71%, resulting in 2925 diaries that were analyzed. The study gives a comprehensive profile of the dietary habits of young children in the Flanders. Overall, feeding habits in these young infants seem to be appropriate. Concrete proposals to promote breastfeeding and to further improve healthy feeding habits in this age group are made.

"La raison d'être" of the epidermis, as beautifully portrayed by Kathy Madison in The Journal of Investigative Dermatology (2003;121:231-41), describes the primary function of the skin: The terminal differentiation of an initially multipotent stem cell produces a protective, semi-permeable SC that permits terrestrial life. The permeability barrier function of the SC is provided by lipid bilayers lamellae surrounding anucleated apoptotic corneocytes. This structure has been described by Peter Elias as the "bricks and mortar" model where the bricks are the cornecytes and the mortar refers to the adjoining lipids. How important is the barrier to the skin? Certain genetic defects are characterized by profound barrier abnormaities due to alterations in either stratum corneum lipid metabolism or protein components of the corneocytes, producing ichthyotic genodermatosis. In this review, the mechanisms that drive barrier formation are summarized and this in the light of our recent scientific findings and publications in the domain of epidermal structure and function.

Antiviral chemotherapy often relies on nucleoside analogues, which, once phophorylated by intracellular kinases, target viral polymerases and preclude DNA synthesis. In contrast, common antibacterial drugs are rarely related to such compounds. In this work TMPKmt, which is essential to DNA replication, was selected as a promising target for inhibitor design. Our work demonstrates that judicious and stepwise modifications of the substrate structure of TMPKmt, guided by the feedback of the enzyme assays as well as by the enzyme's X-ray structure, proved a valuable approach to produce a submicromolar inhibitor of this target enzyme. This inhibitor was also capable to inhibit bacterial growth. Perhaps more importantly, some of the reported thymidine analogues also represent valuable tools to better understand the structure and the mechanism of this intriguing enzyme.