Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie最新文献

The sex ratio of mortality has important social implications but is only rarely considered. Women have lower mortality rates than men. The sex ratio of mortality is cause-specific and differs markedly between populations. Assuming that the genetic differences between the sexes are very similar between populations implies that the differences in the sex ratio cannot be explained by genetic factors. Gender differences in smoking levels exert a strong influence on the sex ratio of lung cancer, total cardiovascular and all-cause mortality. The sex ratio of mortality decreases with age. The mortality rates between the genders are highly significantly correlated (p < 0.0001) both at younger and older age classes, except for lung cancer in the 45-74 y age class. This demonstrates that identical factors influence the mortality rates of both genders, but at a lower level in women.

For most people, hymenoptera stings produce only a transient and bothersome local inflammatory reaction characterised by pain, redness and swelling. Alternatively, for those who are allergic to components of the venom, a re-sting may cause life-threatening, even fatal, reactions. In such patients correct diagnosis is an absolute prerequisite for effective management, i.e. specific venom immunotherapy (VIT) and generally consists of appropriate skin testing and quantification of venom-specific IgE-antibodies (sIgE). In spite the high efficiency of properly administered VIT, the molecular and cellular mechanisms of the desensitisation process are incompletely understood and remain subject of intense research. Besides the general principles and management of hymenoptera venom allergy, this review will focus on the current knowledge on the underlying tolerogenic mechanisms of VIT.

There are, at present, 22 compounds which have been formally approved (by the US Food and Drug Administration) for the treatment of HIV infections (AIDS). According to their point of intervention with the HIV replicative cycle, these compounds can be classified in 5 categories: (1) NRTIs (nucleoside reverse transcriptase inhibitors): azidothymidine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; (2) NtRTIs (nucleotide reverse transcriptase inhibitors): tenofovir, administered as its oral prodrug form TDF (tenofovir disoproxil fumarate); (3) NNRTIs (non-nucleoside reverse transcriptase inhibitors): nevirapine, delavirdine and efavirenz; (4) PIs (HIV protease inhibitors): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; and (5) FIs (fusion inhibitors): enfuvirtide. Starting from the drugs which are currently available for the treatment of AIDS, numerous combinations could be envisaged. Drug combinations are, in principle, aimed at obtaining synergism between the compounds (reasonably expected if they act by different mechanisms), while reducing the likelihood for drug resistance development. Such anti-HIV drug combination regimes were initiated about 10 years ago and have been generally referred to as HAART (for highly active antiretroviral therapy). While HAART originally consisted of a pill burden of twenty (or more) pills per day, this has been gradually diminished over the past few years, and, since July 2006, a all-in-one pill (Atripla) has become available, which contains three anti-HIV drugs (tenofovir disoproxil fumarate, emtricitabine and efavirenz) to be taken as a single pill only once daily. Given the information that has been acquired on the therapeutic use (efficacy, safety) of tenofovir disoproxil fumarate over the past five years, it would now seem mandatory to further consider the prophylactic use of TDF [and its combination with emtricitabine (Truvada) and/or Atripla], as a single daily pill to prevent HIV infection.

Dietary intake of long chain omega-3 poly-unsaturated fatty acids (LC n-3 PUFAs) in developed countries is low compared to recommendations. Seafood is naturally rich in LC n-3 PUFAs, vitamin D, and iodine, but is also a dietary source of heavy metals and organic pollutants. This study investigated the current intake of selected nutrients and contaminants via seafood and studied whether the recommendation for LC n-3 PUFAs could be reached through seafood consumption, without exceeding tolerable daily intakes (TDIs) of methyl mercury (MeHg) and dioxin-like compounds. Also the contribution of LC n-3 enriched margarines was assessed. On the basis of the current seafood consumption data, the simulation results predicted that the population currently does not reach an adequate intake for the three nutrients considered, at least when only seafood consumption is accounted for. This is mainly due to low frequency of seafood consumption. Regarding the contaminants, MeHg contamination in seafood assumed to be available on the Belgian market is not a major issue. In contrast, exceeding the TDI was noticed for the intake of dioxin-like compounds and this for heavy seafood consumers. Combination of regular seafood consumption (twice a week), with important contribution of fatty fish species (at least 50%), with regular consumption of EPA plus DHA enriched margarine can be advised to maximize LC n-3 PUFA intake without exceeding the TDI for dioxin-like compounds. It is important to add that no other dietary sources of dioxin-like compounds were taken into account in this assessment.

Of the 38.6 million people living with HIV/AIDS globally, almost 25 million (65%) live in sub-Saharan Africa. Preventive strategies and measures fall short, often simply because they are not available or are largely male-controlled. A preventive HIV vaccine is still far away; hence the drive to develop alternative prevention technologies, such as microbicides and oral pre-exposure prophylaxis, that could be female controlled. There are, at present, twenty-two anti-HIV drugs which have been formally licensed for clinical use in the treatment of HIV infections (AIDS): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, delavirdine, efavirenz, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, darunavir and enfuvirtide. These compounds, in combination, form the basis of HAART (highly active antiretroviral therapy), which has led to the development of a single daily pill existing of the combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz, which has to be taken orally once daily for the treatment of AIDS. Beyond development of new drugs and clinical evaluation of existing medications, several companies within the pharmaceutical industry have established innovative policies that provide HIV medications at affordable prices in the least-developed countries. Reduced pricing is not alone a solution, and thus companies are actively working in partnership with the World Health Organization and other multinational groups to address roadblocks such as complex registration and procurement systems. Even in this period of successful anti-HIV therapy via HAART, a growing number of patients is cycling through the various remaining therapeutic options and are increasingly becoming dependent of the availability of newly developed anti-HIV agents. It is of concern that existing and future therapies will have to be effective against newly evolving (including drug-resistant) HIV variants in patients who currently face many years, if not decades, of chronic anti-HIV drug treatment. In spite of continuous long-term interventions to promote safer sexual behaviour, HIV prevalence is high and still rising in many parts of the world. The face of the epidemic is now black, female, young and poor..., and female controlled methods are urgently needed. Female controlled methods such as microbicides and cervical barrier methods provide hopeful perspectives when condom use is low due to social, cultural and/or economic factors, but, after all, the oral administration of a single daily pill would seem the most convenient way to prevent HIV infection, as its protective activity may be independent of the route of viral transmission.

In two of its regular sessions, the Royal Academy for Medicine of Belgium consulted with influenza experts on the current threat of a severe pandemic outbreak, and in particular on the eventuality that this outbreak may be caused by a virus identical or related to the avian influenza virus H5N1. On the basis of this consultation, the Academy issued an advisory statement to the Belgian federal and Flemish regional Health Authorities. The Academy shares the experts' concern that the forthcoming influenza pandemic may well affect a larger part of the population than previous pandemics in 1958, 1968 and 1977. The Academy found it satisfying that the Belgian government is developing an appropriate pandemic containment plan. A primary objective of the plan is to safeguard general health care during the pandemic. Availability of staff and infrastructure and continuity of medical supplies must by all means remain intact. Therefore, employees in these sectors are an important target group of preparatory actions, in particular briefing about, and field rehearsals of the containment plan. Health care workers, elderly people and the chronically ill constitute a priority group eligible for vaccination with the antigens of the pandemic virus and for the administration of virus inhibitors. The effectiveness of antiviral treatment and prophylaxis during a pandemic is, given the lack of experience, uncertain. The fact that such remedies will be available must not create a false sense of security and must certainly not lead to reduced alertness with regard to the preparation and implementation of other measures. Panic reactions among the population must be avoided. Therefore, the population must be informed in due course about appropriate ways of conduct when a pandemic strikes, e.g. recognition of the early signs of influenza, the need to consult a general practitioner at once, the reason why being nursed at home is to be preferred to being hospitalized, etc. Indifference towards vaccination must be overcome. In the period prior to the pandemic people must be encouraged to obtain vaccination against the prevalent interpandemic virus strains. Belgium does not stand alone in the avian influenza threat and can largely benefit from participating in the current international initiatives to co-ordinate measures.

Proteins containing PDZ domains function as scaffolds for the formation and spatial confinement of large signaling complexes. They play an important role in the establishment and maintenance of cell polarity and neuronal connectivity. Therefore, they are intensively studied in the context of neurobiology and cancer. It is well established that PDZ domains are protein-interaction modules recognizing short peptide sequences generally situated at the C-terminal end of transmembrane receptors. Yet, it is not clear how those interactions are regulated. Our recent studies revealed that PDZ domains can also interact with phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal transduction, membrane trafficking, cytoskeleton remodeling, subcellular compartmentalization and nuclear processes. In particular, we established that the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important for receptor cargo recycling and syntenin-2 plays a role in the organization of nuclear PIP2. Those study cases indicate that cellular phosphoinositides might function as essential regulators of PDZ proteins. Here, we summarize and discuss our present knowledge about the occurrence, the biochemistry and the functionality of PDZ domain-lipid interactions.

Plasminogen activator inhibitor- (PAI-1) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type (t-PA) and urokinase-type plasminogen activator (u-PA). Consequently, PAI-1 plays an important role in cardiovascular diseases (mainly through inhibition of t-PA) and in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). As a member of the serpin superfamily, PAI-1 shares important structural properties with other serpins. However, PAI-1 also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-1 gathered since its discovery two decades ago. We are discussing (a) its structural properties of the protein and their subsequent relation to functional activities, (b) its role in a wide variety of (patho)physiological processes and (c) the development of monoclonal antibodies aiming to modulate pharmacologically this risk factor.

This work consists of two parts. In the first part we investigated the influence of first trimester bleeding on perinatal outcome after assisted reproductive technologies (ART) and we found that first-trimester bleeding not necessarily leads to spontaneous abortion, as in spontaneous pregnancies. On the other hand, first-trimester bleeding clearly is associated with an impaired pregnancy outcome, and as an independent risk factor for obstetrical and perinatal outcome, it should be taken into account in studies analysing pregnancy outcome after ART. The fact that the incidence of first trimester bleeding increases with the number of embryos transferred is another argument to move to single embryo transfer (SET). Next to a very effective reduction in multiple pregnancy rates, SET indeed seems to be beneficial in terms of pregnancy outcome characteristics in singleton pregnancies as well. In the second part of this work we indeed have demonstrated that mean birthweight is significantly higher in SET singletons compared with DET singletons. Also the incidence of preterm birth and low birthweight is clearly reduced when SET is compared with DET. A possible explanation for this outcome can be the 'avoidance' of vanishing twins in IVF/ICSI procedures when SET is applied, but this hypothesis needs further investigation. A more frequent application of SET in assisted reproductive technologies clinics could be an essential step to reduce differences in outcome between spontaneous and assisted reproduction children.