Verhandelingen - Koninklijke Academie voor Geneeskunde van België
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Verh. K. Acad. Geneeskd. Belg. · Jan 2000
ReviewThe role of beta 2-glycoprotein I-dependent lupus anticoagulants in the pathogenesis of the antiphospholipid syndrome.
The antiphospholipid syndrome (APS) is defined as the association of antiphospholipid antibodies (aPL) with arterial or venous thrombosis, recurrent fetal loss, thrombocytopenia or neurologic disorders. Some aPL can be detected via phospholipid dependent coagulation assays where they present as an aspecific coagulation inhibitor termed the lupus anticoagulant (LA). Other antibodies can be measured via immunological assays mostly via their capability to bind to immobilised cardiolipin and are therefore called anticardiolipin antibodies (aCL). ⋯ Further studies also showed that our LA positive anti-beta 2GPI moabs have a potential for the production of LA control specimens, that could be made available to routine hemostasis laboratories to assess intra-laboratory precision of LA testing, to manufacturers to produce highly sensitive assay systems and to control batch-to-batch variability of their reagents and to organizations involved in external quality assessment. In conclusion this work has enabled us to understand the molecular mechanism by which certain autoimmune antibodies found in patients with APS prolong coagulation assays in vitro. The antibodies generated are an important tool to improve the laboratory diagnosis of the lupus anticoagulant and may help us clarify the pathogenic role of autoimmune anti-beta 2GPI antibodies.
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Verh. K. Acad. Geneeskd. Belg. · Jan 2000
Review[Animal experiments: legal, scientific and ethical aspects].
Among the legal aspects the following topics are treated: the definitions of an experimental animal, an animal experiment and alternative methods with special reference to the 3 R's (replacement, reduction and refinement of animal experiments); the qualifications, education and training of researchers and animal technicians; the licence for animal experimentation; the control on animal welfare; the origin and identification of experimental animals; statistical data on the number of experimental animals; ethics committees and their structure and functions in The Netherlands and Flanders. Extrapolation, species specificity and variability are the most important scientific limitations of animal experimentation. After a short historical survey on the man-animal relation, the following ethical aspects are discussed: the instrumental versus intrinsic value of an experimental animal; the hybrid status of the animal; the objectives of animal rights movements; the balance between the human benefit of an animal experiment and the discomfort for the animal; the problem of animal rights and animal suffering and pain.
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Verh. K. Acad. Geneeskd. Belg. · Jan 1999
Review[Chronic asthma: current policy and therapeutic possibilities in the future].
Asthma is a chronic disease with an important and increasing prevalence. The objective of the treatment of asthma is control of the disease. For most patients with chronic asthma this means the regular use of controller medication. ⋯ Many new drugs for the treatment of asthma are currently in development. They either focus on recently discovered pathogenic mechanisms or try to improve existing anti-asthma drugs. There is the distinct hope that cure of asthma might become an achievable goal.
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Verh. K. Acad. Geneeskd. Belg. · Jan 1998
ReviewAcute and prolonged critical illness are two distinct neuroendocrine paradigms.
Acute and prolonged critical illness are different metabolic and neuroendocrine paradigms and should perhaps be approached with different therapeutic strategies. The initial endocrine response consists primarily of an activated release of anterior pituitary hormones and peripheral inactivation of anabolic pathways, thought to provide substrates for survival while anabolism is postponed and to activate the immune cascade while the host is being protected against deleterious effects of the latter. There is still no solid basis for hormonal intervention in the acute phase of illness. ⋯ We demonstrated that selected pituitary-dependent axes can be reactivated in the chronic phase of critical illness, with preserved peripheral responsiveness. Intervening at the hypothalamic-pituitary level appears to be a safer strategy compared to administration of peripheral hormones, as presence of active feed-back inhibition prevents overtreatment on an individual basis at a time when it is difficult--if not impossible--to determine what is a "normal" or "optimal" level of circulating peripheral hormones. Whether this novel endocrine strategy will result in beneficial metabolic effects and, ultimately, will stimulate the recovery process in those patients who need it most, remains to be elucidated.
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Verh. K. Acad. Geneeskd. Belg. · Jan 1997
ReviewPlatelet-vessel wall interactions in thrombosis and restenosis role of von Willebrand factor.
As a consequence of vessel wall injury, subendothelial matrix and collagen fibers are exposed to the flowing blood. Circulating platelets adhere to these structures and initiate arrest of blood flow. Subendothelial von Willebrand Factor (vWF) plays an important role in mediating platelet adhesion to the injured site, at least in the arterial circulation, characterized by sufficiently elevated shear forces to allow a critical conformation change in vWF, enabling an interaction between the vWF domain A1 and the vWF receptor on the platelet, the GPIb/IX complex. ⋯ In vivo anti-thrombotic studies in the hamster showed that the vWF antagonist aurin tricarboxylc acid was a more potent inhibitor of arterial thrombosis than of venous thrombosis, confirming the in vivo role of vWF during thrombus formation. Following vessel wall damage and thrombus formation, the neointima that formed in the hamster carotid artery developed more rapidly than in other models, and its formation partially responded to reported inhibitors of restenosis. The combination of cardiovascular drugs with complementary modes of action, such as G4120 (inhibitor of platelet GPIIb/IIIa and smooth muscle cell alpha(v) beta(3)) and quinapril (potent vascular ACE inhibitor) prevented neointima formation to about 70%, i.e. better than with any treatment separately.