Verhandelingen - Koninklijke Academie voor Geneeskunde van België
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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.