[The Dutch Thrombosis Service and its problems. From the Thrombosis Service in Leiden].
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This concluding section of the series will evaluate the role of host environment in the development of thromboembolism (TE) in children with acute lymphoblastic leukemia (ALL). The available evidence suggests that TE in association with childhood ALL is a multifactorial entity resulting from the interaction of the disease, chemotherapy and its effects, and possible prothrombotic states inherent to the host. The few studies conducted so far in children with ALL have reported wide variability in the prevalence of prothrombotic defects and its impact on the risk of TE. The prevalence of prothrombotic defects varies in different ethnic population. Since different ALL therapy studies use different chemotherapeutic agents in various dosage and combination, it is important that every major study group assesses the risk of TE, including the prevalence of prothrombotic defects, within their therapy plan. This will help to identify the population at risk for TE and for thromboprophylaxis, if indicated.
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The authors have developed a liquid material for thrombosing aneurysms. This material is a mixture of cellulose acetate polymer and bismuth trioxide dissolved in dimethyl sulfoxide. On contact with blood, the dimethyl sulfoxide diffuses and cellulose acetate polymer forms, which balloons when slowly injected into the blood. The polymer solidifies from surface to core in 5 minutes. Cellulose acetate polymer was injected directly into experimental aneurysms created in 10 dogs; it rapidly hardened in the shape of the aneurysms, completely obliterating them but preserving the parent vessels in all cases. No distal migration of the polymer was seen. The good results of this experimental trial led to a clinical study using a cellulose acetate polymer, as described in Part II.
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Small animal models have several advantageous characteristics, but those used in preclinical restenosis research have lacked efficacy in predicting the success of interventions to inhibit restenosis in humans. Large animal models have been more successful than small animal models in predicting efficacy of interventions to inhibit restenosis in humans, but the results of studies carried out with these models have not been uniformly predictive. Confirmation of the results of small animal studies in large animals has not always yielded information predictive of success in humans; however, the absence of such confirmation has had strong negative predictive value. Small animal models used for evaluation of interventions to inhibit luminal narrowing following arterial instrumentation have failed to closely simulate human atherosclerosis and the stenotic lesions subjected to instrumentation in humans. Transgenic, atherosclerotic animals hold promise for the development of more useful small animal models to study mechanisms of the response of diseased arteries to angioplasty and stents. The pig has been the most useful large animal to study stenosis/ restenosis, but more information is needed to overcome the limitations of this model.
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