The physical and chemical parameters involved in the design and synthesis of biospecifically targeted nanoparticulate contrast media for magnetic resonance molecular imaging (MRMI) were explored in this pilot investigation. Latex nanoparticles 100, 400 and 900 nm in diameter were doubly derivatised, first with tomato lectin and then with gadolinium(III)-diethylenetriamine pentaacetic acid (Gd-chelates) to target them to epithelial and endothelial glycocalyceal N-glycans and to generate contrast enhancement in magnetic resonance imaging (MRI). After intravenous injection into mice, human placental cotyledons or human Vena saphena magna, contrasty images of the vascular structures were obtained in 1.5 T MRI with spatial resolution 0.1 mm in the imaging plane and 0.6 mm in the z axis, persisting >60 min and resistant to washing out by buffer rinses. Ultrastructural analysis of the nanoparticles revealed the targeting groups at the nanoparticle surfaces and the distribution of the Gd-chelates within the nanoparticles and enabled counts for use in determining relaxivity. The relaxivity values revealed were extremely high, accounting for the strong MR signals observed. Occasionally, nanoparticles larger than 100 nm were seen in close spatial association with disrupted regions of cell membrane or of collagen fibrils in the extracellular matrix. The data suggest that 100-nm nanoparticles generate adequate contrast for MRMI and cause least disruption to endothelial cell surfaces.

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The aim of this review is to summarize the existing literature on therapy and management of cerebrovascular insults in children and adolescents. As data sources, studies were identified by MEDLINE, PubMed, Cochrane Library, and relevant bibliographies for the topic "pediatric stroke." We also reviewed guidelines for "stroke in adults." As a result, pediatric stroke is underestimated. The annual incidence for all stroke entities (cerebral venous thrombosis and hemorrhagic and arterial ischemic stroke) is as high as for pediatric brain tumors, 3-15/100.000 children per year. A distinct etiology can be determined only in a minority of them. Underlying risk factors are multiple, mainly vasculopathies, congential heart diseases, coagulopathies, lipometabolic disorders, and sickle cell anemia. Current recommendations for therapy are based on adult studies, are preliminary, and discussed controversially. Antithrombotic therapy is uniformly recommended for the acute stage of pediatric stroke; no consensus exists on antiplatelet therapy with acetylsalicylic acid (ASA, aspirin) (5 mg/d), with ultra-fractionated or low-molecular-weight heparin. Thrombolysis using recombinant tissue plasminogen activator is not advised, despite the fact that current practice takes a different approach. None of the guidelines specify the duration of ASA for secondary prevention. Additional supportive therapy measures are osmotherapy and decompressive craniectomy. Oxygen in the absence of hypoxemia, intensive insulin therapy, antiepileptic drugs in the absence of clinical or electrographic seizures, corticosteroids, and GP-IIb/IIIa-receptor antagonists should not be used outside clinical trials. In conclusions, current therapeutic guidelines for pediatric stoke are still based on consensus and expert and society opinions and differ between countries. Consensus prevails on the need for acute anticoagulation using either antiplatelets or heparin. Long-term treatment with acetylsalicylic acid in all or only high-risk patients and for how long remains the subject of debate. Lifelong secondary prevention has never been investigated in children or adults. All guidelines agree that there is no indication for thrombolysis in children outside clinical trials, although clinical practice in large centers differs.

We report on a 4.5-year-old patient diagnosed with Glutaric aciduria type I (GAI), an autosomal recessive inborn error of lysine, hydroxylysine and tryptophan metabolism. Enzymatic assay in cultivated skin fibroblasts revealed complete absence of glutaryl-CoA dehydrogenase activity. All 11 Exons of the GCDH-Gen were sequenced and homozygosity for a yet undescribed mutation was identified. The patient was treated following the recently published guidelines for GA-I. Following this treatment regimen, the child developed normally without any manifest clinical crises. Our patient provides evidence that early commencement and strict adherence to treatment improves clinical outcome even in patients with complete absence of enzyme activity.