56 research outputs found
Propylthiouracil Is Teratogenic in Murine Embryos
Background: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods: We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results: When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss o
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DEVELOPMENT OF A CERAMIC TAMPER INDICATING SEAL: SRNL CONTRIBUTIONS
Savannah River National Laboratory (SRNL) and Sandia National Laboratories (SNL) are collaborating on development of a Ceramic Seal, also sometimes designated the Intrinsically Tamper Indicating Ceramic Seal (ITICS), which is a tamper indicating seal for international safeguards applications. The Ceramic Seal is designed to be a replacement for metal loop seals that are currently used by the IAEA and other safeguards organizations. The Ceramic Seal has numerous features that enhance the security of the seal, including a frangible ceramic body, protective and tamper indicating coatings, an intrinsic unique identifier using Laser Surface Authentication, electronics incorporated into the seal that provide cryptographic seal authentication, and user-friendly seal wire capture. A second generation prototype of the seal is currently under development whose seal body is of Low Temperature Co-fired Ceramic (LTCC) construction. SRNL has developed the mechanical design of the seal in an iterative process incorporating comments from the SNL vulnerability review team. SRNL is developing fluorescent tamper indicating coatings, with recent development focusing on optimizing the durability of the coatings and working with a vendor to develop a method to apply coatings on a 3-D surface. SRNL performed a study on the effects of radiation on the electronics of the seal and possible radiation shielding techniques to minimize the effects. SRNL is also investigating implementation of Laser Surface Authentication (LSA) as a means of unique identification of each seal and the effects of the surface coatings on the LSA signature
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Abstract WMP16: Radiographic Characteristics of Mild Ischemic Stroke Patients With Visible Intracranial Occlusion; Data From the INTERRSeCT Multi-Center Prospective Imaging Study
Background:
Early neurological deterioration occurs in one third of mild ischemic strokes primarily due to the presence of a visible intracranial vessel occlusion. We studied the clinical and vascular occlusive patterns, thrombus characteristics and recanalization rates in patients with mild ischemic stroke and a visible intracranial vessel occlusion.
Methods:
We studied patients enrolled in the INTERRSeCT multi-center prospective study of acute ischemic strokes with visible intracranial occlusions. We compared the clinical, thrombus characteristics and recanalization rates between two groups, 1) mild ischemic NIHSS≤5 and 2) moderate/severe strokes NIHSS >5, with or without IV alteplase treatment. Vessel imaging with CT angiography (CTA) was initiated within 12 hrs of symptom onset followed by repeat imaging with CTA or cerebral angiogram (before endovascular therapy; EVT) within 4 +/- 2 hrs.
Results:
Among 575 patients with a visible intracranial occlusion, 12.9% had mild strokes with similar patient characteristics compared to the moderate/severe stroke group. Residual flow grades were similar between the two groups (residual flow grades I-II, 21% vs 19%). The mild stroke group had longer symptom-onset-to -CT (240 vs 167 min, p=0.02) and -CTA (246 vs 172 min, p=0.02) times, longer CT to needle time (35 vs 26 min, p<0.01), more distal occlusions (49% in M2 of the middle cerebral artery), lower clot burden scores 9 (6-9) vs 6 (4-9) (p<0.001), better collateral flow (9.1 vs 7.6, p=0.001) and no association between residual flow grade and recanalization. The mild stroke group was less likely to receive IV alteplase (62% vs 84%), but more likely to recanalize (rAOL2b and 3) with (46% vs 29%) and without (38% vs 26%) IV alteplase.
Conclusion:
Some thrombus characteristics that predict recanalization in more severe strokes do not predict recanalization in mild strokes, such as residual blood flow through intracranial occlusions, though they have similar cardiovascular risk factors. Less than half of patients with mild strokes recanalized with IV alteplase which was associated with longer decision-making times suggesting that more aggressive use of thrombolytics and/or EVT may be viable treatment options in this population
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