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11.
《Biomaterials》2015
Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity. 相似文献
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13.
Victoria A. Chang Dawn M. Meyer Brett C. Meyer 《Journal of stroke and cerebrovascular diseases》2019,28(1):163-166
Background
Acute stroke codes may be activated for anisocoria, but how often these codes lead to a final stroke diagnosis or alteplase treatment is unknown. The purpose of this study was to assess the frequency of anisocoria in stroke codes that ultimately resulted in alteplase administration.Methods
We retrospectively assessed consecutive alteplase-treated patients from a prospectively-collected stroke registry between February 2015 and July 2018. Based on the stroke code exam, patients were categorized as having isolated anisocoria [A+(only)], anisocoria with other findings [A+(other)], or no anisocoria [A?]. Baseline demographics, stroke severity, alteplase time metrics, and outcomes were also collected.Results
Ninety-six patients received alteplase during the study period. Of the 94 who met inclusion criteria, there were 0 cases of A+(only). There were 9 cases of A+(other) (9.6%). A+(other) exhibited higher baseline National Institutes of Health (NIH) Stroke Scale scores compared to A? (17 versus 7; P?=?.0003), and no additional differences in demographics or alteplase time metrics. Final stroke diagnosis and other outcome measures were no different between A+(other) and A?. Of the A+ patients without pre-existing anisocoria, 5 of 6 (83%) had posterior circulation events or diffuse subarachnoid hemorrhage.Conclusions
In this exploratory analysis, zero patients with isolated anisocoria received alteplase treatment. Anisocoria as a part of the neurologic presentation occurred in 10% of alteplase patients, and was strongly associated with a posterior circulation event. Therefore, we conclude that anisocoria has a higher likelihood of leading to alteplase treatment when identified in the presence of other neurologic deficits. 相似文献14.
Gudrun Aspelund Elaa M Mahdi David H Rothstein Derek S Wakeman 《Journal of gastroenterology and hepatology》2019,34(6):966-974
Choledochal cysts (CDCs) and biliary atresia (BA) are rare pediatric hepatobiliary anomalies that require surgical intervention due to increased risk of malignancy and liver failure, respectively. The underlying disease and operative procedures place patients at risk for long‐term complications, which may continue to affect them into adulthood. Lack of a transitional care model in the health‐care system potentiates the challenges they will face following aging out of their pediatric providers' care. We sought to elucidate the long‐term complications and challenges patients with CDCs and BA face, review the current literature regarding transitioning care, and propose guidelines aiding adult providers in continued care and surveillance of these patients. A literature review was performed to assess short‐term and long‐term complications after surgery and the current standards for transitioning care in patients with a history of CDCs and BA. While transitional programs exist for patients with other gastrointestinal diseases, there are few that focus on CDCs or BA. Generally, authors encourage medical record transmission from pediatric to adult providers, ensuring accuracy of information and compliance with treatment plans. Patients with CDCs are at risk for developing biliary malignancies, cholangitis, and anastomotic strictures after resection. Patients with BA develop progressive liver failure, necessitating transplantation. There are no consensus guidelines regarding timing of follow up for these patients. Based on the best available evidence, we propose a schema for long‐term surveillance. 相似文献
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16.
BackgroundPre-operative carbohydrate (CHO) drinks have shown some benefits peri-operatively and have been incorporated into many Enhanced Recovery after Surgery (ERAS) programmes. We assessed the gastric emptying of pre-operative CHO drinks prior to elective caesarean delivery using ultrasonography.MethodsAfter a standard overnight fast, non-labouring pregnant women awaiting elective caesarean delivery underwent a standardised gastric ultrasound assessment at baseline and then every 20 min for 2 h after consuming 400 mL of a CHO drink. The gastric emptying was determined at each time-point both qualitatively and quantitatively. The primary outcome was the time taken for participants to return to a qualitative fasted Perlas grade of 0 or 1.ResultsThe gastric emptying of 40 participants was analysed. At baseline, all patients had a qualitative grade of either 0 or 1. All patients had returned to either grade 0 or 1 by 100 min. At 120 min the antral right lateral decubitus (RLD) cross-sectional area (CSA) was 8.03 cm2 (95th percentile; 95% CI 7.4 to 8.3 cm2) and gastric volume per kg was 1.57 mL/kg (95th percentile; 95% CI 1.4 to 2.2). At 120 min there was no statistically significant difference from baseline for the RLD CSA (P=0.38) or gastric volume per kg (P=0.27).ConclusionsThe gastric emptying of this cohort of pregnant women suggests that 400 mL of a CHO drink can be safely consumed up to two hours before elective surgery. This study can help inform future peri-operative fasting guidelines for pregnant patients. 相似文献
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18.
Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases. 相似文献
19.
Michael A. Gibney David Fitz-Patrick David C. Klonoff Shahista Whooley Betty Lu Wen Yue 《Current medical research and opinion》2020,36(10):1591-1600
Abstract
Objective
Two similarly designed studies compared user experiences with a second-generation extra-thin-wall, 5-bevel 32?G?×?4?mm pen needle (PN) with redesigned hub versus four thinner commercially available PNs. 相似文献20.
Rebecca Carman Lesley Andrew Amanda Devine Jacques Oosthuizen 《Australian and New Zealand journal of public health》2019,43(6):563-569
Objective: To identify behavioural barriers of service provision within general practice that may be impacting the vaccination coverage rates of Aboriginal children in Perth, Western Australia (WA). Methods: A purposive developed survey was distributed to 316 general practices across Perth and three key informant interviews were conducted using a mixed‐methods approach. Results: Of the surveyed participants (n=101), 67.4% were unaware of the low vaccination coverage in Aboriginal children; 64.8% had not received cultural sensitivity training in their workplace and 46.8% reported having inadequate time to follow up overdue child vaccinations. Opportunistic vaccination was not routinely performed by 30.8% of participants. Key themes identified in the interviews were awareness, inclusion and cultural safety. Conclusion: Inadequate awareness of the current rates, in association with a lack of cultural safety training, follow‐up and opportunistic practice, may be preventing greater vaccination uptake in Aboriginal children in Perth. Cultural safety is a critical component of the acceptability and accessibility of services; lack of awareness may restrict the development of strategies designed to equitably address low coverage. Implications: The findings of this study provide an opportunity to raise awareness among clinicians in general practice and inform future strategies to equitably deliver targeted vaccination services to Aboriginal children. 相似文献