RESUMEN
OBJECTIVE: Status epilepticus (SE) is frequently associated with peri-ictal magnetic resonance imaging (MRI) abnormalities (PMA). However, the anatomical distribution of these alterations has not been systematically studied. The aim of this study was to assess the localization patterns of PMA in patients with SE. METHODS: In this prospective case-control study, we compared the distribution and combinations of diffusion-restricted PMA to diffusion-restricted lesions caused by other neurological conditions. All patients of the SE group and the control group underwent MRI including a diffusion-weighted imaging sequence. Patients with SE were imaged within 48 h after its onset. RESULTS: We enrolled 201 patients (51 with SE and 150 controls). The most frequent locations of PMA in SE were cortex (25/51, 49%), followed by hippocampus (20/51, 39%) and pulvinar of thalamus (10/51, 20%). In the control group, the cortex was involved in 80 of 150 (53%), white matter in 53 of 150 (35%), and basal ganglia in 33 of 150 (22%). In the control group, the pulvinar of thalamus was never affected and hippocampal structures were rarely involved (7/150, 5%). Involvement of the pulvinar of thalamus and the hippocampus had high specificity for SE at 100% (95% confidence interval [CI] = 98-100) and 95% (95% CI = 91-98), respectively. The sensitivity, however, was low for both locations (pulvinar of thalamus: 20%, 95% CI = 10-33; hippocampus: 39%, 95% CI = 26-54). SIGNIFICANCE: Diffusion-restricted MRI lesions observed in the pulvinar of thalamus and hippocampus are strongly associated with SE. These changes may help physicians in diagnosing SE-related changes on MRI in an acute setting, especially in cases of equivocal clinical and electroencephalographic manifestations of SE.
Asunto(s)
Imagen por Resonancia Magnética , Estado Epiléptico , Humanos , Estado Epiléptico/diagnóstico por imagen , Estudios de Casos y Controles , Masculino , Femenino , Persona de Mediana Edad , Adulto , Imagen por Resonancia Magnética/métodos , Anciano , Estudios Prospectivos , Adulto Joven , Adolescente , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , NiñoRESUMEN
PURPOSE: Polysorbates are among the most used surfactants in biopharmaceutical products containing proteins. Our work aims to develop a high-throughput fluorometric assay to further diversify the analytical toolbox for quantification of PSs. METHOD: The assay leverages the micelle activated fluorescence signal from N-Phenyl-1-Naphthylamine (NPN). The development and optimization of assay parameters were guided by the pre-defined analytical target profile. Furthermore, NMR was used to probe the interaction between protein, PS80 and NPN in the measurement system and understand protein interference. RESULTS: All assay parameters including excitation and emission wavelengths, standard curve, NPN concentration, and incubation time have been optimized and adapted to a microplate format, making it compatible with automated solutions that will be pursued in the near future to drive consistency and efficiency in our workflows. The specificity, accuracy, and precision of the assay have been demonstrated through a case study. Furthermore, NMR results provided additional insight into the change of the interaction dynamics between PS80 and NPN as the protein concentration increases. The results indicate minimal interaction between the protein and PS80 at lower concentration. However, when the concentration exceeds 75 mg/mL, there is a significant interaction between the protein and PS-80 micelle and monomer. CONCLUSION: A high-throughput fluorometric assay has been developed for quantification of polysorbates in biopharmaceutical samples including in-process samples, drug substance and drug product. The assay reported herein could serve as a powerful analytical tool for polysorbate quantification and control, complementing the widely used liquid chromatography with charged aerosol detection method.
Asunto(s)
Colorantes Fluorescentes , Fluorometría , Ensayos Analíticos de Alto Rendimiento , Micelas , Polisorbatos , Polisorbatos/química , Polisorbatos/análisis , Colorantes Fluorescentes/química , Ensayos Analíticos de Alto Rendimiento/métodos , Fluorometría/métodos , Tensoactivos/química , Tensoactivos/análisis , 1-Naftilamina/análogos & derivados , 1-Naftilamina/química , Productos Biológicos/análisis , Productos Biológicos/química , Espectroscopía de Resonancia Magnética/métodosRESUMEN
ABSTRACT: This study examined 71 cases, where 45 cases were equine-related and 26 were bovine-related. Data for this study were collected by examining cases between 2000 and 2022 from the Oklahoma Office of the Chief Medical Examiner database.A majority of the equine-related fatality cases involved males aged 0 to 18 and 60 to 69 years, with sustained injuries of the head, neck, and thoracic regions while being mounted. These injuries were most often inflicted by being kicked or resulted from blunt force of impact. A majority of the bovine-related fatality cases involved males aged 60 to 79 years, with sustained injuries of the head, neck, and thoracic regions while being unmounted. These injuries were most often inflicted by being butted, trampled, or resulted from blunt force of impact. Of the total cases, approximately 42% of the causes of death were blunt force trauma of the head/neck and nearly 34% were multiple blunt force injuries. Only 3 mechanisms of death were discussed.There are distinct similarities in the most prominent gender, cause of sustained injury, and location of injury between equine- and bovine-related fatalities in Oklahoma. This study lends significant support to the need for increased awareness of safe handling practices and safety precaution education for both equine and bovine activities.