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1.
Hum Pathol ; 143: 42-49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052269

RESUMO

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma de Células de Transição , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Humanos , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Mama/patologia , Adenocarcinoma/patologia , RNA Mensageiro , Músculos/metabolismo , Músculos/patologia , Fator de Transcrição GATA3/metabolismo , Proteínas Repressoras/genética
2.
Mayo Clin Proc ; 98(12): 1820-1830, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38043998

RESUMO

OBJECTIVE: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM). PATIENTS AND METHODS: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models. RESULTS: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80). CONCLUSION: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates.


Assuntos
Meios de Contraste , Hipersensibilidade a Drogas , Humanos , Feminino , Meios de Contraste/efeitos adversos , Iohexol/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia
3.
Commun Biol ; 6(1): 1145, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37950055

RESUMO

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APPNL-G-F/NL-G-F mice were exposed to repeated single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, & 9 months. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for all groups. Then, mice were sacrificed, and their brains were assessed for pathology. APPNL-G-F/NL-G-F mice given multi-domain cognitive training compared to APPNL-G-F/NL-G-F control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. Additionally, multi-domain cognitive training improved anxiety in APPNL-G-F/NL-G-F mice as evidenced by measuring thigmotaxis behavior in the Morris water maze. There were mild reductions in microgliosis in the brain of APPNL-G-F/NL-G-F mice with single-domain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Camundongos , Animais , Idoso , Lactente , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Treino Cognitivo , Camundongos Transgênicos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Ansiedade/etiologia , Ansiedade/prevenção & controle , Proteínas Amiloidogênicas
4.
AJR Am J Roentgenol ; 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37791729

RESUMO

Iodinated contrast material (ICM) has revolutionized the field of diagnostic radiology through improvements in diagnostic performance and expansion in clinical indications for radiographic and CT examinations. Historically, nephrotoxicity was a feared complication of ICM use, thought to be associated with a significant risk of morbidity and mortality. Such fears often precluded use of ICM in imaging evaluations, commonly at the expense of diagnostic performance and timely diagnosis. Over the past 20 years, the nephrotoxic risk of ICM has become a topic of debate, as more recent evidence from higher-quality studies now suggest that many cases of what was considered contrast-induced acute kidney injury (CI-AKI) were likely cases of mistaken causal attribution; most of these cases represented either acute kidney injury (AKI) caused by any of myriad other known factors that can adversely affect renal function and were coincidentally present at the time of contrast media exposure (contrast-associated AKI (CA-AKI)) or a manifestation of the normal variation in renal function that increases with worsening renal function. This review discusses the current state of knowledge on CI-AKI and CA-AKI including the incidence, risk factors, outcomes, and prophylactic strategies in the identification and management of these clinical conditions.

5.
J Pers Med ; 13(6)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37373873

RESUMO

OBJECTIVE: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. MATERIALS AND METHODS: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. RESULTS: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CONCLUSION: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

6.
Front Behav Neurosci ; 17: 1187976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37358968

RESUMO

The amygdala has been implicated in a variety of functions linked to emotions. One popular view is that the amygdala modulates consolidation in other brain systems thought to be mainly involved in learning and memory processes. This series of experiments represents a further exploration into the role of the amygdala in memory modulation and consolidation. One interesting line of research has shown that drugs of abuse, like amphetamine, produce dendritic changes in select brain regions and these changes are thought to be equivalent to a usurping of normal plasticity processes. We were interested in the possibility that this modulation of plasticity processes would be dependent on interactions with the amygdala. According to the modulation view of amygdala function, amphetamine would activate modulation mechanisms in the amygdala that would alter plasticity processes in other brain regions. If the amygdala was rendered dysfunctional, these effects should not occur. Accordingly, this series of experiments evaluated the effects of extensive neurotoxic amygdala damage on amphetamine-induced dendritic changes in the nucleus accumbens and prefrontal cortex. The results showed that rats with large lesions of the amygdala showed the normal pattern of dendritic changes in these brain regions. This pattern of results suggests that the action of not all memory modulators, activated during emotional events, require the amygdala to impact memory.

7.
Nat Commun ; 14(1): 2759, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-37179348

RESUMO

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.


Assuntos
Fibrose Pulmonar , Camundongos , Animais , Humanos , Glicogênio , Metabolômica/métodos , Polissacarídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
Sci Rep ; 13(1): 7748, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173349

RESUMO

Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus-response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress.


Assuntos
COVID-19 , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Ratos , Masculino , Humanos , Animais , Roedores , Filhos Adultos , Pandemias , Cognição , Isolamento Social
9.
J Am Coll Radiol ; 20(5): 516-523, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934887

RESUMO

OBJECTIVE: To examine follow-up care in patients with a history of acute allergic-like reaction to iodinated contrast material (ICM), including subsequent imaging management, allergy consultation, and repeat ICM exposure and reactions. METHODS: All patients who had a moderate or severe acute allergic-like reaction to ICM after contrast-enhanced CT (CECT) examination from June 1, 2009, to January 1, 2022, at our institution were included. Chart review was performed to determine (1) whether subsequent imaging was not performed or was altered in these patients, (2) whether the patient underwent a subsequent CECT examination, and (3) whether the patient had an allergist consultation. RESULTS: A total of 251 patients were identified. One-third of patients (90 of 251, 36%) had at least one change to their subsequent imaging management due to their reaction, including performing an unenhanced CT (62 of 251, 25%) or MRI (22 of 251, 8.8%) instead of a CECT or not performing a CECT when otherwise clinically indicated (20 of 251, 8.0%). Patients with a prior severe reaction were more likely to have a change in management than patients with a prior moderate reaction (severe: 22 of 32 [69%] versus moderate: 68 of 219 [31%], P < .0001). Only 17 patients (6.8%) had an allergy consult for their ICM reaction. A total of 90 patients underwent 274 subsequent CECT examinations. Repeat allergic-like reactions were observed in one quarter of patients (24 of 90, 27%) and a tenth of CECT examinations (29 of 274, 11%). DISCUSSION: One-third of patients with a history of a moderate or severe allergic-like reaction to ICM had their subsequent imaging care modified due to their reaction.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Humanos , Meios de Contraste/efeitos adversos , Seguimentos , Hipersensibilidade/diagnóstico por imagem , Hipersensibilidade a Drogas/etiologia , Imageamento por Ressonância Magnética , Estudos Retrospectivos
10.
Alzheimers Res Ther ; 14(1): 143, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180883

RESUMO

BACKGROUND: An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer's disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise. METHODS: Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells. RESULTS: The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise. CONCLUSION: These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.


Assuntos
Doença de Alzheimer , Amiloidose , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ansiedade/etiologia , Encéfalo/metabolismo , Colinérgicos , Cognição , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Masculino , Camundongos , Camundongos Transgênicos , Água
11.
PLoS One ; 17(7): e0271071, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35895698

RESUMO

Covid-19 has been front and center in the global landscape since the beginning of 2020. In response, the scientific field has dedicated enormous amounts of resources to researching the virus and its effects. The number of times Covid-19 publications are being cited throughout the literature appears remarkably high but has not been directly compared to non-Covid-19 papers in the same journals over an extended period. In our study, we use Clarivate's Web of Science-Science Citation Index Expanded™ database to identify Covid-19 papers published in 24 major scientific journals over a period of 24 months from January 1, 2020 to December 31, 2021. We conduct our search using keywords "Covid-19", "coronavirus", and "sars-cov-2" to locate publications with these words in the title. We then quantify the number of citations these papers have received and compare rates to non-Covid-19 papers in the same journals over the same timeframe. We find that, across 24 open-access and subscription-based scientific journals, Covid-19 papers published in the past 2 years currently have a median citation rate of 120.79 compared to 21.63 for non-Covid-19 papers. When negative binomial regression is used to minimize the influence of other variables such as article number variation and field of research, Covid-19 papers have still experienced more than 80% increase in citations relative to non-Covid-19 papers. These novel findings demonstrate that Covid-19 papers are being cited at remarkably higher rates than non-Covid-19 articles contained within the same journals. This suggests that journal impact factor, which is a product of the number of citations that recently published articles receive, will likely be drastically influenced by the number of Covid-19 papers that a journal has included within its pages in the previous years.


Assuntos
COVID-19 , Publicações Periódicas como Assunto , COVID-19/epidemiologia , Bases de Dados Factuais , Humanos , Fator de Impacto de Revistas , Publicações
15.
Adv Cancer Res ; 154: 227-251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35459471

RESUMO

The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment.


Assuntos
Neoplasias Pulmonares , Análise por Conglomerados , Humanos , Polissacarídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Microambiente Tumoral
16.
Behav Brain Res ; 423: 113790, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35149121

RESUMO

Evidence from genetic, behavioural, anatomical, and physiological study suggests that the hippocampus functionally differs across its longitudinal (dorsoventral or septotemporal) axis. Although, how to best characterize functional and representational differences in the hippocampus across its long axis remains unclear. While some suggest that the hippocampus can be divided into dorsal and ventral subregions that support distinct cognitive functions, others posit that these regions vary in their granularity of representation, wherein spatial-temporal resolution decreases in the ventral (temporal) direction. Importantly, the cognitive and granular hypotheses also make distinct predictions on cellular recruitment dynamics under conditions when animals perform tasks with qualitatively different cognitive-behavioural demands. One interpretation of the cognitive function account implies that dorsal and ventral cellular recruitment differs depending on relevant behavioural demands, while the granularity account suggests similar recruitment dynamics regardless of the nature of the task performed. Here, we quantified cellular recruitment with the immediate early gene (IEG) Arc across the entire longitudinal CA1 axis in female and male rats performing spatial- and fear-guided memory tasks. Our results show that recruitment is greater in dorsal than ventral CA1 regardless of task or sex, and thus support a granular view of hippocampal function across the long axis. We further discuss how future experiments might determine the relative contributions of cognitive function and granularity of representation to neuronal activity dynamics in hippocampal circuits.


Assuntos
Comportamento Animal/fisiologia , Região CA1 Hipocampal/metabolismo , Proteínas do Citoesqueleto/metabolismo , Aprendizagem/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Feminino , Masculino , Ratos , Ratos Long-Evans , Caracteres Sexuais , Análise e Desempenho de Tarefas
17.
Radiology ; 302(2): 270-273, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34783590

RESUMO

In this article, members of the American College of Radiology Committee on Drugs and Contrast Media propose a new term for symptoms reported after intravascular exposure to gadolinium-based contrast agents-Symptoms Associated with Gadolinium Exposure, or SAGE. This term is advocated in lieu of other proposed nomenclature that presumes a causal relationship that has not yet been scientifically verified. The purpose of this new term, SAGE, is to assist researchers and clinical providers in describing such symptoms without prematurely causally attributing them to a disease and to standardize reporting of these symptoms to allow for coherent interpretation of related studies.


Assuntos
Meios de Contraste/efeitos adversos , Hipersensibilidade a Drogas/classificação , Hipersensibilidade a Drogas/etiologia , Gadolínio/efeitos adversos , Humanos , Sociedades Médicas , Terminologia como Assunto , Estados Unidos
18.
Radiology ; 302(3): 676-683, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34931861

RESUMO

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.


Assuntos
Encéfalo/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Administração Intravenosa , Animais , Encéfalo/metabolismo , Meios de Contraste/metabolismo , Gadolínio/metabolismo , Masculino , Modelos Animais , Ratos , Ratos Wistar
19.
Radiology ; 301(1): 133-140, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34342504

RESUMO

Background It is unclear whether steroid premedication is an effective means of preventing repeat allergic-like reactions in high-risk patients with a previous allergic-like reaction to iodinated contrast material (ICM). Purpose To compare the effectiveness of ICM substitution (ie, using iohexol in a patient with a previous iopromide reaction) with 12- and 2-hour steroid premedication for preventing repeat acute allergic-like reactions in high-risk patients. Materials and Methods This retrospective study identified all high-risk (ie, having a previous allergic-like reaction) adult and pediatric patients who underwent a contrast-enhanced CT examination at the institution from June 1, 2009, to May 9, 2017. Prophylactic treatments and repeat reactions were identified using chart review. The effectiveness of prophylactic treatments on repeat reaction rates was examined with multivariable regression models that used generalized estimating equations. Results A total of 1973 high-risk patients who underwent 4360 subsequent ICM-enhanced CT examinations were included. Of the 4360 examinations, a total of 280 allergic-like reactions occurred (6%) in 224 of the 1973 patients (11% of patients), with only 19 of 280 reactions (7%) that were more severe than the previous reaction being demonstrated. After adjustment, patients who received a different ICM with and without steroid premedication had a significantly lower rate of repeat reactions than did patients who received steroid premedication and the same ICM (same ICM and steroid premedication: 80 of 423 examinations [19%]; different ICM and no steroid premedication: 10 of 322 examinations [3%]; odds ratio [OR], 0.14 [95% CI: 0.06, 0.33]; P < .001; different ICM and steroid premedication: five of 166 patients [3%]; OR, 0.12 [95% CI: 0.04, 0.36]; P < .001). When examining the first scan only, patients who received the same ICM had a similar risk of repeat reactions regardless of whether they received steroid premedication (steroid premedication: 44 of 172 patients [26%] vs no premedication: 73 of 298 patients [25%]; OR, 1.00 [95% CI: 0.64, 1.57]; P = .99). Conclusion In this cohort, using an iodinated contrast material (ICM) substitution was more effective for preventing repeat allergic-like reactions than using steroid premedication and the same ICM that caused the previous reaction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Davenport and Weinstein in this issue.


Assuntos
Corticosteroides/uso terapêutico , Meios de Contraste/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Meios de Contraste/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Eur J Neurosci ; 54(8): 6740-6761, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34214189

RESUMO

The hippocampus plays a critical role in spatial learning and memory. Its contribution to support these kinds of learning and memory functions relies on synaptic plasticity and related molecular mechanisms, well documented in the long-term potentiation (LTP) literature. The present experiment measures AMPA subunit expression, in a ratio of GluA2:GluA1 as an indicator of plasticity across the hippocampus, in rats that underwent new spatial learning in either a familiar or novel context. Statistically significant effects in this plasticity indicator were observed of context condition, time after task and hippocampal subfield. Based on the strong inputs of entorhinal cortex to hippocampus, we also identified differences in GluA2:GluA1 expression trends between time points and room conditions that mirror trends in medial and lateral entorhinal cortex connectivity between new room and same room context learning, respectively. Across the transverse axis in infrapyramidal dentate gyrus, CA3 and CA1, plasticity followed entorhinal cortex projection patterns. Along the transverse axis in the suprapyramidal blade of the dentate gyrus, and along the long axis in dentate gyrus and CA3, results did not follow entorhinal cortex subregion projection patterns. These latter results may be indicative of pattern separation in the dentate gyrus and emotional triage functions of the ventral hippocampus.


Assuntos
Via Perfurante , Receptores de AMPA , Animais , Giro Denteado , Hipocampo , Ratos , Aprendizagem Espacial
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