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1.
Clin Infect Dis ; 74(3): 427-436, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33956972

RESUMO

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.


Assuntos
Doenças Autoimunes , COVID-19 , Doenças Autoimunes/epidemiologia , Teste para COVID-19 , Humanos , Pandemias , Fatores de Risco , SARS-CoV-2
2.
Phys Rev Lett ; 127(26): 262502, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35029460

RESUMO

^{18}Mg was observed, for the first time, by the invariant-mass reconstruction of ^{14}O+4p events. The ground-state decay energy and width are E_{T}=4.865(34) MeV and Γ=115(100) keV, respectively. The observed momentum correlations between the five particles are consistent with two sequential steps of prompt 2p decay passing through the ground state of ^{16}Ne. The invariant-mass spectrum also provides evidence for an excited state at an excitation energy of 1.84(14) MeV, which is likely the first excited 2^{+} state. As this energy exceeds that for the 2^{+} state in ^{20}Mg, this observation provides an argument for the demise of the N=8 shell closure in nuclei far from stability. However, in open systems this classical argument for shell strength is compromised by Thomas-Ehrman shifts.

3.
Phys Rev Lett ; 126(16): 162701, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33961456

RESUMO

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

4.
Semin Neurol ; 41(6): 673-685, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34826871

RESUMO

Facial palsy is a common neurologic concern and is the most common cranial neuropathy. The facial nerve contains motor, parasympathetic, and special sensory functions. The most common form of facial palsy is idiopathic (Bell's palsy). A classic presentation requires no further diagnostic measures, and generally improves with a course of corticosteroid and antiviral therapy. If the presentation is atypical, or concerning features are present, additional studies such as brain imaging and cerebrospinal fluid analysis may be indicated. Many conditions may present with facial weakness, either in isolation or with other neurologic signs (e.g., multiple cranial neuropathies). The most important ones to recognize include infections (Ramsay-Hunt syndrome associated with herpes zoster oticus, Lyme neuroborreliosis, and complications of otitis media and mastoiditis), inflammatory (demyelination, sarcoidosis, Miller-Fisher variant of Guillain-Barré syndrome), and neoplastic. No matter the cause, individuals may be at risk for corneal injury, and, if so, should have appropriate eye protection. Synkinesis may be a bothersome residual phenomenon in some individuals, but it has a variety of treatment options including neuromuscular re-education and rehabilitation, botulinum toxin chemodenervation, and surgical intervention.


Assuntos
Paralisia de Bell , Paralisia Facial , Herpes Zoster da Orelha Externa , Neuroborreliose de Lyme , Corticosteroides , Paralisia de Bell/diagnóstico , Paralisia de Bell/tratamento farmacológico , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Paralisia Facial/terapia , Humanos
5.
J Exp Bot ; 71(20): 6612-6622, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-32793967

RESUMO

Systemic acquired resistance (SAR) is an inducible defense mechanism that systemically enhances resistance against pathogens in foliar tissues. SAR, which engages salicylic acid (SA) signaling, shares molecular components with the autonomous pathway, which is involved in controlling flowering time in Arabidopsis thaliana. FLOWERING LOCUS D (FLD) is one such autonomous pathway component that is required for flowering time and the systemic accumulation of SA during SAR. Here, we show that CYP720A1, a putative cytochrome P450 monoxygenase, controls FLD expression and is required for the timing of flowering and the manifestation of SAR. The delayed flowering time in the cyp720a1 mutant correlated with the elevated transcript level of the floral repressor FLC, while the SAR deficiency phenotype of the cyp720a1 mutant correlated with the inability to systemically accumulate SA. CYP720A1 transcript abundance in shoots is poor compared with roots. Reciprocal root-shoot grafting confirmed that CYP720A1 function in the roots is critical for flowering time and SAR. We therefore suggest that root to shoot communication involving a CYP720A1-dependent factor contributes to the timing of reproductive development and defense in the foliage.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Imunidade Inata , Proteínas de Domínio MADS/genética , Ácido Salicílico
6.
J Exp Bot ; 71(16): 4903-4913, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32392578

RESUMO

Abietane diterpenoids are tricyclic diterpenes whose biological functions in angiosperms are largely unknown. Here, we show that dehydroabietinal (DA) fosters transition from the vegetative phase to reproductive development in Arabidopsis thaliana by promoting flowering time. DA's promotion of flowering time was mediated through up-regulation of the autonomous pathway genes FLOWERING LOCUS D (FLD), RELATIVE OF EARLY FLOWERING 6 (REF6), and FVE, which repress expression of FLOWERING LOCUS C (FLC), a negative regulator of the key floral integrator FLOWERING LOCUS T (FT). Our results further indicate that FLD, REF6, and FVE are also required for systemic acquired resistance (SAR), an inducible defense mechanism that is also activated by DA. However, unlike flowering time, FT was not required for DA-induced SAR. Conversely, salicylic acid, which is essential for the manifestation of SAR, was not required for the DA-promoted flowering time. Thus, although the autonomous pathway genes FLD, REF6, and FVE are involved in SAR and flowering time, these biological processes are not interdependent. We suggest that SAR and flowering time signaling pathways bifurcate at a step downstream of FLD, REF6, and FVE, with an FLC-dependent arm controlling flowering time, and an FLC-independent pathway controlling SAR.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Abietanos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Mutação , Fatores de Transcrição
7.
Fish Shellfish Immunol ; 103: 472-480, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439514

RESUMO

Recent studies have utilized the fathead minnow (Pimephales promelas) to explore the immunotoxic effects associated with a variety of environmental contaminants in the absence of immunological stimuli. Though this approach allows for alterations in the resting immune system to be detected, previous evidence suggests that many immunotoxic effects may only manifest in the activated immune system. However, basic immune responses to pathogens have not been well described in this species. To expand the utility of the fathead minnow as a model for immunotoxicity testing, a more comprehensive understanding of the activated immune system is required. As such, the main goal of this study was to characterize the transcriptomic response to pathogen infection in the fathead minnow using RNA sequencing. To achieve this goal, female fathead minnows were intraperitoneally injected with either Hank's Balanced Salt Solution (sham-injected) or Yersinia ruckeri (pathogen-injected). Eight hours following injection, fish were sacrificed for the assessment of general morphological (i.e., mass, length, condition factor, hepatic index) and immunological (i.e., leukocyte counts, spleen index) endpoints. To assess the molecular immune response to Y. ruckeri, kidney tissue was collected for transcriptomic analysis. A comparison of sham- and pathogen-injected fish revealed that >1800 genes and >500 gene networks were differentially expressed.Gene networks associated with inflammation, innate immunity, complement, hemorrhaging and iron absorption are highlighted and their utility within the context of immunotoxicity is discussed. These data reveal pathogen-related molecular endpoints to improve data interpretation of future studies utilizing the fathead minnow as a model for immunotoxicity.


Assuntos
Cyprinidae , Doenças dos Peixes/imunologia , Imunidade Inata , Transcriptoma/imunologia , Yersiniose/veterinária , Animais , Feminino , Doenças dos Peixes/microbiologia , Rim/imunologia , Rim/microbiologia , Modelos Animais , Yersiniose/imunologia , Yersiniose/microbiologia , Yersinia ruckeri/fisiologia
8.
Semin Respir Crit Care Med ; 41(5): 641-651, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32777849

RESUMO

Neurosarcoidosis (NS) is an often severe, destructive manifestation with a likely under-reported prevalence of 5 to 15% of sarcoidosis cases, and in its active phase demands timely treatment intervention. Clinical signs and symptoms of NS are variable and wide-ranging, depending on anatomical involvement. Cranial nerve dysfunction, cerebrospinal parenchymal disease, aseptic meningitis, and leptomeningeal disease are the most commonly recognized manifestations. However, non-organ-specific potentially neurologically driven symptoms, such as fatigue, cognitive dysfunction, and small fiber neuropathy, appear frequently.Heterogeneous clinical presentations and absence of any single conclusive test or biomarker render NS, and sarcoidosis itself, a challenging definitive diagnosis. Clinical suspicion of NS warrants a thorough systemic and neurologic evaluation hopefully resulting in supportive extraneural physical exam and/or tissue findings. Treatment targets the severity of the manifestation, with careful discernment of whether NS reflects active potentially reversible inflammatory granulomatous disease versus inactive postinflammatory damage whereby functional impairment is unlikely to be pharmacologically responsive. Non-organ-specific symptoms are poorly understood, challenging in deciphering reversibility and often identified too late to respond to conventional immunosuppressive/pharmacological treatment. Physical therapy, coping strategies, and stress reduction may benefit patients with all disease activity levels of NS.This publication provides an approach to screening, diagnosis, disease activity discernment, and pharmacological as well as nonpharmacological treatment interventions to reduce disability and protect health-related quality of life in NS.


Assuntos
Biomarcadores/análise , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Sarcoidose/diagnóstico , Sarcoidose/terapia , Doenças do Sistema Nervoso Central/sangue , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Diagnóstico Precoce , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Modalidades de Fisioterapia , Qualidade de Vida , Sarcoidose/sangue , Sarcoidose/líquido cefalorraquidiano
9.
Phys Rev Lett ; 122(12): 122501, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30978039

RESUMO

The structure of the extremely proton-rich nucleus _{8}^{11}O_{3}, the mirror of the two-neutron halo nucleus _{3}^{11}Li_{8}, has been studied experimentally for the first time. Following two-neutron knockout reactions with a ^{13}O beam, the ^{11}O decay products were detected after two-proton emission and used to construct an invariant-mass spectrum. A broad peak of width ∼3.4 MeV was observed. Within the Gamow coupled-channel approach, it was concluded that this peak is a multiplet with contributions from the four lowest ^{11}O resonant states: J^{π}=3/2_{1}^{-}, 3/2_{2}^{-}, 5/2_{1}^{+}, and 5/2_{2}^{+}. The widths and configurations of these states show strong, nonmonotonic dependencies on the depth of the p-^{9}C potential. This unusual behavior is due to the presence of a broad threshold resonant state in ^{10}N, which is an analog of the virtual state in ^{10}Li in the presence of the Coulomb potential. After optimizing the model to the data, only a moderate isospin asymmetry between ground states of ^{11}O and ^{11}Li was found.

10.
J Exp Biol ; 221(Pt 7)2018 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-29487156

RESUMO

The 'membrane pacemaker' hypothesis proposes a biochemical explanation for among-species variation in resting metabolism, based on the positive correlation between membrane docosahexaenoic acid (DHA) and metabolic rate. We tested this hypothesis using a novel model, altricial red-winged blackbird nestlings, predicting that the proportion of DHA in muscle and liver membranes should increase with the increasing metabolic rate of the nestling as it develops endothermy. We also used a dietary manipulation, supplementing the natural diet with fish oil (high DHA) or sunflower oil (high linoleic acid) to alter membrane composition and then assessed metabolic rate. In support of the membrane pacemaker hypothesis, DHA proportions increased in membranes from pectoralis muscle, muscle mitochondria and liver during post-hatch development. By contrast, elevated dietary DHA had no effect on resting metabolic rate, despite causing significant changes to membrane lipid composition. During cold challenges, higher metabolic rates were achieved by birds that had lower DHA and higher linoleic acid in membrane phospholipids. Given the mixed support for this hypothesis, we conclude that correlations between membrane DHA and metabolic rate are likely spurious, and should be attributed to a still-unidentified confounding variable.


Assuntos
Metabolismo Basal , Ácidos Docosa-Hexaenoicos/metabolismo , Lipídeos de Membrana/metabolismo , Fosfolipídeos/metabolismo , Aves Canoras/fisiologia , Ração Animal/análise , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/fisiologia , Temperatura Baixa , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Fígado/metabolismo , Mitocôndrias Musculares/metabolismo , Músculos Peitorais/metabolismo , Aves Canoras/crescimento & desenvolvimento
11.
J Exp Biol ; 221(Pt 14)2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29853545

RESUMO

Docosahexaenoic acid (DHA) is an important and abundant fatty acid moiety in vertebrate brains. We measured brain phospholipid composition during development in red-winged blackbirds (Agelaius phoeniceus), an altricial species that breeds in aquatic habitats. We also manipulated diet by feeding nestlings fish oil or sunflower oil. Finally, we assessed selective uptake of yolk by comparing the yolk fatty acid composition of freshly laid eggs and day-old hatchlings. Relative to other altricial species, blackbirds achieved high DHA in brain phospholipids (20% of phospholipid fatty acids in day-old hatchlings). This was not a result of selective uptake from the yolk, but rather a consequence of a high proportion of DHA in the yolk (2.5% of total lipids) at laying. Our dietary study confirmed that nestling brains are sensitive to fatty acid supply. Red-winged blackbirds may be able to advance cognitive development relative to other altricial species owing to their aquatic maternal diet.


Assuntos
Química Encefálica , Dieta/veterinária , Ácidos Docosa-Hexaenoicos/metabolismo , Gema de Ovo/química , Aves Canoras/metabolismo , Ração Animal/análise , Animais , Embrião não Mamífero/química , Desenvolvimento Embrionário , Óleos de Peixe/administração & dosagem , Óleos de Peixe/metabolismo , Distribuição Aleatória , Aves Canoras/embriologia , Óleo de Girassol/administração & dosagem , Óleo de Girassol/metabolismo
12.
Fish Shellfish Immunol ; 80: 80-87, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29859315

RESUMO

Exposures to polybrominated diphenyl ethers (PBDEs) have been shown to alter immune function in adult organisms across a variety of taxa. However, few if any studies have investigated the long-term consequences of early life stage PBDE exposures on immune function in fish. This study sought to determine the effects of early life stage BDE-47 exposure on pathogen resistance in the fathead minnow (Pimephales promelas) following an extended depuration period (≥180 d). Minnows were exposed to BDE-47 via a combination of maternal transfer and diet through 34 days post fertilization (dpf), raised to adulthood (>215 dpf) on a clean diet, then subjected to pathogen resistance trials. Early life stage exposures to BDE-47 did not affect the ability of females to survive from Yersinia ruckeri infection. However, the survival of BDE-47 exposed males was significantly reduced relative to controls, indicating that developmental exposures to BDE-47 altered male immunity. Because BDE-47 is a known thyroid hormone disruptor and thyroid hormone disruptors have the potential to adversely impact immune development and function, metrics indicative of thyroid disruption were evaluated, as were immune parameters known to be altered in response to thyroid disruption. BDE-47 exposed minnows exhibited signs of thyroid disruption (i.e., reduced growth); however, no alterations were observed in immune parameters known to be influenced by thyroid hormones (i.e., thymus size, expression of genes associated with lymphoid development) suggesting that the observed alterations in immunocompetence may occur through alternative mechanisms. Regardless of the mechanisms responsible, the results of this study demonstrate the potential for early life stage PBDE exposures to adversely impact immunity and illustrate that the immunological consequences of PBDE exposures are sex dependent.


Assuntos
Cyprinidae/imunologia , Resistência à Doença/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Animais , Cyprinidae/genética , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Larva , Masculino , Caracteres Sexuais , Timo , Glândula Tireoide , Yersiniose/imunologia , Yersiniose/veterinária , Yersinia ruckeri
13.
Environ Sci Technol ; 52(15): 8774-8784, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29943971

RESUMO

Mercury is a global contaminant, which may be microbially transformed into methylmercury (MeHg), which bioaccumulates. This results in potentially toxic body burdens in high trophic level organisms in aquatic ecosystems and maternal transfer to offspring. We previously demonstrated effects on developing fish including hyperactivity, altered time-to-hatch, reduced survival, and dysregulation of the dopaminergic system. A link between gut microbiota and central nervous system function in teleosts has been established with implications for behavior. We sequenced gut microbiomes of fathead minnows exposed to dietary MeHg to determine microbiome effects. Dietary exposures were repeated with adult CD-1 mice. Metabolomics was used to screen for metabolome changes in mouse brain and larval fish, and results indicate effects on lipid metabolism and neurotransmission, supported by microbiome data. Findings suggest environmentally relevant exposure scenarios may cause xenobiotic-mediated dysbiosis of the gut microbiome, contributing to neurotoxicity. Furthermore, small-bodied teleosts may be a useful model species for studying certain types of neurodegenerative diseases, in lieu of higher vertebrates.


Assuntos
Cyprinidae , Microbioma Gastrointestinal , Poluentes Químicos da Água , Animais , Ecossistema , Metaboloma , Camundongos
14.
Stroke ; 47(4): 918-22, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26965853

RESUMO

BACKGROUND AND PURPOSE: Although case reports have long identified a temporal association between cocaine use and ischemic stroke (IS), few epidemiological studies have examined the association of cocaine use with IS in young adults, by timing, route, and frequency of use. METHODS: A population-based case-control study design with 1090 cases and 1154 controls was used to investigate the relationship of cocaine use and young-onset IS. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between cocaine use and IS with and without adjustment for potential confounders. RESULTS: Ever use of cocaine was not associated with stroke with 28% of cases and 26% of controls reporting ever use. In contrast, acute cocaine use in the previous 24 hours was strongly associated with increased risk of stroke (age-sex-race adjusted odds ratio, 6.4; 95% confidence interval, 2.2-18.6). Among acute users, the smoking route had an adjusted odds ratio of 7.9 (95% confidence interval, 1.8-35.0), whereas the inhalation route had an adjusted odds ratio of 3.5 (95% confidence interval, 0.7-16.9). After additional adjustment for current alcohol, smoking use, and hypertension, the odds ratio for acute cocaine use by any route was 5.7 (95% confidence interval, 1.7-19.7). Of the 26 patients with cocaine use within 24 hours of their stroke, 14 reported use within 6 hours of their event. CONCLUSIONS: Our data are consistent with a causal association between acute cocaine use and risk of early-onset IS.


Assuntos
Isquemia Encefálica/etiologia , Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína/efeitos adversos , Acidente Vascular Cerebral/etiologia , Adolescente , Adulto , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
15.
Environ Sci Technol ; 50(14): 7834-41, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27326452

RESUMO

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a compound manufactured for use as a flame retardant, is a ubiquitous environmental contaminant and suspected endocrine disruptor. Though several studies have explored the reproductive effects of BDE-47 in adult fish, there is a paucity of data regarding the reproductive effects of early life stage exposure. The goal of this study was to assess the reproductive effects of early life stage BDE-47 exposure in fathead minnows (Pimephales promelas). To achieve this, minnows were exposed to either a low (57.68 µg BDE-47/g Artemia) or high (392.59 µg BDE-47/g Artemia) dose of BDE-47 from fertilization to 34 days postfertilization (dpf) via a combination of maternal transfer and dietary exposure. Larvae were then raised on a clean diet until sexual maturity (∼184 dpf) when reproductive function was evaluated using a 21 day breeding study. Fish exposed to BDE-47 had significantly reduced clutch size and fecundity relative to controls. BDE-47 exposed groups also had female-biased sex ratios and exposed males had fewer tubercles. Overall, this study demonstrates that exposure to BDE-47 during early life stages can alter both sexual differentiation and reproductive function.


Assuntos
Cyprinidae , Diferenciação Sexual , Animais , Disruptores Endócrinos/farmacologia , Retardadores de Chama , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/farmacologia
16.
Stroke ; 45(1): 281-3, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24193798

RESUMO

BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). METHODS: We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours. RESULTS: Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3). CONCLUSIONS: RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Comorbidade , Feminino , Fibrinolíticos/uso terapêutico , Glibureto/administração & dosagem , Glibureto/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Injeções Intravenosas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Projetos Piloto , Estudos Prospectivos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , População Branca , Adulto Jovem
17.
Stroke ; 45(4): 961-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24619398

RESUMO

BACKGROUND AND PURPOSE: Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case-control population and additionally performed a meta-analysis. METHODS: From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. RESULTS: Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9-6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2-28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4-5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1-1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1-2.0; P=0.005). CONCLUSIONS: The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.


Assuntos
Isquemia Encefálica/genética , Predisposição Genética para Doença/genética , Protrombina/genética , Acidente Vascular Cerebral/genética , Adolescente , Adulto , Idade de Início , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , População Branca/estatística & dados numéricos , Adulto Jovem
18.
J Surg Res ; 192(2): 480-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24980856

RESUMO

BACKGROUND: Near infrared fluorescence imaging using intravenous methylene blue (MB) is a novel technique that has potential to aid the parathyroid gland (PG) localization during thyroid and parathyroid surgery. The aim of this study was to examine MB fluorescence in the rabbit neck and determine the influence of MB dose and time following administration on fluorescence from thyroid and PGs. METHODS: Thyroid and external PGs were exposed in six New Zealand white rabbits under anesthesia. Varying doses of MB (0.025-3 mg/kg) were injected through the marginal ear vein. Near infrared fluorescence from exposed tissues was recorded at different time intervals (10-74 min) using Fluobeam 700. Specimens of identified glands were then resected for histologic assessment. RESULTS: Histology confirmed accurate identification of all excised thyroid and PGs; these were the only neck structures to demonstrate significant fluorescence. The parathyroid demonstrated lower fluorescence intensities and reduced washout times at all MB doses compared with the thyroid gland. A dose of 0.1 mg/kg MB was adequate to identify fluorescence; this also delineated the blood supply of the external PGs. CONCLUSIONS: The study demonstrates that near infrared fluorescence with intravenous MB helps differentiate between thyroid and PGs in the rabbit. This has potential to improve outcomes in thyroid and parathyroid surgery by increasing the accuracy of parathyroid identification; however, the findings require replication in human surgery. The use of low doses of MB may also avoid the side effects associated with currently used doses in humans (3-7 mg/kg).


Assuntos
Azul de Metileno , Glândulas Paratireoides/anatomia & histologia , Espectrometria de Fluorescência/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Glândula Tireoide/anatomia & histologia , Animais , Dissecação/métodos , Inibidores Enzimáticos/farmacocinética , Feminino , Injeções Intravenosas , Período Intraoperatório , Masculino , Azul de Metileno/farmacocinética , Pescoço/cirurgia , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/cirurgia , Coelhos , Glândula Tireoide/metabolismo , Glândula Tireoide/cirurgia
19.
Cerebrovasc Dis ; 37(3): 203-11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24557055

RESUMO

BACKGROUND AND PURPOSE: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). METHODS: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n=525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n=598) and post-SAMMPRIS (n=2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. RESULTS: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID=44%, post-WASID=85%, post-SAMMPRIS=94%) and posterior circulation (pre-WASID=36%, post-WASID=74%, post-SAMMPRIS=83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). CONCLUSIONS: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.


Assuntos
Angioplastia , Artérias Cerebrais/patologia , Fibrinolíticos/uso terapêutico , Arteriosclerose Intracraniana/terapia , Neurologia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Radiologia Intervencionista , Stents , Acidente Vascular Cerebral/prevenção & controle , Angioplastia/estatística & dados numéricos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel , Constrição Patológica , Quimioterapia Combinada , Uso de Medicamentos , Pesquisas sobre Atenção à Saúde , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento de Redução do Risco , Prevenção Secundária , Stents/estatística & dados numéricos , Acidente Vascular Cerebral/etiologia , Inquéritos e Questionários , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Estados Unidos , Varfarina/uso terapêutico
20.
J Vasc Interv Radiol ; 25(10): 1549-57, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24999164

RESUMO

PURPOSE: To study the relationship between intracranial thrombus length and number of stent retrievals, revascularization rates, and functional outcomes in stroke. MATERIALS AND METHODS: Retrospective data were collected from consecutive cases of stroke treated with endovascular procedures at a single institution from April 2012-September 2013. Thrombus length was measured in the anterior cerebral circulation. Demographic and clinical details; involved vessels; and procedural details, including the number of devices used and number of retrievals used for each device, were recorded. Revascularization rates and 90-day functional outcomes were recorded. RESULTS: Data regarding the length of thrombus in the anterior cerebral circulation were available for 28 patients. There was no significant association between thrombus length and number of stent retrievals (P = .3780), final thrombolysis in cerebral infarction (TICI) score (P = .4835), or 90-day modified Rankin Scale score (P = .4146). There was a significant difference (P = .0280) between number of retrievals and final TICI score, with lower number of retrieval passes corresponding to higher final TICI scores. CONCLUSIONS: The data suggest no relationship between thrombus length and number of stent retrievals, final TICI score, or functional neurologic outcomes at 90 days in stent retrieval thrombectomy for acute ischemic stroke. These results do not support a predictive value for thrombus length quantification in the evaluation of stroke.


Assuntos
Isquemia Encefálica/terapia , Remoção de Dispositivo , Procedimentos Endovasculares/instrumentação , Trombose Intracraniana/terapia , Stents , Acidente Vascular Cerebral/terapia , Trombectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Baltimore , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Trombose Intracraniana/fisiopatologia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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