Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
1.
A A Pract ; 18(6): e01793, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38836561

RESUMO

Serotonin syndrome (SS) is a life-threatening condition caused by serotonergic medications. We describe a unique case of SS likely caused by prolonged exposure to propofol and remifentanil alone. A young male presented for vestibular schwannoma resection. Several hours into the case, the patient demonstrated hyperthermia and hemodynamic instability, followed by clonus, rigidity, shivering, and tachycardia after emergence. SS was diagnosed using Hunter's criteria and improved with supportive measures. While the patient endorsed a history of methamphetamine use, his urine drug screen was negative. The possibility of SS should be considered when administering propofol and remifentanil, particularly with prolonged infusions.


Assuntos
Craniotomia , Propofol , Remifentanil , Síndrome da Serotonina , Humanos , Remifentanil/efeitos adversos , Remifentanil/administração & dosagem , Masculino , Propofol/efeitos adversos , Propofol/administração & dosagem , Síndrome da Serotonina/induzido quimicamente , Craniotomia/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Adulto , Infusões Intravenosas , Neuroma Acústico/cirurgia , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem
2.
PLoS One ; 18(7): e0288988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37478144

RESUMO

OBJECTIVE: To compare efficacy of oral versus intravenous (IV) methadone on postoperative pain and opioid requirements after spine surgery. METHODS: This was a retrospective, single-academic center cohort study evaluating 1010 patients who underwent >3 level spine surgery from January 2017 to May 2020 and received a one-time dose of oral or intravenous methadone prior to surgery. The primary outcome measured was postoperative opioid use in oral morphine equivalents (ME) and verbal response scale (VRS) pain scores up to postoperative day (POD) three. Secondary outcomes were time to first bowel movement and adverse effects (reintubation, myocardial infarction, and QTc prolongation) up to POD 3. RESULTS: A total of 687 patients received oral and 317 received IV methadone, six patients were excluded. The IV group received a significantly greater methadone morphine equivalent (ME) dose preoperatively (112.4 ± 83.0 mg ME versus 59.3 ± 60.9 mg ME, p < 0.001) and greater total (methadone and non-methadone) opioid dose (119.1 ± 81.4 mg ME versus 63.9 ± 62.5 mg ME, p < 0.001), intraoperatively. Although pain scores for the oral group were non-inferior to the IV group for all postoperative days (POD), non-inferiority for postoperative opioid requirements was demonstrated only on POD 3. Based on the joint hypothesis for the co-primary outcomes, oral methadone was non-inferior to IV methadone on POD 3 only. No differences in secondary outcomes, including QTc prolongation and arrhythmias, were noted between the groups. CONCLUSIONS: Oral methadone is a feasible alternative to IV methadone for patients undergoing spine surgery regarding both pain scores and postoperative opioid consumption.


Assuntos
Síndrome do QT Longo , Transtornos Relacionados ao Uso de Opioides , Humanos , Adulto , Metadona/uso terapêutico , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Morfina , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome do QT Longo/tratamento farmacológico
3.
Cell ; 185(24): 4488-4506.e20, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36318922

RESUMO

When challenged by hypertonicity, dehydrated cells must recover their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless condensates, initiating a phosphorylation-dependent signal that drives net ion influx via the SLC12 cotransporters to restore cell volume. WNK1 condensate formation is driven by its intrinsically disordered C terminus, whose evolutionarily conserved signatures are necessary for efficient phase separation and volume recovery. This disorder-encoded phase behavior occurs within physiological constraints and is activated in vivo by molecular crowding rather than changes in cell size. This allows kinase activity despite an inhibitory ionic milieu and permits cell volume recovery through condensate-mediated signal amplification. Thus, WNK kinases are physiological crowding sensors that phase separate to coordinate a cell volume rescue response.


Assuntos
Proteínas Serina-Treonina Quinases , Fosforilação , Tamanho Celular
4.
Biochemistry ; 58(14): 1892-1904, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30855939

RESUMO

The biosynthesis of Fe-S clusters and other thio-cofactors requires the participation of redox agents. A shared feature in these pathways is the formation of transient protein persulfides, which are susceptible to reduction by artificial reducing agents commonly used in reactions in vitro. These agents modulate the reactivity and catalytic efficiency of biosynthetic reactions and, in some cases, skew the enzymes' kinetic behavior, bypassing sulfur acceptors known to be critical for the functionality of these pathways in vivo. Here, we provide kinetic evidence for the selective reactivity of the Bacillus subtilis Trx (thioredoxin) system toward protein-bound persulfide intermediates. Our results demonstrate that the redox flux of the Trx system modulates the rate of sulfide production in cysteine desulfurase assays. Likewise, the activity of the Trx system is dependent on the rate of persulfide formation, suggesting the occurrence of coupled reaction schemes between both enzymatic systems in vitro. Inactivation of TrxA (thioredoxin) or TrxR (thioredoxin reductase) impairs the activity of Fe-S enzymes in B. subtilis, indicating the involvement of the Trx system in Fe-S cluster metabolism. Surprisingly, biochemical characterization of TrxA reveals that this enzyme is able to coordinate Fe-S species, resulting in the loss of its reductase activity. The inactivation of TrxA through the coordination of a labile cluster, combined with its proposed role as a physiological reducing agent in sulfur transfer pathways, suggests a model for redox regulation. These findings provide a potential link between redox regulation and Fe-S metabolism.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Sulfetos/metabolismo , Enxofre/metabolismo , Tiorredoxinas/metabolismo , Bacillus subtilis/enzimologia , Liases de Carbono-Enxofre/metabolismo , Cisteína/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Cinética , Oxirredução , Ligação Proteica , Tiorredoxina Dissulfeto Redutase/metabolismo
6.
J Neurosci ; 35(15): 6165-78, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25878288

RESUMO

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.


Assuntos
Encéfalo/metabolismo , Proteínas F-Box/metabolismo , Regulação da Expressão Gênica/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Encéfalo/citologia , Células Cultivadas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Proteínas F-Box/genética , Células HEK293 , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Transporte Proteico/genética , Sinapses/efeitos dos fármacos , Sinapses/ultraestrutura , Sinaptossomos/metabolismo , Sinaptossomos/ultraestrutura , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo
7.
J Biol Chem ; 289(10): 7038-7048, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24469452

RESUMO

The amyloid precursor protein (APP) is an integral membrane glycoprotein whose cleavage products, particularly amyloid-ß, accumulate in Alzheimer disease (AD). APP is present at synapses and is thought to play a role in both the formation and plasticity of these critical neuronal structures. Despite the central role suggested for APP in AD pathogenesis, the mechanisms regulating APP in neurons and its processing into cleavage products remain incompletely understood. F-box only protein 2 (Fbxo2), a neuron-enriched ubiquitin ligase substrate adaptor that preferentially binds high-mannose glycans on glycoproteins, was previously implicated in APP processing by facilitating the degradation of the APP-cleaving ß-secretase, ß-site APP-cleaving enzyme. Here, we sought to determine whether Fbxo2 plays a similar role for other glycoproteins in the amyloid processing pathway. We present in vitro and in vivo evidence that APP is itself a substrate for Fbxo2. APP levels were decreased in the presence of Fbxo2 in non-neuronal cells, and increased in both cultured hippocampal neurons and brain tissue from Fbxo2 knock-out mice. The processing of APP into its cleavage products was also increased in hippocampi and cultured hippocampal neurons lacking Fbxo2. In hippocampal slices, this increase in cleavage products was accompanied by a significant reduction in APP at the cell surface. Taken together, these results suggest that Fbxo2 regulates APP levels and processing in the brain and may play a role in modulating AD pathogenesis.


Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas F-Box/metabolismo , Animais , Células Cultivadas , Proteínas F-Box/genética , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Neurônios/metabolismo
8.
Vasc Endovascular Surg ; 47(7): 566-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23922156

RESUMO

Spontaneous compartment syndrome is a rare condition and requires urgent surgical treatment to achieve favorable outcome. Several cases have been reported in the literature, and it has been associated with patients with diabetes. We present a case of acute spontaneous sequential compartment syndrome of the lower limbs in a patient with poorly controlled type 1 diabetes.


Assuntos
Síndromes Compartimentais/etiologia , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Extremidade Inferior/irrigação sanguínea , Adulto , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/cirurgia , Descompressão Cirúrgica , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/cirurgia , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Fatores de Risco , Resultado do Tratamento
9.
BMJ Case Rep ; 20122012 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-22605700

RESUMO

Metastasis of primary endometrial adenocarcinoma to unusual sites has been occasionally reported. However, the authors believe this to be the first case report of metastasis to the appendix. This occurred more than 10 years after curative resection, and presented as sepsis with an intra-abdominal focus.


Assuntos
Adenocarcinoma/secundário , Neoplasias do Apêndice/secundário , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Adenocarcinoma/terapia , Apendicectomia , Neoplasias do Apêndice/terapia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Cuidados Paliativos
10.
Vasc Endovascular Surg ; 46(1): 62-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22156160

RESUMO

INTRODUCTION: We report 2 cases where the Outback catheter facilitated extra-anatomical bypass after vessel perforation during attempted subintimal vessel dissection. REPORT: Attempted subintimal angioplasty of the superficial femoral artery (SFA) resulted in vessel perforation in 2 patients with chronic SFA occlusion and limb ischemia. Due to the lack of other endovascular or surgical options, the Outback catheter was used to reenter the patent lumen distal to the perforation. A stent graft was then deployed from proximal to the perforation to beyond the reentry point with successful outcomes. DISCUSSION: Although the reentry devices are typically used to enter the lumen from the subintimal plane, this novel technique involves using the Outback catheter to enter from the extravascular compartment and facilitate bypass of the SFA occlusion via an extra-anatomical route. This novel technique can be used to restore in-line blood flow when attempted endovascular revascularization failed due to vessel perforation.


Assuntos
Angioplastia/instrumentação , Arteriopatias Oclusivas/terapia , Catéteres , Artéria Femoral , Isquemia/terapia , Lesões do Sistema Vascular/terapia , Idoso , Angioplastia/efeitos adversos , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico por imagem , Constrição Patológica , Desenho de Equipamento , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/lesões , Humanos , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Radiografia , Terapia de Salvação , Stents , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia
11.
Vasc Endovascular Surg ; 45(5): 442-6, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21571773

RESUMO

PURPOSE: To review the outcomes of patients undergoing emergency endovascular repair of aortocaval fistula (ACF) secondary to abdominal aortic aneurysm (AAA). CASE REPORT: Four consecutive patients who underwent emergency endovascular repair of ACF associated with AAA in a tertiary institution between 2002 and 2009. Of the 4 patients, 3 had initially been misdiagnosed and managed for several days by other specialists for their symptoms prior to diagnosis of their ACF. Three patients died in the early postoperative period. The fourth patient made a satisfactory postoperative recovery but subsequently required further endovascular surgery to treat a persistent type 1 endoleak. CONCLUSIONS: Our experience illustrates the importance of early diagnosis and management of ACF. Even in experienced hands, the management of spontaneous ACF associated with AAA is challenging. Endovascular surgery may still have a role in improving outcomes in these patients.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Doenças da Aorta/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Fístula Vascular/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Aneurisma da Aorta Abdominal/diagnóstico , Doenças da Aorta/diagnóstico , Doenças da Aorta/etiologia , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Emergências , Endoleak/etiologia , Endoleak/cirurgia , Procedimentos Endovasculares/efeitos adversos , Evolução Fatal , Humanos , Angiografia por Ressonância Magnética , Masculino , Flebografia/métodos , Reoperação , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fístula Vascular/diagnóstico , Fístula Vascular/etiologia , Veia Cava Inferior/patologia
12.
Circulation ; 107(24): 3047-52, 2003 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-12796133

RESUMO

BACKGROUND: Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens. METHODS AND RESULTS: Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (kappa=0.75) and intraobserver (kappa=0.9) agreement for reading MRDTI scans was good. CONCLUSIONS: MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease.


Assuntos
Isquemia Encefálica , Trombose das Artérias Carótidas/diagnóstico , Estenose das Carótidas/diagnóstico , Imageamento por Ressonância Magnética , Idoso , Isquemia Encefálica/etiologia , Trombose das Artérias Carótidas/complicações , Trombose das Artérias Carótidas/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Endarterectomia , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade
13.
Circulation ; 107(24): 3053-8, 2003 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-12796136

RESUMO

BACKGROUND: It is recognized that complicated plaque largely accounts for the morbidity and mortality from atherosclerosis. Ideally, investigation of symptomatic and asymptomatic patients would identify atheromatous plaques independently of stenosis. We have previously shown that a magnetic resonance direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as high signal within the carotid arterial wall. We used this technique to examine the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries of recently symptomatic patients with suspected carotid artery stenosis and to compare this with their contralateral arteries and with those of healthy age- and sex-matched controls. METHODS AND RESULTS: The carotid arteries of 120 patients with suspected severe carotid artery stenosis and previous acute cerebral ischemia were imaged using MRDTI, as were 28 control arteries. High signal was not seen in any control artery. However, there was a 60% prevalence of high signal, suggestive of complicated plaque in the patients' ipsilateral arteries. The prevalence of high signal was significantly greater in the patients' ipsilateral vessels compared with the contralateral, asymptomatic side (60% versus 36%, chi2 P<0.001), particularly for vessels of only moderate stenosis. CONCLUSIONS: MRDTI high signal suggestive of complicated plaque is prevalent in the ipsilateral carotid arteries of patients with carotid stenosis and recent cerebral ischemic events. MRDTI has a potential role in identifying "at risk" plaque, studying atherogenesis and the effects of plaque-modifying strategies.


Assuntos
Isquemia Encefálica/diagnóstico , Doenças das Artérias Carótidas/diagnóstico , Trombose das Artérias Carótidas/diagnóstico , Estenose das Carótidas/diagnóstico , Imageamento por Ressonância Magnética , Isquemia Encefálica/epidemiologia , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/epidemiologia , Trombose das Artérias Carótidas/epidemiologia , Estenose das Carótidas/epidemiologia , Comorbidade , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Masculino , Prevalência , Valores de Referência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...