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1.
Am J Emerg Med ; 77: 1-6, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38096634

RESUMO

BACKGROUND: Many patients who are admitted to the intensive care unit (ICU) have needs which rapidly resolve and are discharged alive within 24 h. We sought to characterize the outcomes of critically ill trauma victims at our institution with a short stay in the ICU. METHODS: We conducted a retrospective cohort study of all critically ill adult trauma victims presenting to our ED between January 1st, 2011 and December 31st, 2019. We included patients who were endotracheally intubated in either the prehospital setting or the ED and were admitted either to the operating room (OR), angiography suite, or ICU. Our primary outcome was the proportion of patients who were discharged alive from the ICU within 24 h. RESULTS: We included 3869 patients meeting the criteria above who were alive at 24 h. This population was 78% male with a median age of 40 and 76% of patients suffered from blunt trauma. The median injury severity score (ISS) of the group was 21 [inter-quartile range (IQR) 11-30]. In-hospital mortality amongst the group was 12%. 17% of the group were discharged alive from the ICU within 24 h. Thirty-four percent of the group had an ISS ≤ 15. Of the group which left the ICU alive within 24 h, six patients (0.9%) died in the hospital, 2 % of patients were re-admitted to an ICU, and 0.6% of patients required re-intubation. CONCLUSIONS: We found that 17% of patients who were intubated in the prehospital setting or emergency department and subsequently hospitalized were discharged alive from the ICU within 24 h.


Assuntos
Estado Terminal , Respiração Artificial , Adulto , Humanos , Masculino , Feminino , Estudos Retrospectivos , Cuidados Críticos , Serviço Hospitalar de Emergência , Unidades de Terapia Intensiva , Tempo de Internação
2.
J Intensive Care Med ; 38(11): 1051-1059, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37287235

RESUMO

PURPOSE: The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. METHODS: Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. RESULTS: Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance (P = .09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. CONCLUSIONS: We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating.


Assuntos
Hipotensão , Sepse , Choque Séptico , Adulto , Humanos , Choque Séptico/terapia , Estudos Retrospectivos , Sepse/terapia , Ressuscitação , Hidratação , Ácido Láctico
3.
Cardiol Young ; 33(10): 1896-1901, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36330834

RESUMO

INTRODUCTION: Patients with Fontan physiology require non-cardiac surgery. Our objectives were to characterise perioperative outcomes of patients with Fontan physiology undergoing non-cardiac surgery and to identify characteristics which predict discharge on the same day. MATERIALS AND METHOD: Children and young adults with Fontan physiology who underwent a non-cardiac surgery or an imaging study under anaesthesia between 2013 and 2019 at a single-centre academic children's hospital were reviewed in a retrospective observational study. Continuous variables were compared using the Wilcoxon rank sum test, and categorical variables were analysed using the Chi-square test or Fisher's exact test. Multivariable logistic regression analysis results are presented by adjusted odds ratios with 95% confidence intervals and p values. RESULTS: 182 patients underwent 344 non-cardiac procedures with anaesthesia. The median age was 11 years (IQR 5.2-18), 56.4% were male. General anaesthesia was administered in 289 (84%). 125 patients (36.3%) were discharged on the same day. On multivariable analysis, independent predictors that reduced the odds of same-day discharge included the chronic condition index (OR 0.91 per additional chronic condition, 95% CI 0.76-0.98, p = 0.022), undergoing a major surgical procedure (OR 0.17, 95% CI 0.05-0.64, p = 0.009), the use of intraoperative inotropes (OR 0.48, 95% CI 0.25-0.94, p = 0.031), and preoperative admission (OR = 0.24, 95% CI: 0.1-0.57, p = 0.001). DISCUSSION: In a contemporary cohort of paediatric and young adults with Fontan physiology, 36.3% were able to be discharged on the same day of their non-cardiac procedure. Well selected patients with Fontan physiology can undergo anaesthesia without complications and be discharged same day.


Assuntos
Técnica de Fontan , Complicações Pós-Operatórias , Humanos , Masculino , Criança , Adulto Jovem , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hospitalização , Anestesia Geral , Estudos Retrospectivos , Doença Crônica , Técnica de Fontan/efeitos adversos
4.
J Emerg Med ; 64(5): 574-583, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37045721

RESUMO

BACKGROUND: Patients admitted to an intensive care unit (ICU) requiring invasive mechanical ventilation who are discharged alive from the ICU within 24 h are poorly characterized in the literature. OBJECTIVE: Our aim was to characterize a cohort of intubated emergency department (ED) patients who are extubated and discharged from the ICU within 24 h. METHODS: We conducted a retrospective, observational cohort study at a single level I trauma center from January 2017 to December 2019. We included adults who were admitted to an ICU from the ED requiring invasive mechanical ventilation. Our primary outcome was the proportion of patients who were discharged from the ICU alive within 24 h. RESULTS: Of 13,374 ED patients admitted to an ICU during the study period, 2871 patients were intubated and ventilated in the prehospital or ED settings. Of these, 14% were discharged alive from the ICU within 24 h of admission. Only 21% of these patients were intubated in the ED. We identified the following two distinct subpopulations comprising 62% of this short-stay group: patients with a primary discharge diagnosis of intoxication (47%) and minimally injured trauma patients (53%), with 4% of patients in both subgroups. CONCLUSIONS: A total of 14% of patients receiving intubation with mechanical ventilation in the prehospital environment or in the ED were discharged alive from the ICU within 24 h. We identified two distinct subgroups of patients with a short stay in intensive care who may be candidates for ED extubation, including patients with intoxication and minimally injured trauma patients.


Assuntos
Cuidados Críticos , Respiração Artificial , Adulto , Humanos , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Tempo de Internação , Serviço Hospitalar de Emergência , Unidades de Terapia Intensiva
5.
Paediatr Anaesth ; 32(2): 302-311, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34877742

RESUMO

Bronchoscopy-guided diagnostic and interventional airway procedures are gaining in popularity and prominence in pediatric surgery. Many of these procedures have been used successfully in the adult population but have not been used in children due to a lack of appropriately sized instruments. Recent technological advances have led to the creation of instruments to enable many more diagnostic and therapeutic procedures to be done under bronchoscopic guidance. These procedures vary significantly in their length and invasiveness and require vastly different anesthetic plans that must be easily adapted to situational and procedural changes. In addition to close communication between the anesthesiology and procedural teams; an understanding of the type of procedure, anesthetic requirements, and potential patient risks is paramount to a successful anesthetic. This review will focus on new rigid bronchoscopic procedures, goals for their respective anesthetic management, and unique tips and trick for how to maintain adequate oxygenation and ventilation in each scenario.


Assuntos
Anestesia , Anestesiologia , Anestesia/métodos , Broncoscopia/métodos , Criança , Humanos , Sistema Respiratório
6.
Int J Hyperthermia ; 36(1): 493-498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30935256

RESUMO

BACKGROUND: Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been used to treat various peritoneal malignancies. Cisplatin and mitomycin C (MMC) are agents commonly used in these procedures and, individually, each has been associated with acute kidney injury (AKI). There is limited literature on the complications associated with the use of both agents in HIPEC. Therefore, we sought to determine the incidence of nephrotoxicity and electrolyte abnormalities in patients undergoing laparoscopic HIPEC using this chemotherapeutic combination. METHODS: We retrospectively evaluated patients undergoing laparoscopic HIPEC for gastric or gastroesophageal adenocarcinoma using both cisplatin and MMC. Sodium thiosulfate was given for renal protection and kidney function was evaluated daily up to postoperative day #2. Details regarding patient characteristics, selection criteria, chemotherapeutic regimen, perioperative lab values and anesthetic management were collected. RESULTS: Twenty-three patients underwent 31 laparoscopic HIPEC procedures. Fifteen (65%) were male and the median age was 57 (range 21-75). Thirteen procedures were associated with an elevation in creatinine (Cr) with the median difference between POD#2 and baseline being 0.09 mg/dL (range 0-0.43). The glomerular filtration rate median difference between POD#2 and baseline was -17 mL/min/1.37 sq. m (range -42 to 11). No cases demonstrated AKI, defined as a 50% increase in Cr levels above baseline. An 84% incidence of postoperative hypophosphatemia (26/31) and 94% incidence of postoperative hypocalcemia (29/31) was observed. CONCLUSION: The laparoscopic approach to HIPEC using both cisplatin and MMC in our cohort was not associated with an increased incidence of AKI. The incidence of hypophosphatemia and hypocalcemia needs further evaluation to determine the exact etiology. Precis' statement: We retrospectively studied the association of AKI with the combined use of cisplatin and MMC in laparoscopic HIPEC.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Cisplatino/efeitos adversos , Terapia Combinada/efeitos adversos , Hipertermia Induzida/métodos , Laparoscopia/métodos , Mitomicina/efeitos adversos , Adulto , Idoso , Cisplatino/farmacologia , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Estudos Retrospectivos , Adulto Jovem
7.
Anesth Analg ; 127(3): 724-729, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29734243

RESUMO

BACKGROUND: While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. METHODS: We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. RESULTS: The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal, general surgery, and maxillofacial procedures. CONCLUSIONS: Intraoperative cardiovascular events and respiratory events in patients with CHD were relatively common. While cardiovascular events were highly associated with cardiovascular status, respiratory events were not associated with cardiovascular status.


Assuntos
Doenças Cardiovasculares/epidemiologia , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Transtornos Respiratórios/epidemiologia , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais/tendências , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Incidência , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico , Transtornos Respiratórios/diagnóstico , Fatores de Risco
8.
J Neuroinflammation ; 14(1): 48, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28264694

RESUMO

BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1+ neurons in both wild type mice and a mouse model of Alzheimer's disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis. RESULTS: While C1q expression in the brain was unaffected after inactivation of C1qa in Thy-1+ neurons, the brains of C1qa FL/FL :Cx3cr1 CreERT2 mice in which C1qa was ablated in microglia were devoid of C1q with the exception of limited C1q in subsets of interneurons. Surprisingly, this loss of C1q occurred even in the absence of tamoxifen by 1 month of age, demonstrating that Cre activity is tamoxifen-independent in microglia in Cx3cr1 CreERT2/WganJ mice. C1q expression in C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice continued to decline and remained almost completely absent through aging and in AD model mice. No difference in C1q was detected in the liver or kidney from C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice relative to controls, and C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice had minimal, if any, reduction in plasma C1q. CONCLUSIONS: Thus, microglia, but not neurons or peripheral sources, are the dominant source of C1q in the brain. While demonstrating that the Cx3cr1 CreERT2/WganJ deleter cannot be used for adult-induced deletion of genes in microglia, the model described here enables further investigation of physiological roles of C1q in the brain and identification of therapeutic targets for the selective control of complement-mediated activities contributing to neurodegenerative disorders.


Assuntos
Encéfalo/citologia , Complemento C1q/deficiência , Microglia/metabolismo , Animais , Animais Recém-Nascidos , Antígeno CD11b/genética , Antígeno CD11b/metabolismo , Receptor 1 de Quimiocina CX3C , Complemento C1q/genética , Regulação da Expressão Gênica/fisiologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Neurópilo/metabolismo , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Antígenos Thy-1/genética , Antígenos Thy-1/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
9.
Ann Clin Psychiatry ; 29(4): 242-248, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29069109

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a relatively new treatment modality for patients with major depressive disorder (MDD). Numerous studies have demonstrated the efficacy of TMS for MDD in the general population. However, there is limited information regarding clinical outcomes among veterans receiving TMS for MDD. METHODS: The clinical outcome and characteristics of all veterans with MDD who were treated with TMS as outpatients at the James A. Haley Veterans' Hospital from October 2013 to December 2016 were assessed. RESULTS: Among 40 patients who received TMS, there was a significant improvement of depressive symptoms using the Quick Inventory of Depressive Symptomatology-Self-Report (45% response, 20% remission) and the Montgomery-Åsberg Depression Rating Scale (61.9% response, 42.9% remission). In addition to significant improvement in depressive symptoms, self-report of anxiety symptoms and function significantly improved. TMS was generally well tolerated, with only a small percentage of patients discontinuing treatment due to side effects. No seizures or persistent adverse effects were observed or reported. CONCLUSIONS: TMS is an effective and well-tolerated option for MDD in a veteran population with significant treatment resistance and multiple comorbidities.


Assuntos
Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana/métodos , Veteranos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Autorrelato , Resultado do Tratamento
10.
J Neurosci ; 35(27): 9977-89, 2015 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-26156998

RESUMO

With severe injury or disease, microglia become chronically activated and damage the local brain environment, likely contributing to cognitive decline. We previously discovered that microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in the healthy adult brain, and we have exploited this dependence to determine whether such activated microglia contribute deleteriously to functional recovery following a neuronal lesion. Here, we induced a hippocampal lesion in mice for 25 d via neuronal expression of diphtheria toxin A-chain, producing both a neuroinflammatory reaction and behavioral alterations. Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. This post-lesion treatment paradigm improved functional recovery on elevated plus maze and Morris water maze, concomitant with reductions in elevated proinflammatory molecules, as well as normalization of lesion-induced alterations in synaptophysin and PSD-95. Further exploration of the effects of microglia on synapses in a second cohort of mice revealed that dendritic spine densities are increased with long-term microglial elimination, providing evidence that microglia shape the synaptic landscape in the adult mouse brain. Furthermore, in these same animals, we determined that microglia play a protective role during lesioning, whereby neuronal loss was potentiated in the absence of these cells. Collectively, we demonstrate that microglia exert beneficial effects during a diphtheria toxin-induced neuronal lesion, but impede recovery following insult. SIGNIFICANCE STATEMENT: It remains unknown to what degree, and by what mechanisms, chronically activated microglia contribute to cognitive deficits associated with brain insults. We induced a genetic neuronal lesion in mice for 25 d and found activated microglia to increase inflammation, alter synaptic surrogates, and impede behavioral recovery. These lesion-associated deficits were ameliorated with subsequent microglial elimination, underscoring the importance of developing therapeutics aimed at eliminating/modulating chronic microglial activation. Additionally, we found long-term microglial depletion globally increases dendritic spines by ∼35% in the adult brain, indicating that microglia continue to sculpt the synaptic landscape in the postdevelopmental brain under homeostatic conditions. Microglial manipulation can therefore be used to investigate the utility of increasing dendritic spine numbers in postnatal conditions displaying synaptic aberrations.


Assuntos
Hipocampo/patologia , Microglia/fisiologia , Neurônios/patologia , Recuperação de Função Fisiológica/fisiologia , Aminopiridinas/farmacologia , Animais , Sintomas Comportamentais/etiologia , Barreira Hematoencefálica/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Transtornos Cognitivos/etiologia , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Doxiciclina/farmacologia , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Fosfopiruvato Hidratase/metabolismo , Pirróis/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Sinaptofisina/metabolismo
12.
J Biol Chem ; 288(1): 654-65, 2013 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-23150673

RESUMO

Complement protein C1q is induced in the brain in response to a variety of neuronal injuries, including Alzheimer disease (AD), and blocks fibrillar amyloid-ß (fAß) neurotoxicity in vitro. Here, we show that C1q protects immature and mature primary neurons against fAß toxicity, and we report for the first time that C1q prevents toxicity induced by oligomeric forms of amyloid-ß (Aß). Gene expression analysis reveals C1q-activated phosphorylated cAMP-response element-binding protein and AP-1, two transcription factors associated with neuronal survival and neurite outgrowth, and increased LRP1B and G protein-coupled receptor 6(GPR6) expression in fAß-injured neurons. Silencing of cAMP-response element-binding protein, LRP1B or GPR6 expression inhibited C1q-mediated neuroprotection from fAß-induced injury. In addition, C1q altered the association of oligomeric Aß and fAß with neurons. In vivo, increased hippocampal expression of C1q, LRP1B, and GPR6 is observed as early as 2 months of age in the 3 × Tg mouse model of AD, whereas no such induction of LRP1B and GPR6 was seen in C1q-deficient AD mice. In contrast, expression of C1r and C1s, proteases required to activate the classical complement pathway, and C3 showed a significant age-dependent increase only after 10-13 months of age when Aß plaques start to accumulate in this AD model. Thus, our results identify pathways by which C1q, up-regulated in vivo early in response to injury without the coordinate induction of other complement components, can induce a program of gene expression that promotes neuroprotection and thus may provide protection against Aß in preclinical stages of AD and other neurodegenerative processes.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Complemento C1q/metabolismo , Regulação da Expressão Gênica , Receptores Acoplados a Proteínas G/fisiologia , Receptores de LDL/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Modelos Biológicos , Doenças Neurodegenerativas/metabolismo , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Receptores de LDL/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima
14.
Biochim Biophys Acta ; 1824(10): 1069-79, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22709576

RESUMO

Aggregation of beta-amyloid (Aß) into oligomers and fibrils is associated with the pathology of Alzheimer's disease. The major structural characteristics of Aß fibrils include the presence of ß sheet-loop-ß sheet conformations. Several lines of study suggested a potentially important role of the Aß loop forming sequence (referred to as the Aß linker region) in Aß aggregation. Effects of mutations in several charged residues within the Aß linker region on aggregation have been extensively studied. However, little is known about oligomerization effects of sequence variation in other residues within the Aß linker region. Moreover, modulation effects of the Aß linker mutants on Aß aggregation have yet to be characterized. Here, we created and characterized Aß linker variants containing sequences preferentially found in specific ß turn conformations. Our results indicate that a propensity to form oligomers may be changed by local sequence variation in the Aß linker region without mutating the charged residues. Strikingly, one Aß linker variant rapidly formed protofibrillar oligomers, which did not convert to fibrillar aggregates in contrast to Aß aggregating to fibrils under similar incubation conditions. Moreover, our results suggest that molecular forces critical in oligomerization and fibrillization may differ at least for those involved in the linker region. When co-incubated with Aß, some Aß linker variants were found to induce accumulation of Aß oligomers. Our results suggest that engineering of the Aß linker region as described in this paper may represent a novel approach to control Aß oligomerization and create Aß oligomerization modulators.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Sequência de Aminoácidos , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/genética , Cromatografia em Gel , Dicroísmo Circular , Humanos , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Mutação , Homologia de Sequência de Aminoácidos
15.
Emerg Infect Dis ; 19(8): 1276-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23876744

RESUMO

US vibriosis rates have increased since 1996, and many Vibrio vulnificus infections are fatal. In April 2003, California implemented a regulation restricting the sale of raw oysters harvested from the Gulf of Mexico during April 1-October 31, unless they were processed to reduce V. vulnificus to nondetectable levels. We analyzed California cases of V. vulnificus infection before and after the regulation's implementation and compared case data with data from other states. The annual number of reported V. vulnificus infections and deaths in California with patient's sole exposure to raw oysters dropped from 0 to 6 cases and 0 to 5 deaths per year during 1991-2002, before implementation, to 0 during 2003-2010, after implementation (p = 0.0005 for both). In other states, median annual numbers of similar cases and deaths increased slightly after 2002. The data strongly suggest that the 2003 regulation led to a significant reduction in reported raw oyster-associated V. vulnificus illnesses and deaths.


Assuntos
Manipulação de Alimentos/legislação & jurisprudência , Doenças Transmitidas por Alimentos/prevenção & controle , Ostreidae/microbiologia , Frutos do Mar/microbiologia , Vibrioses/prevenção & controle , Vibrio vulnificus , Adulto , Idoso , Animais , California/epidemiologia , Monitoramento Epidemiológico , Microbiologia de Alimentos/legislação & jurisprudência , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/mortalidade , Humanos , Pessoa de Meia-Idade , Vibrioses/mortalidade
16.
Cureus ; 15(1): e33393, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36751225

RESUMO

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

17.
J Int Neuropsychol Soc ; 18(5): 927-30, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22643119

RESUMO

Although frontal patients show impaired decision-making on the Iowa Gambling Task (IGT), there has been no follow-up study to date to determine whether there is recovery of function over time. We examined neurological participants' performance on repeated administrations of the IGT over the course of 6 years. We found that, while non-neurological participants showed considerable improvement due to practice effects on the IGT, patients with ventromedial prefrontal cortex (VMPFC) damage persisted in showing impaired performance on each retest. These results validate the clinical observations that VMPFC dysfunction does not appear to be subject to autonomous recovery over time in real-life. (JINS, 2012, 18, 1-4).


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Transtornos Cognitivos/etiologia , Tomada de Decisões/fisiologia , Deficiências da Aprendizagem/etiologia , Córtex Pré-Frontal/patologia , Adulto , Idoso , Análise de Variância , Transtornos Cognitivos/diagnóstico , Feminino , Jogos Experimentais , Humanos , Deficiências da Aprendizagem/diagnóstico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
18.
Anesth Analg ; 114(2): 349-68, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22178627

RESUMO

The development of the laryngeal mask airway in 1981 was an important first step toward widespread use and acceptance of the extraglottic airway (EGA). The term extraglottic is used in this review to encompass those airways that do not violate the larynx, in addition to those with a supraglottic position. Although the term extraglottic may be broad and include airways such as tracheostomy tubes, the term supraglottic does not describe a large number of devices with subglottic components and is too narrow for a discussion of modern devices. EGAs have flourished in practice, and now a wide variety of devices are available for an ever-expanding array of applications. In this review we attempt to clarify the current state of EGA devices new and old, and to illustrate their use in numerous settings. Particular attention is paid to the use of EGAs in special situations such as obstetric, pediatric, prehospital, and nontraditional "out of the operating room" settings. The role of the EGA in difficult airway management is discussed. EGA devices have saved countless lives because they facilitate ventilation when facemask ventilation and tracheal intubation were not possible. Traditionally, difficult airway management focused on successful tracheal intubation. The EGA has allowed a paradigm shift, changing the emphasis of difficult airway management from tracheal intubation to ventilation and oxygenation. EGA devices have proved to be useful adjuncts to tracheal intubation; in particular, the combination of EGA devices and fiberoptic guidance is a powerful technique for difficult airway management. Despite their utility, EGAs do have disadvantages. For example, they typically do not provide the same protection from pulmonary aspiration of regurgitated gastric material as a cuffed tracheal tube. The risk of aspiration of gastric contents persists despite advances in EGA design that have sought to address the issue. The association between excessive EGA cuff pressure and potential morbidity is becoming increasingly recognized. The widespread success and adoption of the EGA into clinical practice has revolutionized airway management and anesthetic care. Although the role of EGAs is well established, the user must know each device's particular strengths and limitations and understand that limited data are available for guidance until a new device has been well studied.


Assuntos
Anestesia , Máscaras Laríngeas , Respiração Artificial/instrumentação , Anestesia/efeitos adversos , Anestesia/história , Desenho de Equipamento , História do Século XX , História do Século XXI , Humanos , Máscaras Laríngeas/efeitos adversos , Máscaras Laríngeas/história , Seleção de Pacientes , Respiração Artificial/efeitos adversos , Respiração Artificial/história , Medição de Risco , Fatores de Risco
19.
J Am Acad Child Adolesc Psychiatry ; 61(7): 844-847, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35278631

RESUMO

As many as one-third of patients who have coronavirus disease 2019 (COVID-19) develop long-term neuropsychiatric symptoms, such as anxiety, depression, brain fog, psychosis, seizures, and suicidal behavior.1 Several case reports have demonstrated the association between psychotic symptoms following infection with COVID-19 in adults.1,2 In a first episode of psychosis, clinical findings on history, examination, and diagnostic studies may suggest that the psychotic symptoms are due to medical illness, which may be reversible. The presentation can include acute onset, predominance of visual or tactile hallucinations, and association with other neurological symptoms.3.


Assuntos
COVID-19 , Transtornos Psicóticos , Adolescente , Adulto , COVID-19/complicações , Alucinações/etiologia , Humanos , Transtornos Psicóticos/diagnóstico , SARS-CoV-2 , Ideação Suicida
20.
Biochem Biophys Res Commun ; 414(1): 79-83, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-21945434

RESUMO

Aggregation of a peptide, beta-amyloid (Aß), is a hallmark molecular process found in Alzheimer's disease (AD). During Aß aggregation, oligomeric and fibrillar Aß are formed, and these molecular self-assembly steps are implicated in generation of toxic effects in AD. Crocetin is a natural carotenoid dicarboxyl acid displaying various pharmaceutical effects and may be co-localized with Aß mediated by human serum albumin. In the study presented here, we examined the effects of crocetin on Aß aggregation in three different molecular pathways. Our results demonstrate that crocetin inhibited Aß fibril formation and destabilized pre-formed Aß fibrils. Moreover, crocetin caused stabilization of Aß oligomers and prevented their conversion into Aß fibrils. Our study reveals potential pathological and pharmaceutical implication of crocetin in AD and suggests possible application of crocetin for currently limited structural studies on unstable Aß oligomers.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Amiloide/antagonistas & inibidores , Carotenoides/farmacologia , Sequência de Aminoácidos , Amiloide/química , Peptídeos beta-Amiloides/química , Benzotiazóis , Carotenoides/química , Fluorescência , Humanos , Dados de Sequência Molecular , Tiazóis/química , Vitamina A/análogos & derivados
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