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1.
J Trauma Acute Care Surg ; 88(1): 70-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31688824

RESUMO

BACKGROUND: Identification of occult hypovolemia in trauma patients is difficult. We hypothesized that in acute trauma patients, the response of ultrasound-measured minimum inferior vena cava diameter (IVCDMIN), IVC Collapsibility Index (IVCCI), minimum internal jugular diameter (IJVDMIN) or IJV Collapsibility Index (IJVCI) after up to 1 hour of fluid resuscitation would predict 24-hour resuscitation intravenous fluid requirements (24FR). METHODS: An NTI-funded, American Association for the Surgery of Trauma Multi-Institutional Trials Committee prospective, cohort trial was conducted at four Level I Trauma Centers. Major trauma patients were screened for an IVCD of 12 mm or less or IVCCI of 50% or less on initial focused assessment sonographic evaluations for trauma. A second IVCD was obtained 40 minutes to 60 minutes later, after standard-of-care fluid resuscitation. Patients whose second measured IVCD was less than 10 mm were deemed nonrepleted (NONREPLETED), those 10 mm or greater were repleted (REPLETED). Prehospital and initial resuscitation fluids and 24FR were recorded. Demographics, Injury Severity Score, arterial blood gasses, length of stay, interventions, and complications were recorded. Means were compared by ANOVA and categorical variables were compared via χ. Receiver operating characteristic curves analysis was used to compare the measures as 24FR predictors. RESULTS: There were 4,798 patients screened, 196 were identified with admission IVCD of 12 mm or IVCCI of 50% or less, 144 were enrolled. There were 86 REPLETED and 58 NONREPLETED. Demographics, initial hemodynamics, or laboratory measures were not significantly different. NONREPLETED had smaller IVCD (6.0 ± 3.7 mm vs. 14.2 ± 4.3 mm, p < 0.001) and higher IVCCI (41.7% ± 30.0% vs. 13.2% ± 12.7%, p < 0.001) but no significant difference in IJVD or IJVCCI. REPLETED had greater 24FR than NONREPLETED (2503 ± 1751 mL vs. 1,243 ± 1,130 mL, p = 0.003). Receiver operating characteristic analysis indicates IVCDMIN predicted 24FR (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.64-0.84; p < 0.001) as did IVCCI (AUC, 0.75; 95% CI, 0.65-0.85; p < 0.001) but not IJVDMIN (AUC, 0.48; 95% CI, 0.24-0.60; p = 0.747) or IJVCI (AUC, 0.54; 95% CI, 0.42-0.67; p = 0.591). CONCLUSION: Ultrasound assessed IVCDMIN and IVCCI response initial resuscitation predicts 24-hour fluid resuscitation requirements. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

2.
Retina ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31851049

RESUMO

PURPOSE: To investigate the relationship between posterior staphyloma and dome-shaped macula (DSM) in highly myopic eyes. METHODS: The clinical data were collected from patients with high myopia: diopter, best-corrected visual acuity, axial length, fundus images, optical coherence tomography, and 3D magnetic resonance imaging. A DSM was defined as a convex curvature of the macula in one or both of the vertical and horizontal optical coherence tomography scans. The relationship between DSM and posterior staphyloma was evaluated. RESULTS: A total of 123 eyes were included. Dome-shaped macula was found in 18 eyes (14.63%). Twelve eyes with DSM had positive 3D magnetic resonance imaging findings. Nine eyes had horizontal oval-shaped dome, and a band-shaped inward convexity that extended horizontally from the optic disc through the fovea could be seen. Three eyes had round dome, and 3D magnetic resonance imaging showed a round inward convexity of the macular area. Five inward convexities were the border of multiple staphylomas, five were the boundary of one staphyloma, and two were within a single staphyloma. CONCLUSION: The formation of highly myopic DSM is related to the morphological change of the entire posterior segment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31688825

RESUMO

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS) based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including- 10 healthy controls, 19 known positive or negative controls and 327 trauma patients over 65 years of age who were evaluated at our large, urban Level 1 Trauma Center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage was compared with LCMS results to determine overall accuracy, sensitivity, specificity and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 were on DOACs (10.96%): 21 were on Apixaban, 14 on rivaroxaban and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.06%, (PPV 92.50% and NPV 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.11% (PPV 86.36% and NPV 99.40%). There were three false positive results and two false negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSIONS: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. STUDY TYPE: diagnostic test BASIC SCIENCE PAPER: therefore does not require a level of evidence.

4.
ACS Sens ; 4(12): 3240-3247, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31777244

RESUMO

A subparts per million-sensitive nitrogen dioxide (NO2) sensing circuit with improved humid air stability was realized incorporating UV-ozone treatment on a poly(bisdodecylquaterthiophene)/polystyrene blend film. The circuit consisted of a pair of organic field-effect transistors (OFETs) in series, one OFET with and one without this treatment. In contrast to most previous OFET sensors, the readout was obtained from the voltage Vout at a point between the OFETs. The circuit showed a low detection limit (200 ppb) toward NO2 and greatly reduced the voltage drift in the humid environment compared to the current drift of the circuit or the individual OFETs because of the balance of conductance drifts on either side of the readout point, which differs from the existing OFET-based sensors. By using Vout as the detection parameter, the sensitivity of the circuit approaches 25 and 400% for NO2 concentrations of 200 ppb and 20 ppm, respectively. Moreover, the Vout is substantial enough to be easily measured by a voltmeter, which could remove the need for complex equipment (semiconductor analyzer system) for the sensing test. We thus demonstrate a simplified approach to stabilized OFET circuits that could be used in printable, flexible, or wearable sensors.

5.
Ultrason Sonochem ; 59: 104703, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31421613

RESUMO

SSZ-13 zeolite has been widely used in catalysis and adsorption because of good hydrothermal stability and pore structure. However, long crystallization time is the main challenge limiting its industry application. As increased emissions and ineffective treatment, coal gangue not only occupies land, but also pollutes the waterbody and farmland. Using coal gangue as raw material to synthetize zeolite has been considered as an environmentally friendly and effective alternative to solve the issues of accumulation and pollution, which also improves the added value of coal gangue. The ultrasonic assistance has been proven to be one of the potential pretreatment methods to promote the dissolution of crystalline silicon aluminum and reduce the crystallization time of molecular sieve. In this work, SSZ-13 was synthesized by coal gangue via ultrasonic pretreatment combined with hydrothermal growth method. The ultrasonic frequency and power were 20 kHz and 120 W, respectively. The synthesized samples were characterized by XRD, SEM, EDS, BET. The results showed that the crystallization time was shorten to 18 h, which was about 12 h lower than the same conditions of conventional chemicals synthesis. Furthermore, the specific surface area of the synthesized sample was more than 620 m2/g, which also indicated over 95% NOx conversion across a broad range from 180 to 400 °C and over 94% NOx conversion at 200-400 °C after hydrothermal treatment 6 h. This study provides a reference for the environmentally friendly utilization of coal gangue and the low-cost rapid synthesis and application of SSZ-13.

6.
ACS Nano ; 13(6): 7345-7354, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31188558

RESUMO

Liver tumor is one of the most lethal cancers due to its low ratio of surgical resection, high recurrence rate, and invasiveness. Photothermal therapy (PTT) possesses many advantages for cancer therapy because of its noninvasive nature. However, most PTT is conducted in the first near-infrared (NIR-I) window, so second near-infrared (NIR-II) photosensitizers with higher penetrating ability and clinical prospects are seriously desirable. Herein, a semiconducting polymer with optimized absorption in NIR-I and NIR-II regions is obtained by ternary copolymerization methodology. The prepared nanoparticle (NP) from the semiconducting polymer is used for treatment of orthotopic liver cancer upon laser irradiation. Compared with an 808 nm laser, a 1064 nm laser leads to more effective inhibition toward orthotopic liver cancer in the same conditions. These results thus demonstrate that the NIR-II polymeric NPs may inspire another aspect for highly efficient therapy of various orthotopic cancers.

7.
PLoS One ; 14(5): e0215386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042735

RESUMO

BACKGROUND: Novel crystalloid solutions containing polyethylene glycol polymers (PEG-20k) produce dramatic resuscitation effects but dose-dependently produce a hypocoagulative state. The objective of this study was to examine possible mechanisms of this effect. Based on previous thromboelastography data, we hypothesize the effect is largely due to platelet interactions with the polymers. METHODS: Whole citrated blood from healthy volunteers was diluted ex-vivo 10% with crystalloids and tested for coagulation and platelet function. The specific tests included prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and von Willebrand factor (vWf) activity, thrombin generation, thromboelastography with and without platelet mapping, platelet flow cytometry, and erythrocyte sedimentation rate. FINDINGS: Fibrinogen and vWF activities, PT, and aPTT were not affected by PEG-20k dilutions. Thrombin activity was mildly suppressed with PEG-20k (TTP- 20%). Platelet mapping demonstrated significantly greater % inhibition of both ADP and arachidonic acid-induced platelet aggregation with PEG-20k, but direct ADP-activated gpIIa/IIIb (PAC1) and P-selectin (CD62P) binding site expression was not altered. Mild dose-dependent suppression of TEG-MA was seen with PEG-20k using platelet poor plasma. Erythrocyte Sedimentation Rates (ESR) were dramatically accelerated after dilution with 10% PEG-20k, which was competitively blocked by smaller PEG polymers, suggesting nonspecific PEG-20k cell binding effects. CONCLUSIONS: PEG-20k creates a mild hypocoagulative state in whole blood at concentrations ≥10%, which may be due to platelet-PEG interactions at the IIb/IIIa interface with lesser effects on fibrin polymerization. This interaction may cause a functional thrombasthenia induced by nonspecific platelet surface passivation by the PEG polymer.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Soluções Cristaloides/farmacologia , Polietilenoglicóis/química , Adulto , Plaquetas/fisiologia , Soluções Cristaloides/química , Relação Dose-Resposta a Droga , Feminino , Fibrinogênio/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Polietilenoglicóis/farmacologia , Ressuscitação , Tromboelastografia/efeitos dos fármacos , Adulto Jovem , Fator de von Willebrand/metabolismo
8.
Am Surg ; 85(5): 456-461, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126355

RESUMO

Estimating the prevalence of harassment, verbal abuse, and discrimination among residents is difficult as events are often under-reported. The purpose of this study was to determine the prevalence of discrimination and abuse among surgical residents using the HITS (Hurt, Insulted, Threatened with harm or Screamed at) screening tool. A multicenter, cross-sectional, survey-based study was conducted at five academic teaching hospitals. Of 310 residents, 76 (24.5%) completed the survey. The HITS screening tool was positive in 3.9 per cent. The most common forms of abuse included sexual harassment (28.9%), discrimination based on gender (15.7%), and discrimination based on ethnicity (7.9%). There was a positive correlation between individuals who reported gender discrimination and racial discrimination (r = 0.778, n = 13, P = 0.002). Individuals who experienced insults were more likely to experience physical threats (r = 0.437, n = 79, P < 0.001) or verbal abuse (r = 0.690, n = 79, P < 0.001). Discrimination and harassment among surgical residents in academic teaching hospitals across the United States is not uncommon. Further research is needed to determine the impact of these findings on resident attrition.


Assuntos
Assédio não Sexual/estatística & dados numéricos , Internato e Residência , Abuso Físico/estatística & dados numéricos , Preconceito/estatística & dados numéricos , Assédio Sexual/estatística & dados numéricos , Discriminação Social/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Inquéritos e Questionários , Estados Unidos
9.
PLoS One ; 13(11): e0207147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30439979

RESUMO

BACKGROUND: Low volume resuscitation (LVR) in shock prevents deleterious effects of crystalloid loading in pre-hospital settings. Polyethylene glycol 20,000 (PEG-20k) based LVR solutions are 20-fold more effective at maintaining perfusion and survival in shock compared to conventional crystalloids. The aim of this study was to determine coagulation and platelet function of whole blood treated with 10% PEG-20k. METHODS: Citrated blood from volunteers (n = 25) or early admission severely injured trauma patients (n = 9) were diluted 10% with various LVR solutions in a matched design with a paired volume control (saline), and studied using thromboelastography (TEG). FINDINGS: In healthy volunteers and patients, 10% PEG-20k significantly increased clot amplification time (k), decreased propagation (angle), maximal clot size and strength (MA), and the overall coagulation index (CI), but not clot initiation (R) or fibrinolysis (Ly30), relative to paired saline dilutional controls. Clinically, K, angle, and MA were just outside of the normal limits in volunteers but not in patients. No statistical differences existed between PEG-20k and Hextend (HES) in either patient population. In a dose response series using volunteer blood, all effects of 10% PEG-20k on TEG were reversed and normalized by lower concentrations (7.5% and 5%). Furthermore, 7.5% PEG-20k produced similar resuscitation effects as 10% PEG in rodent hemorrhagic shock models (n = 5). CONCLUSIONS: In conclusion, PEG-20k based LVR solutions produced a dose-dependent minor hypocoagulative state, possibly associated with changes in clot propagation and platelet function, which can be reversed by dose reduction in concentration while providing superior LVR, microvascular rescue, and lactate clearance compared to saline or starch.


Assuntos
Polietilenoglicóis/administração & dosagem , Soluções para Reidratação/administração & dosagem , Choque/terapia , Adolescente , Adulto , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Volume Sanguíneo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Fibrinólise/efeitos dos fármacos , Hidratação , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Choque Hemorrágico/tratamento farmacológico , Soluções , Tromboelastografia , Adulto Jovem
10.
Biomed Pharmacother ; 106: 941-945, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30119266

RESUMO

Betulin is a phenolic flavonoid which has been reported to possess a mass of pharmacological properties, especially anti-inflammatory activity. The purpose of this study was to explore the protective effects and possible mechanism of betulin against lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute liver injury. D-Gal and LPS were intraperitoneally injected to develop acute liver injury animal model. Betulin (2, 4 or 8 mg/kg) were given 1 h before LPS/D-Gal instillation. Liver tissues and plasma samples were collected 9 h after LPS/D-Gal were given. The results indicated that betulin dramatically decreased liver pathologic changes, myeloperoxidase (MPO) activity, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Simultaneously, the levels of interleukin (IL-1ß) and tumor necrosis factor (TNF-α) in serum and liver tissues were both attenuated by betulin. Besides, betulin suppressed NF-κB pathway activation in a dose-dependently manner. Betulin increased the expression of PPAR-γ in a dose-dependent manner. In conclusion, all these results revealed that betulin could possess potential therapeutic effect for LPS/D-Gal-induced acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Galactosamina , Lipopolissacarídeos , Fígado/efeitos dos fármacos , PPAR gama/agonistas , Triterpenos/farmacologia , Alanina Transaminase/sangue , Animais , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interleucina-1beta/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , PPAR gama/metabolismo , Peroxidase/sangue , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
11.
Oncol Res ; 26(5): 765-773, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-28810933

RESUMO

MicroRNA-152 (miR-152) expression has been reported to be downregulated in osteosarcoma (OS). However, the role of miR-152 in OS is not well documented. In the present study, we aimed to explore the function and underlying mechanism of miR-152 in OS. We found that miR-152 was underexpressed in OS tissues and cell lines. Decreased miR-152 was inversely correlated with lymph node metastasis and advanced clinical stage. Overexpression of miR-152 significantly inhibited cell proliferation, colony formation, migration, and invasion of OS cells. Bioinformatics analyses showed that miR-152 directly targeted E2F transcription factor 3 (E2F3), as further confirmed by a dual-luciferase reporter assay. E2F3 expression was upregulated and inversely correlated with miR-152 expression level in human OS tissues. Moreover, the inhibitory effects of miR-152 on OS growth and invasion were attenuated by E2F3 overexpression. Taken together, our findings indicated that miR-152 reduced OS growth and invasion by targeting E2F3 and provided new evidence of miR-152 as a potential therapeutic target for OS.


Assuntos
Neoplasias Ósseas/patologia , Fator de Transcrição E2F3/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Movimento Celular/genética , Proliferação de Células/genética , Fator de Transcrição E2F3/genética , Humanos , Invasividade Neoplásica/patologia , Osteossarcoma/genética
12.
J Cell Biochem ; 119(6): 4742-4750, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29280192

RESUMO

Oligodendrocytes (OLs) are glial cells that form myelin sheaths in the central nervous system. Myelin sheath plays important role in nervous system and loss of it in neurodegenerative diseases can lead to impairment of movement. Understanding the signals and factors that regulate OL differentiation can help to address novel strategies for improving myelin repair in neurodegenerative diseases. The aim of this study was to investigate the role of insulin-like growth factor-binding proteins 7 (IGFBP-7) in differentiating OL precursor cells (OPCs). It was found that oligodendrocyte precursors undergoing differentiation were accompanied by selective expression of IGFBP-7. In addition, knockdown of IGFBP-7 promoted differentiation of oligodendrocytes and increased formation of myelin in cultured cells. In contrast, excessive expression of IGFBP-7 inhibited differentiation of oligodendrocytes. Furthermore, overexpression of IGFBP-7 in oligodendrocyte precursor cells increased transcription of Wnt target genes and promoted ß-Catenin nuclear translocation. These findings suggest that IGFBP-7 negatively regulates differentiation of oligodendrocyte precursor cells via regulation of Wnt/ß-Catenin signaling.


Assuntos
Diferenciação Celular , Regulação da Expressão Gênica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/biossíntese , Células-Tronco Neurais/metabolismo , Oligodendroglia/metabolismo , Via de Sinalização Wnt , Animais , Células HEK293 , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Células-Tronco Neurais/citologia , Oligodendroglia/citologia , Ratos , Ratos Sprague-Dawley , beta Catenina/genética , beta Catenina/metabolismo
13.
J Trauma Acute Care Surg ; 82(3): 451-460, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28225738

RESUMO

BACKGROUND: Our group has previously published a retrospective review defining variables predictive of transmural bowel ischemia in the setting of pneumatosis intestinalis (PI). We hypothesize this prospective study will confirm the findings of the retrospective review, enhancing legitimacy to the predictive factors for pathologic PI previously highlighted. METHODS: Data were collected using the Research Electronic Data Capture. Forward logistic regression was utilized to identify independent predictors for pathologic PI. Statistical significance was defined as p ≤ 0.05. RESULTS: During the 3-year study period, 127 patients with PI were identified. Of these, 79 had benign disease, and 49 pathologic PI defined by the presence of transmural ischemia during surgical exploration or autopsy. Laboratory values such as elevated international normalized ratio (INR), decreased hemoglobin, and a lactate value of greater than 2.0 mmol/L were predictive of pathologic PI, as well as clinical factors including adynamic ileus, peritoneal signs on physical examination, sepsis, and hypotension. The location was also a significant factor, as patients with small bowel PI had a higher incidence of transmural ischemia than colonic PI. On multiple logistic regression, lactate value of greater than 2.0 mmol/L (odds ratio, 5.1, 1.3-19.5; p = 0.018), elevated INR (odds ratio, 3.2, 1.1-9.6; p = 0.031), peritonitis (15.0, 2.9-78; p = 0.001), and decreased hemoglobin (0.70, 0.50-0.97, 0.031) remained significant predictors of transmural ischemia (area under the curve, 0.90; 0.83-0.97). A lactate value of 2.0 mmol/L or greater and peritonitis are common factors between the retrospective review and this prospective study. CONCLUSIONS: We recommend surgical exploration to be strongly considered for those PI patients presenting also with a lactate greater than 2 mmol/L and/or peritonitis. We suggest strong suspicion for necrosis in those patient with PI and small bowel involvement, ascites on computed tomography scan, adynamic ileus, anemia, and a high INR. LEVEL OF EVIDENCE: Prognostic study, level II; therapeutic study, level II.


Assuntos
Pneumatose Cistoide Intestinal/epidemiologia , Adulto , Idoso , Ascite/diagnóstico por imagem , Biomarcadores/análise , Feminino , Hemoglobinas/análise , Humanos , Coeficiente Internacional Normatizado , Intestino Delgado/patologia , Isquemia/diagnóstico , Lactatos/análise , Masculino , Pessoa de Meia-Idade , Necrose , Peritonite/diagnóstico , Pneumatose Cistoide Intestinal/diagnóstico , Pneumatose Cistoide Intestinal/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Tomografia Computadorizada por Raios X
14.
Neurosci Lett ; 631: 7-12, 2016 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-27497920

RESUMO

Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment. The hippocampus was harvested to determine the levels of interleukin (IL)-6, IL-1ß, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine (5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like behaviors presented on 7days and lasted to at least 14days after the CFA injection. Single dose of ketamine at 20mg/kg relieved both the mechanical allodynia and the associated depression-like behaviors as demonstrated by the attenuated mechanical withdrawal threshold, reduced immobility time in the forced swim test, and increased sucrose preference after ketamine treatment. The total distance had no significant change after the CFA injection or ketamine treatment in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL-1ß, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate mechanical allodynia and consequent depression-like behaviors and down-regulate hippocampal proinflammatory responses and IDO/KYN signal pathway in rats.


Assuntos
Antidepressivos/administração & dosagem , Depressão/prevenção & controle , Hiperalgesia/prevenção & controle , Inflamação/complicações , Ketamina/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Depressão/complicações , Modelos Animais de Doenças , Adjuvante de Freund , Hipocampo/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/complicações , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Cinurenina/metabolismo , Masculino , Nociceptividade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Triptofano/metabolismo
15.
J Trauma Acute Care Surg ; 81(3): 541-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27270856

RESUMO

BACKGROUND: Variability exists in the approach to cervical spine (c-spine) clearance after significant trauma. Using concurrently gathered data on more than 9,000 such patients, the current study develops an evidence-based and readily adoptable algorithm for c-spine clearance aimed at timely removal of collar, optimal use of imaging, and appropriate spine consultations. METHODS: Prospective study of adult blunt trauma team alert (TTA) patients presenting at a Level I trauma center who underwent screening computed tomography (CT) to diagnose/rule out c-spine injury (January 2008 to May 2014). Regression analysis comparing patients with and without c-spine injury-fracture and/or ligament-was used to identify significant predictors of injury. The predictors with the highest odds ratio were used to develop the algorithm. RESULTS: Among 9,227 patients meeting inclusion criteria, c-spine injury was identified in 553 patients (5.99%). All 553 patients had a c-spine fracture, and of these, 57 patients (0.6% of entire population and 10.31% of patients with injury) also had a ligamentous injury. No patient with a normal CT result was found to have an injury. The five greatest predictors of ligament injury that follow were used to develop the algorithm: (1) CT evidence of ligament injury; (2) fracture pattern "not" isolated transverse/spinous process; (3) neurologic symptoms; (4) midline tenderness; and (5) Glasgow Coma Scale score <15. CONCLUSION: TTA patients should undergo screening c-spine CT to rule out injury. Most patients will have a negative CT and can have their collars removed. A select group of patients will require collars and spine consultation and a smaller subset of magnetic resonance imaging to rule out ligament injury. LEVEL OF EVEDINCE: Therapeutic study, level III.


Assuntos
Algoritmos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Escala de Coma de Glasgow , Humanos , Ligamentos/lesões , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos , Centros de Traumatologia
16.
Oncol Rep ; 36(1): 542-50, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27221209

RESUMO

MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética
18.
Surg Infect (Larchmt) ; 16(4): 361-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26207396

RESUMO

BACKGROUND: Linezolid is associated infrequently with bone marrow suppression in immunocompetent patients, but hematologic complications from linezolid in transplant recipients are understudied. This study evaluated the hematologic safety of linezolid in solid organ transplant recipients. METHODS: We performed a retrospective study of inpatients at our institution treated with linezolid from June 1, 2009 until June 6, 2012. The solid organ transplant cohort (TP) was compared with the non-transplant cohort (NTP) using parameters related to linezolid safety. Outcomes included incidences of leukopenia or thrombocytopenia at the end of linezolid treatment (EOT), lengths of stay, and blood product requirements. RESULTS: The TP cohort included 110 patients; the NTP cohort included 583 patients. Baseline parameters were similar between the TP and NTP cohorts. Non-transplant patients were more likely to have methicillin-resistant Staphylococcus aureus (MRSA), whereas TP patients received more doses of linezolid (17.0 vs. 11.3, p<0.001) and were more likely to receive other drugs associated with thrombocytopenia (91.7% vs. 11.3%, p<0.0001). Transplant patients with normal platelet counts at baseline were more likely to have EOT thrombocytopenia (29.3% vs. 10.7%, p=0.005), and multivariable regression analysis confirmed only a beginning platelet count less than 150,000 platelets per micoliter to be significantly different between groups: 43% TP versus 26.9% NTP (p=0.0009) making it the only independent predictor of EOT thrombocytopenia. Finally, TP patients were more likely to require platelet transfusions compared with the NTP cohort. CONCLUSIONS: Transplant patients who received linezolid had a higher incidence of EOT thrombocytopenia and platelet transfusions, compared with NTP. Transplant patients who are thrombocytopenic at baseline are at the greatest risk. These findings may relate to more frequent use of drugs associated with marrow suppression or greater linezolid exposure in the TP cohort. Clinicians caring for transplant patients should take into account this higher risk of thrombocytopenia and need for platelets when considering use of linezolid in this population.


Assuntos
Antibacterianos/efeitos adversos , Linezolida/efeitos adversos , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Tempo de Internação , Linezolida/administração & dosagem , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Transplante de Órgãos/estatística & dados numéricos , Estudos Retrospectivos , Trombocitopenia/mortalidade , Resultado do Tratamento , Enterococos Resistentes à Vancomicina
19.
J Trauma Acute Care Surg ; 79(1): 10-4; discussion 14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26091308

RESUMO

BACKGROUND: Recent military studies demonstrated an association between prehospital tourniquet use and increased survival. The benefits of this prehospital intervention in a civilian population remain unclear. The aims of our study were to evaluate tourniquet use in the civilian population and to compare outcomes to previously published military experience. We hypothesized that incorporation of tourniquet use in the civilian population will result in an overall improvement in mortality. METHODS: This is a preliminary multi-institutional retrospective analysis of prehospital tourniquet (MIA-T) use of patients admitted to nine urban Level 1 trauma centers from January 2010 to December 2013. Patient demographics and mortality from a previous military experience by Kragh et al. (Ann Surg. 2009;249:1-7) were used for comparison. Patients younger than 18 years or with nontraumatic bleeding requiring tourniquet application were excluded. Data were analyzed using a two-tailed unpaired Student's t test with p < 0.05 as significant. RESULTS: A total of 197 patients were included. Tourniquets were applied effectively in 175 (88.8%) of 197 patients. The average Injury Severity Score (ISS) for MIA-T versus military was 11 ± 12.5 versus 14 ± 10.5, respectively (p = 0.02). The overall mortality and limb amputation rates for the MIA-T group were significantly lower than previously seen in the military population at 6 (3.0%) of 197 versus 22 (11.3%) of 194 (p = 0.002) and 37 (18.8%) of 197 versus 97 (41.8%) of 232 (p = 0.0001), respectively. CONCLUSION: Our study is the largest evaluation of prehospital tourniquet use in a civilian population to date. We found that tourniquets were applied safely and effectively in the civilian population. Adaptation of this prehospital intervention may convey a survival benefit in the civilian population. LEVEL OF EVIDENCE: Epidemiologic study, level V.


Assuntos
Serviços Médicos de Emergência , Torniquetes , Ferimentos e Lesões/terapia , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/fisiopatologia , Ferimentos Penetrantes/mortalidade , Ferimentos Penetrantes/fisiopatologia , Ferimentos Penetrantes/terapia
20.
Surg Infect (Larchmt) ; 16(4): 455-60, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26069992

RESUMO

BACKGROUND: Fulminant Clostridium difficile colitis (fCDC) is a highly lethal disease with mortality rates ranging between 12% and 80%. Although often these patients require a total abdominal colectomy (TAC) with ileostomy, there is no established management protocol for post-operative antibiotics. In this study we aim to make some recommendations for post-operative antibiotic usage, while describing the practice across different institutions. METHODS: Multi-institutional retrospective case series including fCDC patients who underwent a TAC between January 1, 2007, and June 30, 2012. We first analyzed the complete cohort and consecutively performed a survivor analysis, comparing different antibiotic regimens. Additionally we stratified by time interval (antibiotics for ≤7 d, or ≥8 d). Primary outcome was in-hospital mortality. Additional secondary outcomes included hospital length of stay (HLOS), ICU LOS, number of ventilator-free days, and occurrence of intra-abdominal complications (proctitis, abscess, sepsis, etc.). RESULTS: A total of 100 fCDC patients that underwent a TAC were included across five institutions. Four different antibiotic regimens were compared; A (metronidazole IV+vancomycin PO), B (metronidazole IV), C (metronidazole IV+vanco PO and PR), and D (metronidazole IV+vancomycin PR). The combination of IV metronidazole with or without PO vancomycin showed superior outcomes in terms of a shorter ICU length of stay and more ventilator-free days. However, when comparing metronidazole alone vs. metronidazole and any combination of vancomycin, no significant differences were found. Neither the addition of vancomycin enema, nor the time interval changed outcomes. CONCLUSION: Patients, after a TAC for fCDC, may be placed on either IV metronidazole or PO vancomycin depending upon local antibiograms, and proctitis may be treated with the addition of a vancomycin enema (PR). There was no data to support routine treatment of more than 7 d.


Assuntos
Antibacterianos/uso terapêutico , Clostridium difficile , Colectomia/efeitos adversos , Enterocolite Pseudomembranosa , Ileostomia/efeitos adversos , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
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