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Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.
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Hemostasis , Hepatopatías , Biopsia , Hemorragia/etiología , Hemostasis/fisiología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hepatopatías/patología , Ultrasonografía , Ultrasonografía Doppler en Color/efectos adversosRESUMEN
Colloidal dispersions with liquid crystallinity hold great promise for fabricating their superstructures. As an example, when graphene oxide (GO) sheets are assembled in the liquid crystalline state, they can turn into ordered macroscopic forms of GO such as fibers via the wet spinning process. Here, we report that by reinforcing intersheet interactions, GO liquid crystals (LCs) turn into mechanically robust hydrogels that can be readily drawn into highly aligned fibrillar structures. GO hydrogel fibers with highly aligned sheets (orientation factor, f = 0.71) exhibit more than twice the ionic conductivity compared to those with partially aligned structures (f = 0.01). The hierarchically interconnected two-dimensional nanochannels within these neatly aligned GOLC hydrogel fibers may facilitate controlled transport of charge carriers and could be potentially explored as cables for interconnecting biosystems and/or human-made devices.
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OBJECTIVE: This study was conducted to evaluate various levels of milk by-product in weaning pig diet on growth performance, blood profiles, carcass characteristics and economic performance for weaning to finishing pigs. METHODS: A total of 160 weaning pigs ([Yorkshire×Landrace]×Duroc), average 7.01±1.32 kg body weight (BW), were allotted to four treatments by BW and sex in 10 replications with 4 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with various levels of milk by-product (Phase 1: 0%, 10%, 20%, and 30%, Phase 2: 0%, 5%, 10%, and 15%, respectively). During weaning period (0 to 5 week), weaning pigs were fed experimental diets and all pigs were fed the same commercial feed during growing-finishing period (6 to 14 week). RESULTS: In the growth trial, BW, average daily gain (ADG), and average daily feed intake (ADFI) in the nursery period (5 weeks) increased as the milk by-product level in the diet increased (linear, p<0.05). Linear increases of pig BW with increasing the milk product levels were observed until late growing period (linear, p = 0.01). However, there were no significant differences in BW at the finishing periods, ADG, ADFI, and gain:feed ratio during the entire growing-finishing periods. The blood urea nitrogen concentration had no significant difference among dietary treatments. High inclusion level of milk by-product in weaner diet decreased crude protein (quadratic, p = 0.05) and crude ash (Linear, p = 0.05) of Longissimus muscle. In addition, cooking loss and water holding capacity increased with increasing milk product levels in the weaner diets (linear, p<0.01; p = 0.05). High milk by-product treatment had higher feed cost per weight gain compared to non-milk by-products treatment (linear, p = 0.01). CONCLUSION: Supplementation of 10% to 5% milk by-products in weaning pig diet had results equivalent to the 30% to 15% milk treatment and 0% milk by-product supplementation in the diet had no negative influence on growth performance of finishing pigs.
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Frataxin is a mitochondrial protein whose deficiency is the cause of Friedreich's ataxia, a hereditary neurodegenerative disease. This protein plays a role in iron-sulfur cluster biosynthesis, protection against oxidative stress and iron metabolism. In an attempt to provide a better understanding of the role played by metals in its metabolic functions, the mechanisms of mitochondrial metal binding to frataxin in vitro have been investigated. A purified recombinant yeast frataxin homolog Yfh1 binds two Cu(ii) ions with a Kd1(CuII) of 1.3 × 10-7 M and a Kd2(CuII) of 3.1 × 10-4 M and a single Cu(i) ion with a higher affinity than for Cu(ii) (Kd(CuI) = 3.2 × 10-8 M). Mn(ii) forms two complexes with Yfh1 (Kd1(MnII) = 4.0 × 10-8 M; Kd2(MnII) = 4.0 × 10-7 M). Cu and Mn bind Yfh1 with higher affinities than Fe(ii). It is established for the first time that the mechanisms of the interaction of iron and copper with frataxin are comparable and involve three kinetic steps. The first step occurs in the 50-500 ms range and corresponds to a first metal uptake. This is followed by two other kinetic processes that are related to a second metal uptake and/or to a change in the conformation leading to thermodynamic equilibrium. Frataxin deficient Δyfh1 yeast cells exhibited a marked growth defect in the presence of exogenous Cu or Mn. Mitochondria from Δyfh1 strains also accumulated higher amounts of copper, suggesting a functional role of frataxin in vivo in copper homeostasis.
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Cobre/metabolismo , Hierro/metabolismo , Mitocondrias/metabolismo , Saccharomyces cerevisiae/metabolismo , Homeostasis , Proteínas de Unión a Hierro/metabolismo , Cinética , Estrés Oxidativo , Saccharomyces cerevisiae/crecimiento & desarrollo , Termodinámica , FrataxinaRESUMEN
BACKGROUND: Burn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. METHODS: Twenty adults, aged 23-58 yr, with 27-81% total body surface area (TBSA) burn, were studied at 4-57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg(-1) was given i.v. as a single bolus within 10 s. Blood samples (n=20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration-time profiles for burns and non-burns. RESULTS: A three-compartment model best described vecuronium concentration-time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min(-1), P<0.0001), which yielded shorter elimination half-life for vecuronium (5.5 vs 6.6 h, P<0.001). BURN was the single most significant covariate that explained the altered vecuronium disposition in burns. CONCLUSIONS: The altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.
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Quemaduras/fisiopatología , Bloqueantes Neuromusculares/farmacocinética , Bromuro de Vecuronio/farmacocinética , Adulto , Quemaduras/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bloqueantes Neuromusculares/sangre , Bromuro de Vecuronio/sangre , Adulto JovenRESUMEN
We report a direct measurement of the low-frequency optical conductivity of large-area single-crystal herbertsmithite, a promising spin-liquid candidate material, by means of terahertz time-domain spectroscopy. In the spectral range below 1.4 THz, we observe a contribution to the real part of the in-plane conductivity σ(ab)(ω) from the spin degree of freedom. This spin-induced conductivity exhibits a power-law dependence on frequency σ(ab)(ω) ~ ω(ß) with ß ≈ 1.4. Our observation is consistent with the theoretically predicted low-frequency conductivity arising from an emergent gauge field of a gapless U(1) Dirac spin liquid.
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PURPOSE: Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. METHODS: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). RESULTS: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. CONCLUSION: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.
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Antineoplásicos/efectos adversos , Corazón/efectos de los fármacos , Neoplasias Hematológicas/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Antígeno Ki-1/metabolismo , Síndrome de QT Prolongado/inducido químicamente , Adulto , Anciano , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Brentuximab Vedotina , Cardiotoxinas/efectos adversos , Cardiotoxinas/uso terapéutico , Hipersensibilidad a las Drogas/inmunología , Electrocardiografía Ambulatoria/efectos de los fármacos , Femenino , Corazón/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/fisiopatología , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/fisiopatología , Humanos , Inmunoconjugados/sangre , Inmunoconjugados/farmacocinética , Inmunoconjugados/uso terapéutico , Antígeno Ki-1/sangre , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Índice de Severidad de la Enfermedad , Adulto JovenAsunto(s)
Migración de Cuerpo Extraño/cirugía , Hematoma Espinal Epidural/etiología , Estimulación de la Médula Espinal/instrumentación , Traumatismos de la Espalda/cirugía , Traumatismos de la Espalda/terapia , Electrodos Implantados/efectos adversos , Migración de Cuerpo Extraño/diagnóstico , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Manejo del Dolor , Estimulación de la Médula Espinal/efectos adversosRESUMEN
BACKGROUND: Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. METHODS: Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. RESULTS: Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. CONCLUSIONS: The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.
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Quemaduras/fisiopatología , Isoquinolinas/farmacología , Unión Neuromuscular/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/farmacología , Adolescente , Adulto , Quemaduras/enzimología , Quemaduras/cirugía , Butirilcolinesterasa/sangre , Estudios de Casos y Controles , Estimulación Eléctrica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mivacurio , Unión Neuromuscular/fisiopatologíaRESUMEN
The human Fc receptor, FcgammaRIIA, is known to mediate phagocytosis and endocytosis, yet the greatest numbers of these receptors are expressed on the surface of non-phagocytic platelets, where they are involved in serotonin secretion. FcgammaRIIA harbours three tyrosine (Y) residues within its cytoplasmic domain. Y1 is upstream of both Y2 and Y3, which are contained within an immunoreceptor tyrosine-based activation motif (ITAM), required for many signaling events. We have demonstrated that the two ITAM tyrosines are required for phagocytic signaling and that mutation of a single ITAM tyrosine decreases but does not abolish phagocytic signaling. Furthermore, we have identified that the YMTL motif is required for endocytosis. These observations suggest that FcgammaRIIA utilizes different sequences for various signaling events. Therefore, we investigated the sequence requirements for another important FcgammaRIIA-mediated signaling event, serotonin secretion, using Rat Basophilic Leukemia (RBL-2H3) cells transfected with wildtype (WT) FcgammaRIIA or mutant FcgammaRIIA. Stimulation of cells expressing WT FcgammaRIIA induced release of serotonin at a level 7-fold greater than that in nonstimulated WT FcgammaRIIA-transfected cells or nontransfected RBL cells. Mutation of either ITAM tyrosine (Y2 or Y3) to phenylalanine was sufficient to abolish serotonin secretion. Further, while inhibition of Syk with piceatannol blocked phagocytosis as expected, it did not inhibit serotonin secretion. Additionally, inhibition of phosphoinositol-3-kinase (PI3K) with wortmannin only had a partial effect on serotonin signaling, despite the fact that the concentrations used completely abolished phagocytic signaling. These data suggest that the requirements for serotonin secretion differ from those for phagocytosis mediated by FcgammaRIIA.
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Plaquetas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de IgG/metabolismo , Serotonina/metabolismo , Transducción de Señal/fisiología , Animales , Línea Celular Tumoral , Citoplasma/metabolismo , Fagocitosis/fisiología , Proteínas Tirosina Quinasas/metabolismo , Ratas , TransfecciónRESUMEN
We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.
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Vacunas contra el Cáncer/administración & dosificación , Leucemia Experimental/terapia , Neoplasias Experimentales/terapia , Secuencia de Aminoácidos , Animales , Antígenos de Neoplasias/administración & dosificación , Antígenos de Neoplasias/genética , Secuencia de Bases , Trasplante de Médula Ósea , Ligando de CD40/administración & dosificación , Ligando de CD40/genética , Vacunas contra el Cáncer/genética , Línea Celular Tumoral , Cartilla de ADN/genética , Genes abl , Inmunización Secundaria , Leucemia Experimental/genética , Leucemia Experimental/inmunología , Depleción Linfocítica , Linfopenia/etiología , Linfopenia/inmunología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Neoplasias Experimentales/inmunología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Irradiación Corporal TotalRESUMEN
MK-0493 is a novel, potent, and selective agonist of the melanocortin receptor 4 (MC4R), one of the best-validated genetic targets and considered one of the most promising for the development of antiobesity therapeutics. An ad libitum energy-intake model was qualified with excellent reproducibility: the geometric mean ratio (GMR) with 95% confidence interval (CI) for total energy intake over a period of 24 h for 30 mg sibutramine/placebo was 0.82 (0.76, 0.88), and for 10 mg sibutramine/placebo it was 0.98 (0.91, 1.05). MK-0493 showed a small and marginally significant effect on 24-h energy intake, whereas 30 mg of sibutramine caused a significant reduction in total 24-h energy intake; specifically, the GMR (95% CI) for 30 mg sibutramine/placebo was 0.79 (0.74, 0.85). MK-0493 was associated with modest weight reduction from baseline but had only small, statistically insignificant effects relative to placebo after 12 weeks in a fixed-dose study and also after 18 weeks of stepped-titration dosing. We conclude that agonism of MC4R is not likely to represent a viable approach to the development of antiobesity therapeutics.
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Acetamidas/uso terapéutico , Depresores del Apetito/uso terapéutico , Apetito/efectos de los fármacos , Ciclobutanos/uso terapéutico , Ingestión de Energía/efectos de los fármacos , Obesidad/tratamiento farmacológico , Pirrolidinas/uso terapéutico , Receptor de Melanocortina Tipo 4/agonistas , Pérdida de Peso/efectos de los fármacos , Acetamidas/efectos adversos , Acetamidas/farmacocinética , Adulto , Anciano , Depresores del Apetito/efectos adversos , Depresores del Apetito/farmacocinética , Estudios Cruzados , Método Doble Ciego , Inglaterra , Humanos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Pirrolidinas/efectos adversos , Pirrolidinas/farmacocinética , Receptor de Melanocortina Tipo 4/metabolismo , Factores de Tiempo , Insuficiencia del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
The cyclic ether 1,4-dioxane is a synthetic industrial chemical that is used as a solvent in producing paints and lacquers. The EPA and the International Agency for Research on Cancer(IARC) classified 1,4-dioxane as a GROUP B2(probable human) carcinogen. 1,4-dioxane is also produced as a by-product during the manufacture of polyester. In this research, a polyester manufacturing company (i.e. K Co.) in Gumi, Korea was investigated regarding the release of high concentrations of 1,4-dioxane (about 600 mg/L) and whether treatment prior to release should occur to meet with the level of the regulation standard (e.g., 5 mg/L in 2010). A 10 ton/day pilot-scale treatment system using photo-Fenton oxidation was able to remove approximately 90% of 1,4-dioxane under the conditions that concentrations of 2800 ppm H(2)O(2) and 1,400 ppm FeSO(4) were maintained along with 10 UV-C lamps (240 microW/cm(2)) installed and operated continuously during aeration. However, the effluent concentration of 1,4-dioxane was still high at about 60 mg/L where TOC concentration in the effluent had been moreover increased due to decomposed products such as aldehydes and organic acids. Thus, further investigation is needed to see whether the bench scale (reactor volume, 8.9 L) of activated sludge could facilitate the decomposition of 1,4-dioxane and their by-products (i.e., TOC). As a result, 1,4-dioxane in the effluent has been decreased as low as 0.5 mg/L. The optimal conditions for the activated sludge process that were obtained are as follows: DO, 3-3.5 mg/L; HRT, 24 h; SRT 15 d; MLSS, 3,000 mg/L. Consequently, photo-Fenton oxidation coupled with activated sludge can make it possible to efficiently decompose 1,4-dioxane to keep up with that of the regulation standard.
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Dioxanos/química , Peróxido de Hidrógeno/química , Residuos Industriales , Hierro/química , Poliésteres/química , Aguas del Alcantarillado , Eliminación de Residuos Líquidos/instrumentación , Eliminación de Residuos Líquidos/métodos , Oxidación-Reducción , Procesos Fotoquímicos , Temperatura , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/químicaRESUMEN
BACKGROUND: Burn injury leads to resistance to the effects of non-depolarizing muscle relaxants. We tested the hypothesis that a larger bolus dose is as effective as priming for rapid onset of paralysis after burns. METHODS: Ninety adults, aged 18-59 yr with 40 (2)% [mean (SE)] burn and 30 (2) days after injury, received rocuronium as a priming dose followed by bolus (0.06+0.94 mg kg(-1)), or single bolus of either 1.0 or 1.5 mg kg(-1). Sixty-one non-burned, receiving 1.0 mg kg(-1) as a primed (0.06+0.94 mg kg(-1)) or full bolus dose, served as controls. Acceleromyography measured the onset times. RESULTS: Priming when compared with 1.0 mg kg(-1) bolus in burned patients shortened the time to first appearance of twitch depression (30 vs 45 s, P<0.05) and time to maximum twitch inhibition (135 vs 210 s, P<0.05). The onset times between priming and higher bolus dose (1.5 mg kg(-1)) were not different (30 vs 30 s for first twitch depression and 135 vs 135 s for maximal depression, respectively). The onset times in controls, however, were significantly (P<0.05) faster than burns both for priming and for full bolus (15 and 15 s, respectively, for first twitch depression and 75 and 75 s for maximal depression). Priming caused respiratory distress in 10% of patients in both groups. Intubating conditions in burns were significantly better with 1.5 mg kg(-1) than with priming or full 1.0 mg kg(-1) bolus. CONCLUSIONS: A dose of 1.5 mg kg(-1) not only produces an initial onset of paralysis as early as 30 s, which we speculate could be a reasonable onset time for relief of laryngospasm, but also has an onset as fast as priming with superior intubating conditions and no respiratory side-effects.
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Androstanoles/administración & dosificación , Quemaduras/fisiopatología , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Adulto , Anciano , Androstanoles/efectos adversos , Androstanoles/farmacología , Quemaduras/cirugía , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Bloqueo Neuromuscular/efectos adversos , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/fisiopatología , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Fármacos Neuromusculares no Despolarizantes/farmacología , Estudios Prospectivos , Insuficiencia Respiratoria/inducido químicamente , Rocuronio , Factores de Tiempo , Adulto JovenRESUMEN
The hypothalamic paraventricular nucleus (PVN) is composed of functionally heterogeneous cell groups, possessing distinct electrophysiological properties depending on their functional roles. Previously, T-type Ca(2+) dependent low-threshold spikes (LTS) have been demonstrated in various PVN neuronal types, including preautonomic cells. However, the molecular composition and functional properties of the underlying T-type Ca(2+) channels have not been characterized. In the present study, we combined single cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and patch-clamp recordings to identify subtypes of T-type Ca(2+) channels expressed in PVN cells displaying LTS (PVN-LTS), including identified preautonomic neurons. LTS appeared at the end of hyperpolarizing pulses either as long-lasting plateaus or as short-lasting depolarizing humps. LTS were mediated by rapidly activating and inactivating T-type Ca(2+) currents and were blocked by Ni(2+). Single cell RT-PCR and immunohistochemical studies revealed Cav3.1 (voltage-gated Ca(2+) channel) as the main channel subunit detected in PVN-LTS neurons. In conclusion, these data indicate that Cav3.1 is the major subtype of T-type Ca(2+) channel subunit that mediates T-type Ca(2+) dependent LTS in PVN neurons.
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Potenciales de Acción/fisiología , Canales de Calcio Tipo T/metabolismo , Neuronas/fisiología , Núcleo Hipotalámico Paraventricular/citología , Animales , Mapeo Encefálico , Canales de Calcio Tipo T/clasificación , Canales de Calcio Tipo T/genética , Toxina del Cólera/metabolismo , Interacciones Farmacológicas , Estimulación Eléctrica/métodos , Técnicas In Vitro , Masculino , Neuronas/efectos de los fármacos , Neuronas/efectos de la radiación , Níquel/farmacología , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Bloqueadores de los Canales de Sodio/farmacología , Tetrodotoxina/farmacologíaRESUMEN
BACKGROUND: Many pathophysiologic alterations in major burns can cause changes in the distribution of, and perhaps response to, drugs commonly used in anesthesia practice. This study was conducted to assess changes in bispectral index (BIS) caused by increasing the target propofol effect-site concentration during a target-controlled infusion (TCI) in major burns. METHODS: Eighteen patients, ASA physical status 2 or 3, aged from 20 to 55 years old, weighing 50-70 kg, with major burns, scheduled for elective early escharectomy less than a week after injury were recruited. A further 18 ASA physical status class 1 or 2, non-burns, age, sex- and weight-matched adult patients scheduled for elective surgery under general anesthesia were recruited as controls. During anesthesia induction, target propofol effect-site concentrations were increased by increments of 0.5 microg ml(-1) up to 4.5 microg ml(-1). The BIS responses to each target concentration using TCI were compared in both groups. RESULTS: In the burns group, significantly greater BIS values relating to increasing propofol TCI were noted at deeper anesthesia when compared with controls; at > or =3.5 microg ml(-1); mean BIS remained at a plateau of about 50. Patients with burns had higher cardiac indices, and lower hemoglobin and albumin concentrations than the controls. They consumed more vecuronium to maintain the same degree of neuromuscular blockade than the controls. CONCLUSIONS: In major burns, the final biphasic BIS responses appeared to be determined by numerous other variables such as BIS algorithm, TCI performance, and altered propofol pharmacokinetics and pharmacodynamics. According to our results the importance of an individually tailored approach, including careful anesthetic titration, based upon the patient's clinical condition and responses can not be overemphasized.
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Anestésicos Intravenosos/uso terapéutico , Quemaduras/complicaciones , Electroencefalografía/efectos de los fármacos , Dolor/tratamiento farmacológico , Dolor/etiología , Propofol/uso terapéutico , Adulto , Algoritmos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/farmacocinética , Quemaduras/fisiopatología , Cuidados Críticos , Femenino , Hemodinámica/efectos de los fármacos , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Propofol/administración & dosificación , Propofol/farmacocinéticaRESUMEN
BACKGROUND: Stellate ganglion block (SGB) is most commonly performed at the transverse process of the sixth cervical vertebra, the identification of which could be difficult in patients with short and wide necks. This study was conducted to evaluate whether the neck skin crease is a reliable indicator of the C6 level. METHODS: Forty-nine relatively obese pain clinic patients were investigated. They assumed a standard position for SGB. A radiopaque wire was placed along the neck skin crease caudad to the thyroid cartilage. Next, a radiopaque indicator was placed on the skin above the tubercle found to be most prominent by palpation. X-rays of the neck were obtained after each procedure. RESULTS: The probability that the neck crease would cross C5, C6 and C7 was 16%, 71%, and 12%, respectively. The most prominent tubercle corresponded to the C5, C6 and C7 levels in 16%, 69% and l4% of cases, respectively. CONCLUSION: The studied means to identify the C6 transverse process was found to correlate well with each other (P<0.001). Since in 30% of cases the C6 process could not be identified by any of the studied means, radiological guidance is recommended in order to ensure optimal safety and efficacy of SGB in selected cases.
Asunto(s)
Bloqueo Nervioso Autónomo/métodos , Vértebras Cervicales/diagnóstico por imagen , Cuello/patología , Obesidad/patología , Ganglio Estrellado , Humanos , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Obesidad/diagnóstico por imagen , RadiografíaRESUMEN
Thrombopoietin (TPO) is one of the most promising stimulants for ex vivo expansion of haematopoietic stem cells. Previously, we have found that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of human cord blood (CB) CD34+ cells and that the TPO-induced apoptotic cells belong to megakaryocyte (MK) lineage. In this study, we have examined the maturation of MK and platelet production in association with the TPO-induced apoptosis. CD34+ cells, purified from human CB, were expanded in serum-free conditions stimulated with TPO. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) assay and electron microscopy (EM). Simultaneous measurement of DNA content and immunophenotyping revealed that the cells with higher DNA content (>8 N) constituted less than 5% of the CD41+ fractions until day 14, implying premature apoptosis of MKs before full polyploidization. Nevertheless, EM observation showed not only platelet territories but also newly produced platelets in which granules and microfilaments could be identified. Furthermore, flow cytometry demonstrated that the platelet fraction expressed P-selectin and an activation motif on GPIIb/IIIa recognized by monoclonal antibody PAC-1 upon stimulation with adenosine diphosphate (ADP). In addition, periodic acid-Schiff (PAS)-positive materials and nonspecific esterase activities could be demonstrated. Therefore, it is suggested that platelet production and the accompanying processes, rather than apoptosis only, be hastened during the ex vivo expansion of CB CD34+ cells when using TPO.
Asunto(s)
Antígenos CD34/metabolismo , Sangre Fetal/citología , Hematopoyesis/efectos de los fármacos , Megacariocitos/citología , Megacariocitos/efectos de los fármacos , Trombopoyetina/farmacología , Apoptosis/efectos de los fármacos , Plaquetas/citología , Plaquetas/efectos de los fármacos , Plaquetas/inmunología , Diferenciación Celular/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/inmunología , Humanos , Técnicas In Vitro , Recién Nacido , Megacariocitos/inmunología , Microscopía ElectrónicaRESUMEN
PURPOSE: To report on the use of the laryngeal mask airway (LMA) for elective Cesarean section in 1067 consecutive ASA I-II patients preferring general anesthesia. METHODS: Patients were excluded if they had pharyngeal reflux, a pre-pregnancy body mass index >30, or had a known/predicted difficult airway. Patients were fasted for six hours and given ranitidine/sodium citrate. A rapid sequence induction was performed with thiopentone and suxamethonium. The LMA was inserted by experienced users. Anesthesia was maintained with N(2)O and 50% O(2) and a volatile agent. Cricoid pressure was maintained until delivery, but was relaxed if insertion/ventilation was difficult. Patients were intubated if an effective airway was not obtained within 90 sec, or SpO(2) <94%, or end-tidal CO(2) >45 mmHg. Postdelivery, vecuronium and fentanyl were administered. RESULTS: An effective airway was obtained in 1060 (99%) patients, 1051 (98%) at the first attempt and nine (1%) at the second or third attempt. Air leakage or partial airway obstruction occurred in 22 (21%) patients, and seven (0.7%) patients required intubation. There were no episodes of hypoxia (SpO(2) <90%), aspiration, regurgitation, laryngospasm, bronchospasm or gastric insufflation. Surgical conditions were satisfactory and all APGAR scores were >/=7 after five minutes. CONCLUSION: We conclude that the LMA is effective and probably safe for elective Cesarean section in healthy, selected patients when managed by experienced LMA users.