RESUMEN
Ischemic stroke, which results in loss of neurological function, initiates a complex cascade of pathological events in the brain, largely driven by excitotoxic Ca2+ influx in neurons. This leads to cortical spreading depolarization, which induces expression of genes involved in both neuronal death and survival; yet, the functions of these genes remain poorly understood. Here, we profiled gene expression changes that are common to ischemia (modeled by middle cerebral artery occlusion [MCAO]) and to experience-dependent activation (modeled by exposure to an enriched environment [EE]), which also induces Ca2+ transients that trigger transcriptional programs. We found that the activity-dependent transcription factor Npas4 was up-regulated under MCAO and EE conditions and that transient activation of cortical neurons in the healthy brain by the EE decreased cell death after stroke. Furthermore, both MCAO in vivo and oxygen-glucose deprivation in vitro revealed that Npas4 is necessary and sufficient for neuroprotection. We also found that this protection involves the inhibition of L-type voltage-gated Ca2+ channels (VGCCs). Next, our systematic search for Npas4-downstream genes identified Gem, which encodes a Ras-related small GTPase that mediates neuroprotective effects of Npas4. Gem suppresses the membrane localization of L-type VGCCs to inhibit excess Ca2+ influx, thereby protecting neurons from excitotoxic death after in vitro and in vivo ischemia. Collectively, our findings indicate that Gem expression via Npas4 is necessary and sufficient to promote neuroprotection in the injured brain. Importantly, Gem is also induced in human cerebral organoids cultured under an ischemic condition, revealing Gem as a new target for drug discovery.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Accidente Cerebrovascular Isquémico/fisiopatología , Proteínas de Unión al GTP Monoméricas/metabolismo , Neuronas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Muerte Celular , Células HEK293 , Humanos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/mortalidad , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Unión al GTP Monoméricas/genética , Neuronas/patología , OrganoidesRESUMEN
AIMS: While bowel preparation for colonoscopy is the key to successful examination, taking laxatives and showing stools to others causes both physical and mental distress to the patient. Thus, an alternative method to evaluation bowel preparation is necessary. In the current study, we studied the colonic fecal retention by ultrasonography (US) and examined the US finding which reflected completion of BP. MATERIAL AND METHODS: The subjects were outpatients who underwent colonoscopy. This report summarizes the ultrasonographic images of patients who underwent multiple US examinations for all five sites of the colon just before, during, and immediately after bowel preparation. According to the standard protocol, the patients took 2 L of polyethylene glycol-ascorbic acid as a laxative, which was discontinued when the nurse visually judged the stool to be clear. RESULTS: Seven patients in their 50s-80s, none of whom were unable to complete a colonoscopy due to residual feces were included in study. Following bowel preparation, the US images showed anechoic areas with haustration in four or all five areas of the colon. Three of the seven patients received low-dose laxatives (1.1-1.2 L); all three had watery stools in three or more colon areas and none of them were constipated at the time of taking 1 L of laxatives. CONCLUSIONS: Completion of bowel preparation can be assessed by the observation of anechoic areas with haustration in multiple colonic sites by ultrasonography.
Asunto(s)
Colonoscopía , Heces , Colon , Humanos , Laxativos , PolietilenglicolesRESUMEN
PURPOSE: We performed lumbar spinal magnetic resonance imaging of three-dimensional (3D) dual echo volumetric isotropic turbo spin echo acquisition (DE-VISTA) and constructed DE-VISTA additional fusion images (DE-VISTA-AFI), which is the addition of DE-VISTA proton density-weighted images (DE-VISTA-PDWI) to DE-VISTA T2-weighted images (DE-VISTA-T2WI). The aim of this study was to clarify whether DE-VISTA-AFI was able to clearly delineate spinal nerve roots. METHODS: A total of 677 patients underwent lumbar MR imaging, and the signal ratio (SR) between cerebrospinal fluid and nerve roots inside the dural sac and the SR between fat and nerve roots outside the dural sac were estimated using DE-VISTA-AFI, DE-VISTA-PDWI, DE-VISTA-T2WI, and 2D-T2WI. RESULTS: The SR between cerebrospinal fluid and nerve roots inside the dural sac on DE-VISTA-AFI was higher than that on DE-VISTA-PDWI (p < 0.0001) and on 2D T2WI (p < 0.0001). The SR between the fat tissue and nerve roots outside the dural sac on DE-VISTA-AFI was higher than that on DE-VISTA-PDWI (p < 0.0001) and 2D T2WI (p < 0.0001). CONCLUSION: DE-VISTA-AFI could clearly delineate the entire length of the lumbar nerve roots that run from the cauda equina in the spinal fluid through to the fat in the lateral recess, intervertebral foramen, and outside the intervertebral foramen.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/inervación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/inervación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: It has been reported that recombinant human soluble thrombomodulin (rhsTM) has a high-mobility group box (HMGB)1 inhibitory effect. Some investigators reported that HMGB1 is associated with ischemic stroke. However, there have been no previous studies to determine whether rhsTM can ameliorate cerebral ischemic injury through its HMGB1 inhibitory mechanism in ischemic stroke. We investigated the effects of rhsTM on cerebral ischemic injury in a 4-h middle cerebral artery occlusion (MCAO) murine model. METHODS: rhsTM (1 or 5mg/kg, i.v.) was administered immediately after 4-h MCAO. Infarct volume, motor coordination, plasma HMGB1 level, and hemorrhage volume were evaluated 24h after 4-h MCAO. RESULTS: The infarct volume (P<0.05) was reduced by rhsTM in mice subjected to 4-h MCAO in a dose-dependent manner. Moreover, rhsTM (5mg/kg) significantly improved motor coordination determined by the rotarod test (P<0.05), and significantly decreased plasma HMGB1 level compared with vehicle-treated controls (P<0.001). In addition, there was no difference in hemorrhage volume between vehicle-treated controls and the rhsTM treatment group. CONCLUSIONS: This represents the first report that rhsTM ameliorates cerebral ischemic injury through an HMGB1 inhibitory mechanism without hemorrhagic complications in mice. Taken together, these observations indicate a palliative effect of rhsTM and suggest new therapeutic possibilities for treatment of ischemic stroke via inhibition of HMGB1.
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Proteína HMGB1/sangre , Hemorragia/etiología , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/tratamiento farmacológico , Trombomodulina/uso terapéutico , Análisis de Varianza , Animales , Infarto Cerebral/etiología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Examen Neurológico , Proteínas Recombinantes/farmacologíaRESUMEN
The filament perforation model (FPM) in mice is becoming increasingly popular to elucidate the molecular pathogenesis of neuronal injury after subarachnoid hemorrhage (SAH). We evaluated brain MRI in a mouse FPM. A total of 28 male C57Bl/6J mice were used. Seventeen animals underwent SAH induction by FPM. In two animals, transient middle cerebral artery occlusion (MCAo) was induced. Nine mice served as controls. T1-weighted images (T1WI), T2-weighted images (T2WI), T2(∗)-weighted images (T2*WI) and apparent diffusion coefficient maps were acquired at day 0 and at various time points following SAH (range: day 1-6 after SAH). Cerebral blood flow (CBF) analysis by (14)C-iodoamphetamine ((14)C-IMP) autoradiography was conducted in nine animals. Hemorrhage could be best confirmed using T2*WI. The degree of hemorrhage varied. All animals evaluated for ⩾2days were hydrocephalic, which was best seen on T2WI. T2-hyperintensity of the corpus callosum and external capsule, indicating white matter (WM) injury, was present after SAH. Ventricle and WM injury volumes were statistically significantly higher at day 3 compared to day 0. Territorial ischemia was detectable in MCAo but not in SAH. Markedly hypointense cortical veins were visible in the hyperacute and delayed phase after SAH on T2*WI. The (14)C-IMP analysis indicated decreased CBF after SAH. MRI is feasible and useful in evaluating pathophysiological changes over time. T2*WI seems best for SAH detection and grading. The chronological change of hydrocephalus and WM injury could be analyzed. T2*WI illustrated specific signal changes of cortical veins, possibly caused by increased oxygen extraction fraction due to decreased CBF.
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Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Animales , Angiografía Cerebral , Infarto de la Arteria Cerebral Media/patología , Angiografía por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Hemorragia Subaracnoidea/patologíaRESUMEN
OBJECTIVE: To evaluate the relationship between fiber bundle direction and changes in diffusion kurtosis, we evaluated the apparent diffusion kurtosis coefficients (AKCs) that were perpendicular to and parallel to the principal diffusion tensor eigenvector. MATERIALS AND METHODS: Adult male Wistar rats were subjected to 30 or 60 minutes of middle cerebral artery occlusion and imaged with a 7T Magnetic Resonance Imager System (Varian MRI System 7T/210: Agilent Technologies, CA). Diffusion kurtosis images were obtained before middle cerebral artery (MCA) reperfusion and 3, 6, and 24 hours after reperfusion to generate the apparent diffusion coefficient (ADC), fractional anisotropy (FA), mean apparent diffusion kurtosis coefficient (mAKC), AKC axial to the eigenvector (axAKC), and AKC radial to the eigenvector (radAKC) images. The time course of the region/normal ratio was evaluated for the above parameters in the caudoputamen and white matter. RESULTS: Relative FA and relative ADC values decreased 3 hours after MCA reperfusion and remained decreased until 24 hours. Relative mAKC, axAKC, and radAKC values were increased 3 hours after MCA reperfusion, peaked after 6 hours, and slightly decreased after 24 hours. In the white matter, axAKC showed larger changes than radAKC. CONCLUSION: The time course of the diffusion kurtosis value showed earlier pseudonormalization than the ADC value of the lesions. For white matter lesions, the increase in axAKC was larger than that in radAKC, suggesting that the tissue changes after infarction mainly produce reduced diffusivity along the fibers and lead to increased inhomogeneity of the diffusion.
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Infarto Cerebral/etiología , Imagen de Difusión por Resonancia Magnética , Infarto de la Arteria Cerebral Media/complicaciones , Análisis de Varianza , Animales , Anisotropía , Infarto Cerebral/diagnóstico por imagen , Modelos Animales de Enfermedad , Procesamiento de Imagen Asistido por Computador , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
We report the case of a 46-year-old female who presented with a category IV pressure ulcer (PU) in the sacral region. Undermining of the PU was assessed with the aid of two-dimensional and three-dimensional ultrasound (3D-US).3D-US clearly visualized the wound in three directions and allowed determination of its volume. Our results show that volumetric analysis carried out with 3D-US enables the evaluation of wound morphology and thus better treatment of patients with PUs. The technique is simple and can be used routinely in daily wound management to assess the volume of the undermined wound.
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Imagenología Tridimensional , Región Lumbosacra/diagnóstico por imagen , Úlcera por Presión/diagnóstico por imagen , Femenino , Humanos , Región Lumbosacra/patología , Persona de Mediana Edad , Úlcera por Presión/patología , UltrasonografíaRESUMEN
Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke.
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Proteínas ADAM/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Proteína ADAMTS13 , Animales , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/etiología , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/etiología , Circulación Cerebrovascular/efectos de los fármacos , Modelos Animales de Enfermedad , Proteína HMGB1/sangre , Flujometría por Láser-Doppler , Masculino , Ratones , Ratones Endogámicos , Examen Neurológico , Factores de Tiempo , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND: Medial longitudinal fasciculus (MLF) syndrome refers to a gaze disorder characterized by impaired adduction on the ipsilateral side to the injured MLF, with dissociated nystagmus of the contralateral abducting eye. The most common cause of the MLF syndrome is ischemic stroke. However, acute ischemic change in the MLF may be undetectable even on diffusion-weighted magnetic resonance imaging (DW-MRI) partly because of its small size and specific brainstem location. CASE REPORT: Herein, we present the first reported case of MLF syndrome in which, compared with the standard-b-value DWI, a higher b-value DWI revealed more clearly a small infarction in the dorsal pons in the acute stage. CONCLUSIONS: We suggest that high-b-value DWI can be a useful diagnostic method for patients with MLF syndrome caused by possible brainstem ischemia and thus supportive for deciding the optimal treatment for such patients.
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Isquemia Encefálica/complicaciones , Tronco Encefálico/patología , Nistagmo Patológico/etiología , Isquemia Encefálica/patología , Imagen de Difusión por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Nistagmo Patológico/patologíaRESUMEN
We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS.
RESUMEN
Experiments using genetically engineered mice are regarded as indispensable to gaining a better understanding of the molecular pathophysiology in neuronal injury after subarachnoid hemorrhage (SAH). Therefore, mouse SAH models are becoming increasingly important. The circle of Willis perforation (cWp) model is the most frequently used mouse SAH model. We report and discuss the technical surgical approach, results, and difficulties associated with the cWp model, with reference to the existing literature. Our results largely confirmed previously published results. This model may be the first choice at present, because important pathologies can be reproduced in this model and most findings in the literature are based on it.
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Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Hemorragia Subaracnoidea/fisiopatología , Vasoespasmo Intracraneal/fisiopatología , Animales , Ingeniería Genética/métodos , Ratones Transgénicos , Procedimientos Neuroquirúrgicos/métodos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/cirugíaRESUMEN
OBJECTIVE: Mouse subarachnoid hemorrhage (SAH) models are becoming increasingly important. We aimed to report and discuss the detailed technical-surgical approach and difficulties associated with the circle of Willis perforation (cWp) model, with reference to the existing literature. METHODS: First, the cWp model was reproduced using ddY mice following scarification at 0 h, Days 1, 2, and 3 after SAH. Second, C57BL/6 mice were subjected to SAH with histological examination on Days 1, 2, and 3. Sham-operated mice were sacrificed on Day 2. Neurological performance, amount of subarachnoid blood, cerebral vasospasm (CVS), and neuronal injury were assessed. Relevant articles found in the MEDLINE database were reviewed. RESULTS: Induction of SAH was successfully reproduced. The volume of subarachnoid blood decreased with time due to resorption. Neurological performance was worse in SAH compared with sham. Signs of CVS could be confirmed on Days 2 and 3, but not Day 1. The cumulative number of microthrombi was significantly higher on Days 2 and 3, but not Day 1. Apoptotic and degenerative neurons were found in the cortex and hippocampal area. Our review of the literature revealed the cWp model to be the most frequently used. The present findings largely confirmed previously published results. However, detailed technical-surgical description and its discussion were sparse, which we provide here. CONCLUSIONS: The current study provides additional useful information characterizing the cWp model. This model may be of first choice at present, as important pathologies can be reproduced and most findings in the literature are based on it.
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Círculo Arterial Cerebral/cirugía , Modelos Animales de Enfermedad , Procedimientos Neuroquirúrgicos/métodos , Hemorragia Subaracnoidea/cirugía , Animales , Círculo Arterial Cerebral/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Hemorragia Subaracnoidea/patologíaRESUMEN
UNLABELLED: The burn severity depends on the wound depth and area affected. Hitherto burn depth has been judged mainly by visual observation, although concerns have been raised about its validity. The regional tissue blood flow (rTBF) measured by laser Doppler imaging (LDI) in damaged tissue correlates with the depth. However, very few reports are available on the significance of the regional tissue oxygen saturation (rSO2) as an indicator of burn depth. We investigated whether rSO2 by Near-infrared spectroscopy (NIRS) in burn injuries correlates with rTBF by LDI, which would facilitate quantification of the severity of the tissue damage. METHODS: We measured rTBF and rSO2 in 50 lesions from 14 patients of burn injury within 24 hours after injury. The correlation between rTBF and rSO2 was evaluated by Spearman rank correlation analysis. RESULTS: The rSO2 (%; range, 52-82) by NIRS and the rTBF (perfusion unit; range, 61-704) by LDI in burn lesions were positively correlated (r=0.755, p<0.001). This statistically positive correlation still remained significant (r=0.678, p<0.001) after the rSO2 values were standardized. CONCLUSION: This study suggests that NIRS determination of rSO2 in burn injuries shows promise as a reliable and quick method to estimate the depth of burn lesion.
RESUMEN
As a sequel of brain ischemia, selective neuronal loss (SNL)-as opposed to pannecrosis (i.e. infarction)-is attracting growing interest, particularly because it is now detectable in vivo. In acute stroke, SNL may affect the salvaged penumbra and hamper functional recovery following reperfusion. Rodent occlusion models can generate SNL predominantly in the striatum or cortex, showing that it can affect behavior for weeks despite normal magnetic resonance imaging. In humans, SNL in the salvaged penumbra has been documented in vivo mainly using positron emission tomography and (11)C-flumazenil, a neuronal tracer validated against immunohistochemistry in rodent stroke models. Cortical SNL has also been documented using this approach in chronic carotid disease in association with misery perfusion and behavioral deficits, suggesting that it can result from chronic or unstable hemodynamic compromise. Given these consequences, SNL may constitute a novel therapeutic target. Selective neuronal loss may also develop at sites remote from infarcts, representing secondary 'exofocal' phenomena akin to degeneration, potentially related to poststroke behavioral or mood impairments again amenable to therapy. Further work should aim to better characterize the time course, behavioral consequences-including the impact on neurological recovery and contribution to vascular cognitive impairment-association with possible causal processes such as microglial activation, and preventability of SNL.
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Isquemia Encefálica/patología , Neuronas/patología , Accidente Cerebrovascular/patología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Isquemia Encefálica/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/patología , Muerte Celular , Imagen de Difusión por Resonancia Magnética , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/patología , Tomografía de Emisión de Positrones , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Susceptibility-weighted imaging (SWI) has recently attracted attention for its ability to investigate acute stroke pathophysiology. SWI detects an increased ratio of deoxyhemoglobin to oxyhemoglobin in cerebral venous compartments, which can illustrate cerebral misery perfusion with a compensatory increase of oxygen extraction fraction in the hypoperfused brain. In this study we make the first case report of blunt cervical trauma leading to a stroke, demonstrating the disparity between diffusion-weighted imaging (DWI) and SWI changes, or DWI-SWI mismatch, in the acute ischemic brain. The area of mismatch between a smaller DWI cytotoxic edema and a larger SWI misery perfusion in our patient matured into a complete infarction with time. The DWI-SWI mismatch may signify the presence of an ischemic penumbra, and provide information about viability of the brain tissue at risk of potential infarction if without early reperfusion.
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Isquemia Encefálica/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/patología , Accidentes de Trabajo , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/cirugía , Isquemia Encefálica/cirugía , Traumatismos de las Arterias Carótidas/complicaciones , Traumatismos de las Arterias Carótidas/diagnóstico por imagen , Traumatismos de las Arterias Carótidas/cirugía , Disección de la Arteria Carótida Interna/diagnóstico por imagen , Disección de la Arteria Carótida Interna/etiología , Disección de la Arteria Carótida Interna/cirugía , Circulación Cerebrovascular/fisiología , Humanos , Masculino , Persona de Mediana Edad , Traumatismos del Cuello/diagnóstico por imagen , Traumatismos del Cuello/cirugía , Radiografía , Accidente Cerebrovascular/cirugíaRESUMEN
BACKGROUND: The role and impact of systemic inflammatory response after aneurysmal subarachnoid hemorrhage remain to be elucidated. OBJECTIVE: To assess the time course and correlation of systemic inflammatory parameters with outcome and the occurrence of delayed ischemic neurological deficits (DINDs) after subarachnoid hemorrhage. METHODS: Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow outcome scale; the secondary end point was the occurrence of DINDs. RESULTS: During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow outcome scale score, 1-3). After adjustment for confounding factors, elevated IL-6 and leukocyte counts remained significant risk factors for unfavorable outcome. The odds ratio for log IL-6 was 4.07 (95% confidence interval, 1.18 to 14.03; P = .03) and for leukocyte counts was 1.24 (95% confidence interval, 1.06-1.46, P = .008). The analysis of the time course established that IL-6 was the only significantly elevated parameter in the early phase in patients with unfavorable outcome. Higher IL-6 levels in the early phase (days 3-7) were associated with the occurrence of DINDs. The adjusted odds ratio for log IL-6 was 4.03 (95% confidence interval, 1.21-13.40; P = .02). CONCLUSION: Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.
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Inflamación/patología , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patología , Adulto , Anciano , Biomarcadores , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Péptido Relacionado con Gen de Calcitonina , Angiografía Cerebral , Intervalos de Confianza , Determinación de Punto Final , Femenino , Escala de Consecuencias de Glasgow , Humanos , Hipotermia Inducida , Inflamación/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Precursores de Proteínas/sangre , Curva ROC , Tamaño de la Muestra , Hemorragia Subaracnoidea/terapia , Resultado del TratamientoRESUMEN
The prognosis for pancreatic cancer with distant metastasis is not good. The case reported here concerns a pancreatic body cancer with multiple liver metastases for which multidisciplinary therapy of S-1+gemcitabine(GEM)therapy, surgery, and radiofrequency ablation proved to be effective, resulting in complete remission. The patient was a 77-year-old female. She was asymptomatic and diagnosed with pancreatic body cancer with multiple liver metastasis at the end of December 2008 by ultrasonography. After careful examination, GEM 1, 200mg/body was administered on days 1 and 15, and S-1 was administered orally at 80mg/day for two weeks, followed by two weeks of rest. By the end of the 15th course, the size of the tumor had reduced from 26. 5mm to 14. 4mm, and all but one of the liver lesions disappeared; the remaining one lesion was measured as 14. 5mm by ultrasonography. We performed pancreas body and tail resection and radiofrequency therapy for the remaining single liver metastasis. After operation, GEM was administered once a month for 4 months. S-1 was not administered, but a new lesion was revealed at the S8 area by ultrasonography. We restarted S-1+GEM therapy and in 5 months the new lesion disappeared from image examinations. She is alive and in complete remission 16 months after the operation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Combinación de Medicamentos , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Ácido Oxónico/administración & dosificación , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Inducción de Remisión , Tegafur/administración & dosificación , GemcitabinaRESUMEN
Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia-reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia-reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia-reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia-reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.
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Encéfalo/metabolismo , Eliminación de Gen , Proteína HMGB1/sangre , Metaloendopeptidasas/genética , Daño por Reperfusión/genética , Proteína ADAMTS13 , Animales , Encéfalo/patología , Circulación Cerebrovascular/fisiología , Inmunohistoquímica , Inflamación/metabolismo , Inflamación/patología , Masculino , Metaloendopeptidasas/metabolismo , Ratones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
Patients with spontaneous non-aneurysmal subarachnoid hemorrhage (non-aSAH) are considered to have a benign illness in contrast to patients with aSAH. The occurrence of the systemic inflammatory response syndrome has been linked to worse outcomes in patients with aSAH. We analyzed systemic interleukin (IL)-6, a proinflammatory cytokine, to determine whether its concentration differs between patients with non-aSAH and those with aSAH, reflecting the more benign illness. Daily systemic IL-6 levels were measured in the acute phase in 11 patients with non-aneurysmal perimesencephalic SAH (pmSAH), with bleeding strictly located around the midbrain, and in nine patients with non-aneurysmal non-perimesencephalic (non-pmSAH), with hemorrhage extending into adjacent cisterns (group 1). IL-6 levels were compared with those from patients suffering from aSAH with cerebral vasospasm (CVS) (group 2) and without CVS (group 3). The mean IL-6 level (±standard error of the mean) was significantly lower in group 1 compared to group 2 (9.9±1.9 vs. 29.1±6.7 pg/mL, p=0.018). The difference in mean IL-6 level between group 1 and 3 fell short of significance (9.9±1.9 vs. 14.9±1.1 pg/mL, p=0.073). Patients in group 1 had a significantly better outcome (Glasgow Outcome Scale score 4-5) compared to group 2 (p<0.001) and a trend towards better outcome compared to group 3 (p=0.102). A subgroup analysis revealed a higher mean IL-6 concentration in patients with non-pmSAH compared to patients with pm-SAH (p=0.001). We concluded that systemic IL-6 concentration reflects the severity of the inflammatory stress response and course of the illness. The more benign illness and good prognosis of patients with pmSAH or non-pmSAH in contrast to patients with aSAH is reflected by the lower concentrations of IL-6.