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This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.
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Fracturas de Cadera , Desnutrición , Humanos , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Evaluación Nutricional , Pronóstico , Desnutrición/complicaciones , Desnutrición/epidemiología , Fracturas de Cadera/etiología , Factores de Riesgo , Evaluación Geriátrica , Estado Nutricional , Estudios RetrospectivosRESUMEN
The interaction of copolymer L61 i.e., (EO)2(PO)32(EO)2 (where EO and PO are ethylene and propylene oxides, respectively) with surfactant SDS (sodium dodecylsulfate) in relation to their self-aggregation, dynamics and microstructures has been physicochemically studied in detail employing the Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), Small-Angle Neutron Scattering (SANS), and Freeze-Fracture Transmission Electron Microscopy (FF-TEM) methods. The NMR self-diffusion study indicated a synergistic interaction between SDS and L61 forming L61-SDS mixed complex aggregates, and deuterium (2H) NMR pointed out the nonspherical nature of these aggregates with increasing [L61]. EPR spectral analysis of the motional parameters of 5-doxyl steraric acid (5-DSA) as a spin probe provided information on the microviscosity of the local environment of the L61-SDS complex aggregates. SANS probed the geometrical aspects of the SDS-L61 assemblies as a function of both [L61] and [SDS]. Progressive evolution of the mixed-aggregate geometries from globular to prolate ellipsoids with axial ratios ranging from 2 to 10 with increasing [L61] was found. Such morphological changes were further corroborated with the results of 2H NMR and FF-TEM measurements. The strategy of the measurements, and data analysis for a concerted conclusion have been presented.
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Trapped magnetic flux in bulk superconductors reduces the quality factor Q in superconducting radio-frequency (SRF) cavities. However, the mechanisms underlying flux trapping and radio-frequency loss are not well understood. Detailed observation of the magnetic distributions is important for understanding such phenomena. Magnetic field mapping is useful for observing the magnetic field distribution around SRF cavities. Measuring the change in the magnetic field around the cavity elucidates the flux trapping behavior. Anisotropic magnetoresistive (AMR) sensors are inexpensive and small devices that can detect magnetic flux density. The magnetic sensitivities of AMR sensors need to be evaluated at liquid helium temperature for the magnetic field mapping of SRF cavities. In this study, a test stand was constructed to calibrate the magnetic sensitivities of AMR sensors in liquid helium, and 110 AMR sensors were tested using this stand. The magnetic sensitivities were evaluated systematically. A solenoid coil was used to control the uniform external magnetic field and to measure the magnetic sensitivity at low temperatures. All AMR sensors exhibited suitable sensitivities to the magnetic field around the SRF cavity. The variation in these sensitivities in all AMR sensors was â¼1%. The AMR sensors were found to have sufficient sensitivity for mapping the magnetic field around the exterior surface of the SRF cavity.
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BACKGROUND: Previous research studies have assessed the relationship between attention to social information and peripheral (e.g., plasma and salivary) oxytocin (OT) levels in typically developing (TD) children and children with autism spectrum disorder (ASD). A relationship between them was observed in TD children, but not in children with ASD. However, this relationship remains unexamined in other age groups. To clarify whether this lack of association is maintained throughout development in individuals with ASD, we aimed to assess the relationship between salivary OT levels and attention to social information in adolescents and adults with and without ASD. METHODS: We recruited male adolescents and adults with ASD (n = 17) and TD participants (n = 24). Using the all-in-one eye-tracking system Gazefinder, we measured the percentage fixation time allocated to social information. We also measured the salivary OT levels and Autism Spectrum Quotient (AQ) of participants. Subsequently, we confirmed group differences and conducted a correlation analysis to investigate the relationships between these three measures. RESULTS: Salivary OT levels did not show any significant difference between the ASD and TD groups and were negatively correlated with the AQ in the whole-group analysis, but not in within-group analysis. Individuals with ASD had significantly lower percentage fixation times than did TD individuals for eye regions in human faces with/without mouth motion, for upright biological motion, and for people regions in the people and geometry movies. The percentage of fixation for geometric shapes in the people and geometry movies was significantly higher in the ASD than in the TD group. In the TD group, salivary OT levels were positively correlated with percentage fixation times for upright biological motion and people and negatively correlated with inverted biological motion and geometry. However, no significant correlations were found in the ASD group. CONCLUSIONS: Our exploratory results suggest that salivary OT levels in adolescents and adults with ASD are less indicative of attention to social stimuli than they are in TD adolescents and adults. It is suggested that their association is slightly weaker in adolescents and adults with ASD and that this attenuated relationship appears to be maintained throughout development.
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Infecciones por Coronavirus , Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Humanos , Radiólogos , SARS-CoV-2RESUMEN
OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.
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Quimioterapia de Mantención , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Puntaje de Propensión , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.
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Neoplasias Laríngeas/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Quimioradioterapia , Femenino , Humanos , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Radiofármacos , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Tasa de Supervivencia , Carga TumoralRESUMEN
Evaluation of bone is of great importance in chronic kidney disease patients, as these patients are at an increased risk for fractures. We treated a hemodialysis patient suffering from hyperparathyroid bone disease with cinacalcet hydrochloride and concurrent administration of maxacalcitol and alfacalcidol for a year. Hyperparathyroid bone disease is characterized by cortical thinning, increased cortical porosity, reduced trabecular bone volume, and increased hypomineralized matrix volume, and there is little information to date about the effects of treatment with cinacalcet hydrochloride on the bone fragility in patients with hyperparathyroid bone disease. In the present study, histological and backscattered electron microscopic evaluation of this combination treatment revealed an excellent improvement of both bone volume and bone morphology. This treatment improved cortical thinning, cortical porosity, and trabecular thinning. Furthermore, the treatment also reduced hypomineralized matrix volume, indicative of improved mineralization by osteocytes. We speculate that the intermittent maxacalcitol administration may have effectively stimulated the vitamin D receptors expressed on osteocytes and osteoblasts, resulting in increased mineralization. Our approach for evaluating the bone in patients with chronic kidney disease by backscattered electron microscopy is novel.
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Conservadores de la Densidad Ósea/uso terapéutico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/tratamiento farmacológico , Hiperparatiroidismo Secundario/complicaciones , Ilion/ultraestructura , Biopsia , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Cinacalcet/uso terapéutico , Humanos , Hidroxicolecalciferoles/uso terapéutico , Hiperparatiroidismo Secundario/patología , Ilion/patología , Microscopía Electrónica , Persona de Mediana EdadRESUMEN
Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.
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Tormentas Ciclónicas , Regulación de la Expresión Génica , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Placenta/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Estrés Psicológico/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Monoaminooxidasa/genética , Monoaminooxidasa/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Estrés Psicológico/metabolismo , Factores de TiempoRESUMEN
We theoretically demonstrate for the first time that a single free electron in circular or spiral motion emits twisted photons carrying well-defined orbital angular momentum along the axis of the electron circulation, in adding to spin angular momentum. We show that, when the electron velocity is relativistic, the radiation field contains harmonic components and the photons of lth harmonic carry lâ total angular momentum for each. This work indicates that twisted photons are naturally emitted by free electrons and are more ubiquitous in laboratories and in nature than ever thought.
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BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.
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Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Hiperuricemia/epidemiología , Hiperuricemia/etiología , Trasplante de Riñón/efectos adversos , Adulto , Alopurinol/uso terapéutico , Benzbromarona/efectos adversos , Febuxostat/uso terapéutico , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Ribonucleósidos/efectos adversos , Ribonucleósidos/uso terapéutico , Receptores de Trasplantes , Ácido Úrico/sangre , Uricosúricos/efectos adversosRESUMEN
BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.
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Modelos Animales de Enfermedad , Tránsito Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/fisiología , Ileus/tratamiento farmacológico , Canal Catiónico TRPA1/agonistas , Canal Catiónico TRPA1/fisiología , Acroleína/análogos & derivados , Acroleína/farmacología , Acroleína/uso terapéutico , Amidas/farmacología , Amidas/uso terapéutico , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ileus/fisiopatología , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Naftoquinonas/farmacología , Naftoquinonas/uso terapéutico , Técnicas de Cultivo de ÓrganosRESUMEN
OBJECTIVE: The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. METHODS: We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 µmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukey's honest significant difference (HSD) test]. RESULTS: In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. CONCLUSION: Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. ADVANCES IN KNOWLEDGE: USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.
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Aorta Abdominal/patología , Aterosclerosis/patología , Hiperlipidemias/patología , Angiografía por Resonancia Magnética/métodos , Placa Aterosclerótica/patología , Animales , Aorta Abdominal/metabolismo , Aterosclerosis/diagnóstico , Aterosclerosis/metabolismo , Medios de Contraste , Dextranos , Modelos Animales de Enfermedad , Hiperlipidemias/diagnóstico , Hiperlipidemias/metabolismo , Macrófagos/metabolismo , Nanopartículas de Magnetita , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/metabolismo , ConejosRESUMEN
We have developed a practical method for determining an excellent initial arrangement of magnetic arrays for a pure-magnet Halbach-type undulator. In this method, the longitudinal magnetic field distribution of each magnet is measured using a moving Hall probe system along the beam axis with a high positional resolution. The initial arrangement of magnetic arrays is optimized and selected by analyzing the superposition of all distribution data in order to achieve adequate spectral quality for the undulator. We applied this method to two elliptically polarizing undulators (EPUs), called U#16-2 and U#02-2, at the Photon Factory storage ring (PF ring) in the High Energy Accelerator Research Organization (KEK). The measured field distribution of the undulator was demonstrated to be excellent for the initial arrangement of the magnet array, and this method saved a great deal of effort in adjusting the magnetic fields of EPUs.
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This article provides an overview of phase-contrast and time-spatial labeling inversion pulse MR imaging techniques to assess CSF movement in the CNS under normal and pathophysiologic situations. Phase-contrast can quantitatively measure stroke volume in selected regions, notably the aqueduct of Sylvius, synchronized to the heartbeat. Judicious fine-tuning of the technique is needed to achieve maximal temporal resolution, and it has limited visualization of CSF motion in many CNS regions. Phase-contrast is frequently used to evaluate those patients with suspected normal pressure hydrocephalus and a Chiari I malformation. Correlation with successful treatment outcome has been problematic. Time-spatial labeling inversion pulse, with a high signal-to-noise ratio, assesses linear and turbulent motion of CSF anywhere in the CNS. Time-spatial labeling inversion pulse can qualitatively visualize whether CSF flows between 2 compartments and determine whether there is flow through the aqueduct of Sylvius or a new surgically created stoma. Cine images reveal CSF linear and turbulent flow patterns.
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Malformación de Arnold-Chiari/diagnóstico , Hidrocéfalo Normotenso/diagnóstico , Imagen por Resonancia Magnética/métodos , Malformación de Arnold-Chiari/fisiopatología , Acueducto del Mesencéfalo/fisiopatología , Humanos , Hidrocefalia/fisiopatología , Hidrocéfalo Normotenso/fisiopatología , Reología/métodos , Procesamiento de Señales Asistido por Computador , Relación Señal-Ruido , Análisis Espacio-TemporalRESUMEN
Previous studies have suggested that the human leukocyte antigen (HLA) is involved in the etiology of Crohn's disease (CD); however, few reports are available on the association between HLA class I antigens and CD in Japan. In this study, we performed association analysis of HLA class I antigens in CD using 208 Japanese patients and 384 healthy controls. We identified novel positive associations between CD and HLA-A*02:01 (odds ratio (OR)=1.64, P=0.016) and HLA-A*02:07 (OR=2.31, P=0.0067) and confirmed previously reported positive associations between CD and HLA-Cw*14:02 (OR=2.18, P=0.0021) and HLA-B*51:01 (OR=1.70, P=0.033). We also identified novel negative associations between CD and HLA-A*24:02 (OR=0.60, P=0.0047) and HLA-B*07:02 (OR=0.38, P=0.0041). Although the associations were not significant after full Bonferroni correction, we suggested that HLA class I genes have dual functions, susceptibility and resistance in controlling the development of CD.
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Enfermedad de Crohn/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Genes MHC Clase I , Humanos , JapónRESUMEN
UNLABELLED: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. INTRODUCTION: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. METHODS: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥ 300 pg/mL). RESULTS: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex (t = 3.24, P = 0.01; 95% confidence interval [CI] 11.78 to 50.43) and phosphate level (t = 2.13, P = 0.04; 95% CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level (t = 1.90, P = 0.06, 95% CI -1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1%), B (88.0%), C (85.2%), and D (90.5%). CONCLUSION: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment.
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Proteínas Morfogenéticas Óseas/sangre , Hormona Paratiroidea/deficiencia , Diálisis Renal , Vitamina D/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Suplementos Dietéticos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Marcadores Genéticos , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fosfatos/sangre , Adulto JovenRESUMEN
Patients with high FLT3 internal tandem duplication allelic ratios (FLT3/ITD-ARs) have a poor prognosis. Single-nucleotide polymorphism/comparative genomic hybridization, single-cell PCR and colony-forming assays were used to evaluate genotypic evolution of high FLT3/ITD-ARs in 85 acute myeloid leukemia (AML) patients. Microarrays were used to examine molecular pathways disrupted in leukemic blasts with high FLT3/ITD-ARs. Copy-neutral loss of heterozygosity (CN-LOH) was identified at the FLT3 locus in diagnostic samples with high FLT3/ITD-ARs (N=11), but not in samples with low FLT3/ITD-ARs (N=24), FLT3-activating loop mutations (N=11) or wild-type FLT3 (N=39). Single-cell assays showed that homozygous FLT3/ITD genotype was present in subsets of leukemic blasts at diagnosis but became the dominant clone at relapse. Less differentiated CD34(+)/CD33(-) progenitor colonies were heterozygous for FLT3/ITD, whereas more differentiated CD34(+)/CD33(+) progenitor colonies were homozygous for FLT3/ITD. Expression profiling revealed that samples harboring high FLT3/ITD-ARs aberrantly expressed genes within the recombination/DNA repair pathway. Thus, the development of CN-LOH at the FLT3 locus, which results in high FLT3/ITD-ARs, likely represents a late genomic event that occurs after the acquisition of the FLT3/ITD. Although the etiology underlying the development of CN-LOH remains to be clarified, the disruption in recombination/DNA repair pathway, which is present before the development of LOH, may have a role.
Asunto(s)
Leucemia Mieloide Aguda/genética , Pérdida de Heterocigocidad , Tirosina Quinasa 3 Similar a fms/genética , Alelos , Niño , Genotipo , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/patología , Recurrencia Local de Neoplasia/enzimología , Recurrencia Local de Neoplasia/genética , Polimorfismo de Nucleótido Simple , Pronóstico , Secuencias Repetidas en TándemRESUMEN
BACKGROUND: Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT: A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography-CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. CONCLUSIONS: It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%-0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.