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AIM: To modify the antibody prevalence in epilepsy (APE) score of children with suspected autoimmune central nervous system disease with seizures. METHODS: We retrospectively analysed the cerebrospinal fluid of 157 children (aged 0-18 years) with suspected autoimmune central nervous system disease for antineuronal antibodies in our laboratory from 2016 to 2023. Participants were randomly divided into the development cohort (n = 79, 35 females; median 7 years, SD 4 years 7 months, range 4-11 years) and validation cohort (n = 78, 28 females; median 7 years, SD 4 years 5 months, range 4-12 years). A paediatric antibody prevalence in seizure (PAPS) score was created for one cohort and evaluated in the other. Seven variables were selected through univariate and multivariate analysis to create a PAPS score. RESULTS: One hundred and fifty-seven children who fulfilled the inclusion criteria were enrolled; 49 tested positive for antineuronal antibodies. The sensitivity and specificity of an APE score of 4 and greater were 92% and 22.2% respectively; the sensitivity and specificity of a PAPS score of 2.5 and greater were 83.3% and 77.8% respectively. The area under the curve was 0.832 (95% confidence interval = 0.743-0.921), which was significantly better than that for the APE score (p < 0.001). INTERPRETATION: The APE score had high sensitivity but low specificity in children. The PAPS score may be useful for determining the need for antineuronal antibody testing.
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AIM: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES. METHOD: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes. RESULTS: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed. INTERPRETATION: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.
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BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1ß, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1ß, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.
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Encefalopatías , Convulsiones Febriles , Niño , Humanos , Citocinas , Interleucina-17 , Interferón gamma , Interleucina-4 , Estudios Retrospectivos , Interleucina-5RESUMEN
The NLRP3 inflammasome is a molecular complex that translates signals from pathogens and tissue damage into inflammatory responses, and plays crucial roles in numerous neurological diseases. Activation of the NLRP3 inflammasome leads to caspase-1 dependent cleavage of pro-IL-1ß to form mature IL-1ß. By acting on the P2X7 purinergic receptor, extracellular ATP is one of the major stimuli that activates the NLRP3 inflammasome. Although microglia express multiple purinergic receptors, their roles in inflammasome-mediated inflammation are largely unknown. We studied the role of the P2Y12 receptor, a metabotropic P2Y receptor enriched in microglia, on inflammation in vitro. Inhibition of the microglial P2Y12 receptor by PSB0739 or siRNA knockdown suppressed IL-1ß release. P2Y12 receptor-deficient microglia displayed markedly attenuated IL-1ß mRNA expression and release. P2Y12 receptor blockade also suppressed IL-6 production. Both IL-1ß and IL-6 responses were augmented by extracellular ADP or ADP-ßS and were abrogated by PSB0739. Mechanistically, ADP-ßS potentiated NF-κB activation. In addition, ADP altered mitochondrial membrane potential in combination with ATP and increased the number of caspase-1 positive cells through the P2Y12 receptor. These results elucidate a novel inflammatory mechanism by which extracellular ADP acts on the P2Y12 receptor to activate NF-κB and the NLRP3 inflammasome to enhance microglial inflammation.
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Adenosina Difosfato/metabolismo , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Animales , Caspasa 1/metabolismo , Línea Celular , Citocinas/metabolismo , Regulación de la Expresión Génica/fisiología , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Ratones , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.
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Biomarcadores/sangre , Trastornos de la Coagulación Sanguínea/sangre , Encefalopatías/sangre , Quimiocinas/sangre , Citocinas/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Choque Hemorrágico/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/terapia , Encefalopatías/diagnóstico , Encefalopatías/terapia , Quimiocina CCL2/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/terapia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: While accumulating evidence suggests a relation between the severity of alcohol dependence and the risk of its recurrence, the impact of dependence severity on the course of the disorder has not been carefully evaluated. The present study examined the impact of several severity indices of alcohol dependence on the drinking course after inpatient treatment. METHODS: This prospective study was conducted over a 12-month period following alcohol treatment at a specialized hospital. A total of 712 consecutively admitted alcohol-dependent patients were targeted for enrollment at the time of their hospitalization, with 637 patients registered and followed. The characteristics and severity of the subjects were assessed using multiple methods at admission, with their course after discharge followed continuously using mailed questionnaires that queried them regarding their drinking behavior. RESULTS: Greater severity of dependence, assessed using the number of ICD-10 diagnostic criteria met, was associated with a lower rate of abstinence during the study period (p = 0.035). The rate of abstinence also decreased significantly as the baseline blood gamma-glutamyl transferase value and Alcohol Dependence Scale (ADS) score increased (p = 0.031 and p = 0.0002, respectively). In multivariate Cox proportional hazards analyses, the group with the most severe ADS scores had a significantly greater risk of relapse to drinking than the group with the least severe scores (HR = 2.67, p = 0.001). Dependence severity also associated with the drinking pattern; participants in both the controlled drinking group and the abstinence group had lower ADS scores at admission and a later age at first drinking (p = 0.001 and p < 0.001, respectively) than those with poorer drinking outcomes. CONCLUSIONS: The present study showed that more severe alcohol dependence predicts a poorer course after alcohol treatment, as reflected by findings on multiple measures. These results suggest that assessing the dependence severity at the outset of treatment could be useful both in predicting treatment outcome and targeting interventions to alcohol-dependent individuals who need additional support in their recovery.
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Alcoholismo/terapia , Aceptación de la Atención de Salud/psicología , Índice de Severidad de la Enfermedad , Templanza/psicología , Adaptación Psicológica , Adulto , Alcoholismo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Entrevista Motivacional/métodos , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
Ovarian mature cystic teratomas comprise tissues derived from all three germ layers. In rare cases, malignant tumors arise from ovarian mature cystic teratoma. A variety of tumors can arise from mature cystic teratoma, among which primary malignant melanoma (MM), for which no molecular analyses such as genomic sequencing have been reported to date, is exceedingly rare, thereby limiting possible therapeutic options using precision medicine. We used targeted gene sequencing to analyze the status of 160 cancer-related genes in a patient with MM arising from an ovarian mature cystic teratoma (MM-MCT). KRAS amplification and homozygous deletion in PTEN and RB1 were detected in tumor samples collected from the patient. No KRAS amplification has been previously reported in cutaneous MM, indicating that the carcinogenesis of MM-MCT differs from that of primary cutaneous melanomas. A better understanding of the underlying genetic mechanisms will help clarify the carcinogenesis of MM-MCT. In turn, this will enable treatment with novel targeting agents as well as the initial exploration of gene-based precision oncological therapies, which aim to improve treatment outcomes for patients with this disease.
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Genes Relacionados con las Neoplasias , Melanoma/genética , Mutación , Neoplasias Ováricas/complicaciones , Teratoma/complicaciones , Variaciones en el Número de Copia de ADN , Femenino , Genoma Humano , Humanos , Melanoma/etiología , Melanoma/patología , Persona de Mediana Edad , Neoplasias Ováricas/patología , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas de Unión a Retinoblastoma/genética , Análisis de Secuencia de ADN , Teratoma/patología , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
In this study, we evaluated the magnetization properties of a magnetic alloy with single-crystalline cubic nanostructures, in order to clarify its magnetocrystalline anisotropy. Upon applying a specific annealing treatment to the CuNiFe base material, the precipitated magnetic particles grew into cubic granules, resulting in the formation of nanometric cubic single crystals of magnetic CuNiFe in a nonmagnetic Cu-rich matrix. The cubic nanostructures of CuNiFe were oriented along their crystallographic axis, in the <100> direction of the face-centered-cubic structure. We evaluated the static magnetization properties of the sample, which originated primarily from the CuNiFe nanocubes precipitated in the Cu-rich matrix, under an applied DC magnetic field. The magnetocrystalline anisotropy was readily observed in the magnetization curves. The <111> axis of the CuNiFe was observed to be the easy axis of magnetization. We also investigated the dynamic magnetization properties of the sample under an AC magnetic field. By subtracting the magnetic signal induced by the eddy current from the magnetization curves of the sample, we could obtain the intrinsic AC magnetization properties of the CuNiFe nanocubes.
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Cobre/química , Hierro/química , Magnetismo , Nanopartículas del Metal/química , Níquel/química , Anisotropía , CristalizaciónRESUMEN
Problems related to high levels of gaming and Internet usage are increasingly recognized as a potential public health burden across the developed world. The aim of this review was to present an international perspective on prevention strategies for Internet gaming disorder and related health conditions (e.g., Internet addiction), as well as hazardous gaming and Internet use. A systematic review of quantitative research evidence was conducted, followed by a search of governmental reports, policy and position statements, and health guidelines in the last decade. The regional scope included the USA, UK, Australia, China, Germany, Japan, and South Korea. Prevention studies have mainly involved school-based programs to train healthier Internet use habits in adolescents. The efficacy of selective prevention is promising but warrants further empirical attention. On an international scale, the formal recognition of gaming or Internet use as a disorder or as having quantifiable harms at certain levels of usage has been foundational to developing structured prevention responses. The South Korean model, in particular, is an exemplar of a coordinated response to a public health threat, with extensive government initiatives and long-term strategic plans at all three levels of prevention (i.e., universal, selective, and indicated). Western regions, by comparison, are dominated by prevention approaches led by non-profit organizations and private enterprise. The future of prevention of gaming and Internet problems ultimately relies upon all stakeholders working collaboratively in the public interest, confronting the reality of the evidence base and developing practical, ethical, and sustainable countermeasures.
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Conducta Adictiva/prevención & control , Política de Salud , Juegos de Video , Niño , Países Desarrollados , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Internacionalidad , Internet , Masculino , Salud PúblicaRESUMEN
We report a case ofrecurrent sigmoid cancer in which long-term disease control was achieved by intermittent oxaliplatin (L-OHP)administration. A 58-year-old woman underwent first-line chemotherapy with capecitabine and L-OHP(CapeOX) following peritoneal lymph node recurrence of sigmoid cancer. Tumor shrinkage was confirmed by a computed tomography (CT)scan following 4 courses of CapeOX treatment. However, L-OHP administration was discontinued by the 9 course due to peritoneal neuropathy. L-OHP was reintroduced following tumor progression confirmed by CT or elevation of carcinoembryonic antigen levels detected by a blood test. This stop-and-go strategy controlled lymph node recurrence effectively for over 5 years and was not associated with the development ofperitoneal neuropathy. We suggest that the intermittent administration ofL -OHP-containing chemotherapy is an important treatment option for some patients with advanced colorectal cancer, achieving effective long-term disease control with no associated peripheral neuropathy.
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Antineoplásicos/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Microglia, as well as other tissue-resident macrophages, arise from yolk sac progenitors. Thus, it is likely that the central nervous system environment is critical for the acquisition of a distinct microglial phenotype. Several microRNAs that are enriched in the brain play crucial roles in brain development and may also play a role in the differentiation of microglia. METHODS: To track the differentiation of hematopoietic cells into microglia, lineage-negative bone marrow cells were co-cultured with astrocytes in the absence or presence of microRNAs or their inhibitors. Microglia-like cells were identified as small, round cells that were immunopositive for CD11b, Iba1, CX3CR1, and triggering receptor expressed on myeloid cells (TREM)-2. RESULTS: Five microRNAs (miR-101a, miR-139-3p, miR-214*, miR-218, and miR-1186) were identified as modifiers of the differentiation of bone marrow-derived microglia-like cells. Among them, miR-101a facilitated the differentiation of bone marrow cells into microglia-like cells most potently. Small, round cells expressing CD11b, Iba1, CX3CR1, and TREM-2 were predominant in cells treated by miR-101a. miR-101a was abundantly expressed in non-microglial brain cells. Transfection of miR-101a into microglia significantly increased the production of IL-6 in response to LPS. Finally, miR-101a downregulated the expression of MAPK phosphatase-1. CONCLUSIONS: miR-101a, which is enriched in the brain, promotes the differentiation of bone marrow cells into microglia-like cells.
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Inflamación/metabolismo , Inflamación/patología , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Microglía/patología , Análisis de Varianza , Animales , Animales Recién Nacidos , Proteínas de Unión al Calcio/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Microglía/metabolismo , Células Mieloides/metabolismo , Oligonucleótidos Antisentido/farmacología , Receptores Inmunológicos/metabolismo , Transducción de Señal/efectos de los fármacos , TransfecciónRESUMEN
Water in confining geometries shows various anomalous properties related to its structure and dynamics compared with bulk water. Here, the dielectric constant of water as a function of separation in a graphite slab geometry was studied using molecular dynamics simulations. The dielectric constants of water were calculated from the orientational polarization of water molecules when an external electric field was applied parallel and normal to the slabs. The reduction of the dielectric constant of water compared with bulk water can be explained by investigating the structure and dynamics of water in slab geometries. We found a preferred orientation of water molecules in the layer closest to the graphite surface. The self-diffusion coefficient distribution of water molecules along the direction normal to the slabs was also computed. Highly mobile water molecules in the intermediate region were generated by the weak hydrogen bonding produced by the preferred orientation of water molecules in the layer. We concluded that the dielectric constant of water in the slab geometry is lower than that of bulk water because of the reduction of the polarization of water and the highly mobile water molecules in the intermediate region arising from the preferred orientation of water molecules.
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Grafito/química , Simulación de Dinámica Molecular , Agua/química , Campos Electromagnéticos , Enlace de Hidrógeno , Propiedades de SuperficieRESUMEN
AIMS: Microglia are the resident immune cells in the central nervous system, originating from haematopoietic-derived myeloid cells. A microglial cell is a double-edged sword, which has both pro-inflammatory and anti-inflammatory functions. Although understanding the role of microglia in pathological conditions has become increasingly important, histopathology has been the only way to investigate microglia in human diseases. METHODS: To enable the study of microglial cells in vitro, we here establish a culture system to induce microglia-like cells from haematopoietic cells by coculture with astrocytes. The characteristics of microglia-like cells were analysed by flow cytometry and functional assay. RESULTS: We show that triggering receptor expressing on myeloid cells-2-expressing microglia-like cells could be induced from lineage negative cells or monocytes by coculture with astrocytes. Microglia-like cells exhibited lower expression of CD45 and MHC class II than macrophages, a characteristic similar to brain microglia. When introduced into brain slice cultures, these microglia-like cells changed their morphology to a ramified shape on the first day of the culture. Moreover, we demonstrated that microglia-like cells could be induced from human monocytes by coculture with astrocytes. Finally, we showed that interleukin 34 was an important factor in the induction of microglia-like cells from haematopoietic cells in addition to cell-cell contact with astrocytes. Purified microglia-like cells were suitable for further culture and functional analyses. CONCLUSION: Development of in vitro induction system for microglia will further promote the study of human microglial cells under pathological conditions as well as aid in the screening of drugs to target microglial cells.
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Técnicas de Cultivo de Célula/métodos , Técnicas de Cocultivo/métodos , Células Madre Hematopoyéticas/fisiología , Microglía/citología , Microglía/fisiología , Monocitos/fisiología , Animales , Astrocitos/fisiología , Diferenciación Celular , Corteza Cerebral/citología , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Interleucinas/farmacología , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Médula Espinal/citologíaRESUMEN
A 61-year-old man was referred to us for investigation of acute abdominal pain. Computed tomography showed a 5.9 × 5.3 × 5.0 cm lump of food residue in the jejunum, and a large amount of free air and ascites around the liver and right paracolic gutter. He underwent emergency laparotomy for suspected peritonitis from perforation by a foreign body in the small intestine. We identified purulent exudate in the abdominal cavity and perforation of a jejunal cystic mass, attached ~40 cm from Treitz's ligament at the anti-mesenteric side of the jejunum. Based on a diagnosis of jejunal duplication with perforation, we resected that part of the small intestine and performed intra-abdominal drainage. Pathological findings confirmed the diagnosis of a perforated gastrointestinal stromal tumor (GIST) in a true jejunal diverticulum. Histopathological evidence suggests that intestinal pressure and/or hemorrhage can cause perforation in the background of a true jejunal diverticulum. To our knowledge, this is the first case report of a perforated GIST in a true jejunal diverticulum.
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Divertículo/etiología , Tumores del Estroma Gastrointestinal/etiología , Perforación Intestinal/etiología , Enfermedades del Yeyuno/etiología , Procedimientos Quirúrgicos del Sistema Digestivo , Divertículo/diagnóstico , Divertículo/patología , Divertículo/cirugía , Drenaje , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Perforación Intestinal/diagnóstico , Perforación Intestinal/patología , Perforación Intestinal/cirugía , Enfermedades del Yeyuno/cirugía , Yeyuno/patología , Yeyuno/cirugía , Laparotomía , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Alcoholics have a high prevalence of nicotine dependence, and smoking is a major contributor to their high mortality. Three weeks after admission to an addiction center in Japan, 193 alcoholic men who were participating in an 11-week concurrent inpatient smoking cessation and alcohol abstinence programs filled out an anonymous self-report questionnaire regarding smoking and drinking, and 6 months after the completion of the programs, 83 patients were asked to respond to a mailed questionnaire about their smoking and drinking status. Of the 193 subjects, 73.3% were current smokers, but many were highly motivated in regard to both smoking cessation and alcohol abstinence. The subjects' scores on a 0 to 10 point scale for rating motivation and confidence in regard to smoking cessation and smoking urge were significantly correlated with each other and with their scores for motivation and confidence in regard to alcohol abstinence and drinking urge. Three weeks after admission, varenicline treatment was well-tolerated, and the varenicline group had a high rate of smoking cessation than the smoker group not treated with varenicline (67.7% vs. 44.6%, p = 0.012). Forty-six (55.4%) of the 83 subjects who were mailed the questionnaire responded, and the drinking category was 'totally abstinent' in 35 subjects (42.2%), and 'mostly abstinent' in another 4 subjects (4.8%). Seventeen (20.5%) of the 83 subjects were non-smokers before treatment, but after treatment, 23 (50.0%) of the 46 responders and 20 (51.3%) of the 'totally or mostly abstinent' 39 responders were total or almost non-smokers. The response rate of 'totally or mostly abstinent' was higher among the 17 non-smokers before treatment than among the 66 smokers before treatment (70.6% vs. 40.9%, p = 0.033), and the age-adjusted odds ratio (95% confidence interval) for the response of 'totally or mostly abstinent' was 3.30 (1.03-10.56) for the non-smokers before treatment (vs. the smokers before treatment). In conclusion, smoking status had a great impact on the drinking status of treatment-seeking alcoholic men, and smoking cessation should be recommended to smoking alcoholics.
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Abstinencia de Alcohol , Alcoholismo/psicología , Alcoholismo/terapia , Pacientes Internos/psicología , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Fumar/psicología , Adulto , Anciano , Benzazepinas/administración & dosificación , Terapia Cognitivo-Conductual , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agonistas Nicotínicos/administración & dosificación , Quinoxalinas/administración & dosificación , Resultado del Tratamiento , Vareniclina , Adulto JovenRESUMEN
A 66-year-old woman was admitted to our hospital for massive ascites of unknown origin. Peritoneal mesothelioma was suspected because of her history of asbestos exposure. Diagnostic laparoscopy with biopsy of the peritoneum and greater omentum was performed. Pathological examination with immunostaining provided a definite diagnosis of malignant peritoneal mesothelioma. The patient underwent early postoperative induction therapy with pemetrexed and carboplatin, which resulted in a reduction in ascites. Laparoscopic biopsy contributed to the definite diagnosis of malignant peritoneal mesothelioma, and thereby, early induction of chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/patología , Mesotelioma/patología , Neoplasias Peritoneales/patología , Anciano , Ascitis/etiología , Biopsia , Carboplatino/administración & dosificación , Femenino , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Laparoscopía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Mesotelioma/complicaciones , Mesotelioma/tratamiento farmacológico , Mesotelioma Maligno , Pemetrexed , Neoplasias Peritoneales/complicaciones , Neoplasias Peritoneales/tratamiento farmacológicoRESUMEN
A 49-year-old female patient presented with lower abdominal pain and constipation. Computed tomography revealed left breast cancer with lymph node metastases, a peritoneal metastasis, bilateral hydronephrosis, and ovarian metastasis. The giant ovarian metastasis occupied the pelvic cavity and was responsible for her symptoms of digestive obstruction. Both ovaries were resected as a palliative measure. Three cycles of weekly paclitaxel were successfully administered, leading to the disappearance of malignant ascites. Hence, reduction surgery for ovarian metastasis in the treatment of breast cancer increased the effectiveness of the chemotherapy by improving the patient's general condition.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Ováricas/secundario , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/patología , Terapia Combinada , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Paclitaxel/uso terapéutico , Cuidados PaliativosRESUMEN
Hypoxic-ischemic brain injury induces metabolic dysfunction that ultimately leads to neuronal cell death. Astrocytes, a type of glial cell, play a key role in brain metabolism; however, their response to hypoxic-ischemic brain injury is not fully understood. Microglia were removed from murine primary mixed glial cultures to enrich astrocytes. Next, we explored genes whose expression is altered following oxygen-glucose deprivation using a microarray. Microarray analysis revealed that the expression of Nr4a1 and Nr4a3 is markedly increased in astrocyte-enriched cultures after 15 h of oxygen-glucose deprivation. The expression of both Nr4a1 and Nr4a3 was regulated by HIF-1α. At the protein level, NR4A1 was translocated from the nucleus to the cytoplasm following oxygen-glucose deprivation and co-localized with mitochondria in apoptotic cells; however, its localization was restored to the nucleus after reoxygenation. Oxygen-glucose deprivation causes an increase in NR4A1 mRNA in astrocytes as well as its nuclear to cytoplasmic transfer. Furthermore, reoxygenation enhances NR4A1 transcription and promotes its nuclear translocation.
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Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.
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OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.