RESUMEN
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.
Asunto(s)
Neoplasias Endometriales , Tumores Estromáticos Endometriales , Neoplasias Ováricas , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Neoplasias Uterinas , Persona de Mediana Edad , Femenino , Humanos , Neoplasias Uterinas/patología , Tumores Estromáticos Endometriales/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Biomarcadores de TumorRESUMEN
BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).
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Drenaje , Ictericia Obstructiva , Neoplasias Pancreáticas , Stents , Humanos , Drenaje/métodos , Drenaje/instrumentación , Drenaje/efectos adversos , Neoplasias Pancreáticas/complicaciones , Masculino , Femenino , Anciano , Ictericia Obstructiva/etiología , Ictericia Obstructiva/terapia , Ictericia Obstructiva/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Stents/efectos adversos , Resultado del Tratamiento , Cuidados Preoperatorios , Anciano de 80 o más Años , Periodo Preoperatorio , SeguridadRESUMEN
BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.
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Convulsiones Febriles , Niño , Humanos , Lactante , Convulsiones Febriles/diagnóstico , Convulsiones Febriles/epidemiología , Estudios Retrospectivos , Japón/epidemiología , Convulsiones/diagnóstico , Convulsiones/epidemiologíaRESUMEN
Specific amino acid substitutions in degenerin mechano-gated channels (DEGs) of C. elegans convert these channels into constitutively active mutants that induce the degeneration of neurons where DEGs are expressed. Acid-sensing ion channel-2a (ASIC2a), a proton-gated cation channel predominantly expressed in central neurons, is a mammalian ortholog of DEGs, and it can remain unclosed to be cytotoxic once the same mutations as the DEG mutants are introduced into its gene. Here we show that heterozygous transgenic (Tg) rats expressing ASIC2a-G430F (ASIC2aG430F), the most active form of the gain-of-function mutants, under the control of the intrinsic ASIC2a promoter exhibited marked cerebellar maldevelopment with mild whole-brain atrophy. The Tg rats were small and developed an early-onset ataxic gait, as evidenced by rotarod and footprint tests. The overall gross-anatomy of the Tg brain was normal just after birth, but a reduction in brain volume, especially cerebellar volume, gradually emerged with age. Histological examination of the adult Tg brain revealed that the cell-densities of cerebellar Purkinje and granule cells were markedly reduced, while the cytoarchitecture of other brain regions was not significantly altered. RT-PCR and immunoblot analyses demonstrated that ASIC2aG430F transcripts and proteins were already present in various regions of the neonatal Tg brain before the deforming cerebellum became apparent. These results suggest that, according to the spatiotemporal pattern of the wild-type (WT) ASIC2a gene expression, the ASIC2aG430F channel induced lethal degeneration in Tg brain neurons expressing both ASIC2aG430F and ASIC2a channels.
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Canales Iónicos Sensibles al Ácido , Cerebelo , Mutación con Ganancia de Función , Canales Iónicos Sensibles al Ácido/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Animales , Cerebelo/patología , Mutación , RatasRESUMEN
BACKGROUND: Febrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence. METHODS: This was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002-December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007-February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013-April 2016), BCT was indicated for FCSE resistant to fPHT or PB. RESULTS: The rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40). CONCLUSIONS: While the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.
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Estado Epiléptico , Anticonvulsivantes/uso terapéutico , Niño , Protocolos Clínicos , Estudios de Cohortes , Humanos , Pronóstico , Convulsiones/tratamiento farmacológico , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Klüver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain.
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Leucodistrofia de Células Globoides , Humanos , Adulto , Lactante , Masculino , Femenino , Anciano , Preescolar , Leucodistrofia de Células Globoides/diagnóstico , Leucodistrofia de Células Globoides/genética , Leucodistrofia de Células Globoides/patología , Autopsia , Galactosilceramidasa/genética , Mutación , Imagen por Resonancia MagnéticaRESUMEN
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function.
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Encéfalo/metabolismo , Metabolómica/métodos , Mitocondrias/metabolismo , Peptidil-Prolil Isomerasa F/genética , Sepsis/metabolismo , Animales , Temperatura Corporal , Modelos Animales de Enfermedad , Técnicas de Inactivación de Genes , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Masculino , Ratones , Poro de Transición de la Permeabilidad Mitocondrial , Especies Reactivas de Oxígeno/metabolismo , Sepsis/etiología , Sepsis/genética , Sepsis/mortalidadRESUMEN
In 2020, the worldwide incidence and mortality of colorectal cancer (CRC) were third and second, respectively. As the 5-y survival rate is low when CRC is diagnosed at an advanced stage, a reliable method to predict CRC susceptibility is important for preventing the onset and development and improving the prognosis of CRC. Therefore, we focused on the normal colonic mucosa to investigate changes in gene expression that may induce subsequent genetic alterations that induce malignant transformation. Comprehensive gene expression profiling in the normal mucosa adjacent to colon cancer (CC) compared with tissue from non-colon cancer patients was performed. PCR arrays and qRT-PCR revealed that the expression of 5 genes involved in the immune response, including MYD88, was increased in the normal mucosa of CC patients. The expression levels of MYD88 were strikingly increased in precancerous normal mucosa specimens, which harbored no somatic mutations, as shown by immunohistochemistry. Microarray analysis identified 2 novel RNA-controlling molecules, EXOSC3 and CNOT4, that were significantly upregulated in the normal mucosa of CC patients and were clearly visualized in the nuclei. Forced expression of EXOSC3 and CNOT4 in human colonic epithelial cells increased the expression of IFNGR1, MYD88, NFκBIA, and STAT3 and activated ERK1/2 and JNK in 293T cells. Taken together, these results suggested that, in the inflamed mucosa, EXOSC3- and CNOT4-mediated RNA stabilization, including that of MYD88, may trigger the development of cancer and can serve as a potential predictive marker and innovative treatment to control cancer development.
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Neoplasias del Colon/genética , Complejo Multienzimático de Ribonucleasas del Exosoma/genética , Perfilación de la Expresión Génica/métodos , Factor 88 de Diferenciación Mieloide/genética , Proteínas de Unión al ARN/genética , Factores de Transcripción/genética , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular , Neoplasias del Colon/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Mutación , Factor 88 de Diferenciación Mieloide/metabolismo , Pronóstico , Transducción de SeñalRESUMEN
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
In the perioperative period, hypoxemia and hyperoxia are crucial factors that require attention, because they greatly affect patient prognoses. The pulse oximeter has been the only noninvasive monitor that can be used as a reference of oxygenation in current anesthetic management; however, in recent years, a new monitoring method that uses the oxygen reserve index (ORi™) has been developed by Masimo Corp. ORi is an index that reflects the state of moderate hyperoxia (partial pressure of arterial oxygen [PaO2] between 100 and 200 mmHg) using a non-unit scale between 0.00 and 1.00. ORi monitoring performed together with percutaneous oxygen saturation (SpO2) measurements may become an important technique in the field of anesthetic management, for measuring oxygenation reserve capacity. By measuring ORi, it is possible to predict hypoxemia and to detect hyperoxia at an early stage. In this review, we summarize the method of ORi, cautions for its use, and suitable cases for its use. In the near future, the monitoring of oxygen concentrations using ORi may become increasingly common for the management of respiratory function before, after, and during surgery.
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Oximetría , Oxígeno , Análisis de los Gases de la Sangre , Humanos , Hipoxia , Presión ParcialRESUMEN
A 79-year-old male patient had a huge choledocholithiasis that was difficult to remove and underwent endoscopic retrograde biliary drainage. He complained of hematemesis upon admission to our hospital. Endoscopic retrograde cholangiography showed bleeding from the papilla of Vater and revealed an upper filling defect with a large stone in the common bile duct. Furthermore, computed tomography detected an aneurysm close to the stone. Considering the occurrence of a ruptured pancreaticoduodenal artery aneurysm, we diagnosed this condition as hemobilia. Through angiography, we also detected a saccular aneurysm in the posterior superior pancreaticoduodenal artery (PSPDA);subsequently, selective transcatheter arterial embolization (TAE) was performed. However, bleeding persisted after TAE;therefore, we performed second-time embolization for other PSPDA branches. Consequently, hemostasis was achieved. To date, bleeding has not reoccurred. The pancreaticoduodenal artery constitutes a complex arcade;hence, cases of extremely difficult hemostasis by embolization have been reported. Herein, we have presented a life-saving case of choledocholithiasis treated with TAE for biliary bleeding from a PSPDA aneurysm rupture.
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Aneurisma Roto , Coledocolitiasis , Embolización Terapéutica , Hemobilia/diagnóstico , Anciano , Arteria Hepática , Humanos , MasculinoRESUMEN
OBJECTIVES: To evaluate the proportion of children presenting to the emergency department (ED) with altered mental status who demonstrate nonconvulsive seizures on reduced-lead electroencephalography (EEG), and to further investigate the characteristics, treatment, and outcomes in these patients compared with patients without nonconvulsive seizures. STUDY DESIGN: In this retrospective cohort study, we reviewed the database and medical records of pediatric patients (aged <18 years) in a single ED between May 1, 2016, and April 30, 2018. We first determined the proportion of nonconvulsive seizures among patients with altered mental status (Glasgow Coma Scale <15). We then compared the clinical presentation, demographic data, clinical diagnosis, EEG results, treatment, and outcomes of patients with altered mental status with nonconvulsive seizures and those without nonconvulsive seizures. RESULTS: In total, 16.9% of the patients with altered mental status (41 of 242; 95% CI, 12.2%-21.6%) evaluated by EEG had detectable nonconvulsive seizure, equivalent to 4.4% (41 of 932) of all patients with altered mental status presenting at our hospital. More than 80% of patients monitored for nonconvulsive seizures had a previous history of seizures, often febrile. Patients with nonconvulsive seizures were older (median, 68.5 vs 36.1 months) and had a higher Pediatric Cerebral Performance Category score at presentation (median, 2.0 vs 1.0). In addition, the proportion of patients admitted to the intensive care unit was significantly higher in the patients with nonconvulsive seizures (30.3% vs 15.0%). However, total duration of hospitalization, neurologic sequelae, and 30-day mortality rate did not differ between the 2 groups. CONCLUSIONS: A relatively high percentage of pediatric patients with altered mental status in the ED experience nonconvulsive seizures. The use of reduced-lead EEG monitoring in the ED might facilitate the recognition and treatment of nonconvulsive seizures, especially among patients with a history of seizures.
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Electroencefalografía/métodos , Epilepsia Generalizada/diagnóstico , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Salud Mental , Escala del Estado Mental , Preescolar , Epilepsia Generalizada/epidemiología , Epilepsia Generalizada/fisiopatología , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Japón/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15â¯years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6â¯months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3⯱â¯22.0â¯mg/dl, 1â¯month: 63.8⯱â¯21.6â¯mg/dl, 6â¯months: 92.3⯱â¯63.6â¯mg/dl, pâ¯=â¯0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15⯱â¯0.06â¯ng/dl, 1â¯month: 1.00⯱â¯0.16â¯ng/dl, 6â¯months: 0.98⯱â¯0.14â¯ng/dl, pâ¯=â¯0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.
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Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Levetiracetam/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Tirotropina/sangre , Tiroxina/sangre , Triglicéridos/sangre , Adolescente , Anticonvulsivantes/administración & dosificación , Carbamazepina/administración & dosificación , Niño , Preescolar , HDL-Colesterol/sangre , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Femenino , Humanos , Levetiracetam/administración & dosificación , Masculino , Estudios Prospectivos , Tirotropina/efectos de los fármacos , Tiroxina/efectos de los fármacosRESUMEN
The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.
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Modelos Animales de Enfermedad , Audición/fisiología , Enfermedad de Meniere/inducido químicamente , Nistagmo Patológico/inducido químicamente , Cloruro de Potasio , Animales , Inyección Intratimpánica , Masculino , Enfermedad de Meniere/fisiopatología , Nistagmo Patológico/fisiopatología , Ratas , Ratas WistarRESUMEN
BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound-guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs. METHODS: We immunocytochemically stained INSM1 and Ki-67 in 14 PNET cases, and according to the 2017 World Health Organisation criteria, seven PNET Grade 1 cases, four Grade 2 cases and three Grade 3/neuroendocrine carcinoma cases were identified. As a control for INSM1 and Ki-67 expression, we used cytological specimens from 15 cases of pancreatic ductal adenocarcinoma. RESULTS: In PNET cases, INSM1-expressing tumour cells were identified in all cytological specimens of PNET. The median INSM1 expression rate in Grade 1 cases was 49.8% (mean ± standard deviation: 55.1 ± 12.5%, min: 39.3%, max: 74.1%), and in Grade 2 and Grade 3/neuroendocrine carcinoma cases was 81.1% (mean ± standard deviation: 77.6 ± 18.6%, min: 50.3%, max: 100%). However, there was no correlation between INSM1 and Ki-67 expression (r = -0.15). The median expression rate in PNET cases was 64.3%, which was significantly higher than that in pancreatic ductal adenocarcinoma cases (P < 0.0001). CONCLUSION: INSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound-guided fine needle aspiration cytology can accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular-targeted therapy.