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BACKGROUND: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. OBJECTIVE: To investigate the impact of early-life infections on AD development. METHODS: This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. RESULTS: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. CONCLUSION: Infections in early life are associated with AD development in infancy and early childhood.
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Asma , Dermatitis Atópica , Eccema , Rinitis Alérgica , Asma/complicaciones , Estudios de Casos y Controles , Preescolar , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Eccema/complicaciones , Femenino , Humanos , Recién Nacido , Embarazo , Factores de RiesgoRESUMEN
Objective: To explore the help seeking efficacy and social assistance willingness of medical staff during major public health events, so as to provide basis for improving the psychological resources and service quality of medical staff and further optimizing the prevention and treatment policies. Methods: In February 2020, a convenient sampling method was used to conduct an online questionnaire survey on medical staff in Henan Province, and a total of 2136 questionnaires were collected. Among them, there were 1940 valid questionnaires, and the effective recovery rate was 90.82%. The questionnaire of help seeking efficacy and willingness to social assistance under epidemic situation was used to investigate the help seeking efficacy and willingness of medical staff. The frequency and rate (%) were used to analyze the overall situation of medical staff's help seeking efficacy and social assistance willingness. The differences among different demographic variables were tested by χ(2) test. Results: Among the 1940 medical and nursing staff, 18.81% (365/1940) did not know how to obtain appropriate psychological assistance. Compared with the low age group, the medical staff in the high age group had the ability of information query, the ability to occupy knowledge resources, the ability to distinguish rumors and facts and the sense of efficacy of obtaining appropriate medical help, and the difference was statistically significant (P<0.05) . The willingness of medical and nursing staff to actively cooperate with the government, maintain social stability and volunteer work were 99.43% (1929/1940) , 98.81% (1917/1940) and 97.11% (1884/1940) . Conclusion: The medical staff had a higher sense of help seeking efficacy and willingness to social assistance. It is necessary to further strengthen the resource support of psychological, social and humanistic care for medical staff.
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Intención , Salud Pública , Humanos , Cuerpo Médico , Organizaciones , Encuestas y CuestionariosRESUMEN
BACKGROUND: Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. OBJECTIVES: To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. METHODS: A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single-nucleotide polymorphisms in 14 susceptibility genes, and HLA-Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. RESULTS: Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. CONCLUSIONS: Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.
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Proteínas de Unión al ADN/genética , Fármacos Dermatológicos/farmacología , Resistencia a Medicamentos/genética , Metotrexato/farmacología , Psoriasis/tratamiento farmacológico , Adulto , Anciano , Pueblo Asiatico/genética , China , Fármacos Dermatológicos/uso terapéutico , Femenino , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Psoriasis/diagnóstico , Psoriasis/genética , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study was to make noninvasive quantitative analysis of ceramide (CER) in skin of healthy Chinese population by high performance liquid chromatography tandem mass spectrometry. METHODS: Seven healthy subjects were selected and the stratified skin samples were available using cyanoacrylate adhesion method. High performance liquid chromatography tandem mass spectrometry, use ceramide Subclass Standard C42H85NO3 Quantification of the 12 corresponding ceramide subclass in the epidermis on the 7 skin samples, which cannot get all the standard of ceramides subclass since the stratum corneum ceramide is complex and diverse. Data were collected and analyzed using full-flow lipid analysis software (LipidSearch). RESULTS: All the seven skin samples contained 12 subclasses of ceramide and the samples were quantitated with ceramide C42H85NO3 standard. The average contents were 33.63, 27.59, 108.57, 220.75, 149.20, 43.06, and 22.78 µg/mL, respectively. CONCLUSION: Ceramide is an important lipid in the epidermis and is closely related to the skin barrier function. There are 12 subtypes of ceramide detected in the skin of Chinese healthy people, and there is a difference in the concentration between individuals. The difference may be associated with the skin barrier condition, and may also be related to the unavoidable error in the process of sampling, treatment, and detection.
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Ceramidas/análisis , Epidermis/química , Pueblo Asiatico , Cromatografía Líquida de Alta Presión , Humanos , Piel , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. METHODS: One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. RESULTS: A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05). CONCLUSIONS: A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation.
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Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/secundario , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Adulto , Anciano , Biopsia con Aguja Fina , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Modelos Logísticos , Ganglios Linfáticos/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , UltrasonografíaRESUMEN
OBJECTIVES: Psychotic symptoms are commonly observed among heroin users. Low serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the relationship between serum BDNF levels and psychotic symptoms in heroin dependence are lacking. METHOD: A total of 31 heroin-dependent patients who had never experienced psychotic symptoms during heroin consumption and 21 patients with a history of psychotic symptoms were consecutively recruited. We measured by enzyme-linked immunosorbent assay (ELISA) serum BDNF levels during early abstinence. A gender- and age-matched sample of healthy controls was also recruited and underwent measurement of BDNF. RESULTS: BDNF levels were significantly lower in patients with psychotic symptoms than in those without psychotic symptoms (P<0.001). BDNF levels were not found to be correlated with sex, age, age of onset, duration of heroin use, average daily dose of heroin use, frequency of heroin use, SDS scores, BAI scores and BDI scores in the psychotic subsamples (all P>0.05). CONCLUSIONS: Our findings suggest that heroin-dependent patients with psychotic symptoms share some of the neurotrophic insult that characterizes schizophrenia and psychosis.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Dependencia de Heroína/sangre , Dependencia de Heroína/psicología , Trastornos Psicóticos/sangre , Trastornos Psicóticos/complicaciones , Adulto , Estudios de Casos y Controles , Femenino , Dependencia de Heroína/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/psicologíaRESUMEN
OBJECTIVES: The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. MATERIALS AND METHODS: Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. RESULTS: OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. CONCLUSION: Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.
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Carcinoma de Células Escamosas/química , Neoplasias de la Boca/química , Lesiones Precancerosas/química , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Antagonistas de Andrógenos/farmacología , Andrógenos/farmacología , Anilidas/farmacología , Animales , Apoptosis , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Ciclina D1/efectos de los fármacos , Ciclina D1/metabolismo , Dihidrotestosterona/farmacología , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Neoplasias de la Boca/patología , Nitrilos/farmacología , Receptores Androgénicos/análisis , Compuestos de Tosilo/farmacologíaRESUMEN
AIMS: Serum ferritin has been found closely related with diabetes and glucose metabolism, but its impact on diabetic nephropathy remains unknown. This study aimed to explore the association between serum ferritin and microalbuminuria in Type 2 diabetes. METHODS: Eight hundred and fifty-one subjects with Type 2 diabetes were selected from a cohort participating in a glycaemic control study in Taiwan in 2008. We used urine albumin:creatinine ratio to define microalbuminuria; serum ferritin was divided into quartiles for analysis. Logistic regression and trend tests were used to delineate the association between serum ferritin and microalbuminuria. RESULTS: Subjects with diabetes with higher ferritin tended to have more metabolic disorders, higher high-sensitivity C-reactive protein and higher prevalence of microalbuminuria. Compared with those in the lowest quartile, subjects with diabetes in the highest ferritin quartile were 55% (P = 0.029) more likely to have microalbuminuria. After controlling for demographics, metabolic profiles and other inflammatory markers, the association between serum ferritin levels and microalbuminuria remained significant (P for trend < 0.001). This independent relationship was not changed either for those who had better glycaemic control or those who had not used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSIONS: The current study shows hyperferritinemia may be an independent risk factor of nephropathy in patients with Type 2 diabetes.
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Albuminuria/etiología , Diabetes Mellitus Tipo 2/etiología , Nefropatías Diabéticas/etiología , Ferritinas/sangre , Albuminuria/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , TaiwánRESUMEN
Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.
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Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Derrame Pleural Maligno/genética , ARN/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma del Pulmón , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib , Exones , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Derrame Pleural Maligno/tratamiento farmacológico , Quinazolinas/uso terapéuticoRESUMEN
To reduce the driving voltage, and hence enhance the power efficiency of OLEDs, the mobility of the various carrier transport layers needs to be increased. Buckminsterfullerene (C(60)) has been proposed to be one possible alternative conductive electron transport layer (ETL) to enhance the power efficiency in OLEDs, due to its high conductivity and the formation of an ohmic contact with the LiF/Al cathode. The optical properties of a nanocomposite of C(60) with LiF (C(60):LiF) and its potential as an efficient ETL in OLEDs was studied. With proper optimization of the device structure, a more than 50% improvement in the power efficiency, without sacrificing the high EQE, in optimized fluorescent OLEDs with the use of C(60):LiF nanocomposite ETL was achieved.
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Treatment strategy of esophageal cancer mainly depends on accurate staging. At present, no single ideal staging modality is superior to another in preoperative tumor-node-metastasis (TNM) staging of patients with esophageal cancer. We aimed to investigate the efficacy of endoscopic ultrasonography (EUS) and positron emission tomography-computed tomography (PET-CT) for staging of esophageal cancer. We retrospectively studied 118 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy with or without neoadjuvant chemoradiotherapy (CRT) over a near 3-year period between January 2005 and November 2008 at a tertiary hospital in Taiwan. Patients were separated into two groups: without neoadjuvant CRT (group 1, n= 28) and with CRT (group 2, n= 90). Medical records of demographic data and reports of EUS and PET-CT of patients before surgery were reviewed. A database of clinical staging by EUS and PET-CT was compared with one of pathological staging. The accuracies of T staging by EUS in groups 1 and 2 were 85.2% and 34.9%. The accuracies of N staging by EUS in groups 1 and 2 were 55.6% and 39.8%. The accuracies of T and N staging by means of PET-CT scan were 100% and 54.5% in group 1, and were 69.4% and 86.1% in group 2, respectively. In group 2, 38 of 90 patients (42.2%) achieved pathologic complete remission. Among them, two of 34 (5.9%) and 12 of 17 (70.6%) patients were identified as tumor-free by post-CRT EUS and PET-CT, respectively. EUS is useful for initial staging of esophageal cancer. PET-CT is a more reliable modality for monitoring treatment response and restaging. Furthermore, the accuracy of PET-CT with regard to N staging is higher in patients who have undergone CRT than those who have not.
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Carcinoma de Células Escamosas/diagnóstico , Endosonografía , Neoplasias Esofágicas/diagnóstico , Imagen Multimodal , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Esofagectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
BACKGROUND: Impetigo herpetiformis (IH) is a rare skin disorder that occurs during pregnancy. It was previously associated with high maternal and fetal mortality and morbidity, but now has a better prognosis. CASE REPORT: We report a case of a pregnant woman with IH who presented with generalized erythematous pustular eruptions in the 32nd week of gestation. The IH progressed rapidly, and gestational hypertension was observed in the 36th week. The lesions did not subside, despite treatment with corticosteroids and phototherapy. She delivered a healthy male baby via cesarean section in the 37th week. One month after her delivery, her skin returned to normal, except for residual pigmentation, with complete recovery 3 months postpartum. CONCLUSION: An experienced medical team comprising obstetricians, dermatologists, perinatologists and neonatologists is critical to aggressively treat this life-threatening specific dermatosis of pregnancy and to prevent ensuing complications, such as fluid and electrolyte imbalance, secondary infection and placental insufficiency.
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Hipertensión Inducida en el Embarazo/diagnóstico , Impétigo/diagnóstico , Complicaciones Infecciosas del Embarazo/diagnóstico , Corticoesteroides/uso terapéutico , Adulto , Antibacterianos/uso terapéutico , Calcio/uso terapéutico , Cesárea , Ciclosporina/uso terapéutico , Dermatitis Herpetiforme/diagnóstico , Dermatitis Herpetiforme/tratamiento farmacológico , Dermatitis Herpetiforme/terapia , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Impétigo/complicaciones , Impétigo/tratamiento farmacológico , Recién Nacido , Nacimiento Vivo , Masculino , Fototerapia , Embarazo , Complicaciones Infecciosas del Embarazo/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Although evidence suggests that subjective memory complaints (SMCs) could be a risk factor for dementia, the relationship between SMCs and objective memory performance remains controversial. Old adults with or without mild cognitive impairment (MCI) may represent a highly heterogeneous group, based partly on the demonstrated variability in the level of executive function among those individuals. It is reasonable to speculate that the accuracy of the memory-monitoring ability could be affected by the level of executive function in old adults. OBJECTIVE: This study investigated the effects of executive function level on the consistency between SMCs and objective memory performance while simultaneously considering demographic and clinical variables in nondemented older adults. SETTING: Participants were recruited from both the memory clinics and local communities. PARTICIPANTS: Participants comprised 65 cognitively normal (CN) older adults and 54 patients with MCI. MEASUREMENTS: Discrepancy scores between subjective memory evaluation and objective memory performance were calculated to determine the degree and directionality of the concordance between subjective and objective measures. Demographic, emotional, genetic, and clinical information as well as several executive function measurements were collected. RESULTS: The CN and MCI groups exhibited similar degrees of SMC; however, the patients with MCI were more likely to overestimate their objective memory ability, whereas the CN adults were more likely to underestimate their objective memory ability. The results also revealed that symptoms of depression, group membership, and the executive function level together predicted the discrepancy between the subjective and objective measures of memory function; however, the executive function level retained its unique predictive ability even after the symptoms of depression, group membership, and other factors were controlled for. CONCLUSION: Although both noncognitive and cognitive factors were necessary for consideration, the level of executive function may play a unique role in understanding the equivocal relationship of the concurrence between subjective complaints and objective function measures. Through a comprehensive evaluation, high-risk individuals (i.e., CN individuals heightened self-awareness of memory changes) may possibly be identified or provided with the necessary intervention during stages at which objective cognitive impairment remains clinically unapparent.
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Disfunción Cognitiva/psicología , Demencia/psicología , Depresión/psicología , Función Ejecutiva/fisiología , Memoria/fisiología , Anciano , Cognición/fisiología , Demencia/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors. MATERIALS AND METHODS: We analyzed EGFR exons 18-21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled. RESULTS: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases). CONCLUSION: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Exones , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. The purpose of the present study was to investigate the EGFR mutation rate in MPEs of lung adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.
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Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación , Derrame Pleural/genética , Adenocarcinoma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Derrame Pleural/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidoresRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to elucidate the mechanism of YC-1{3-(5'-hydroxy methyl-2'-furyl)-1-benzylindazole}-induced human renal carcinoma cells apoptosis and to evaluate the potency of YC-1 in models of tumour growth in mice. EXPERIMENTAL APPROACH: YC-1-mediated apoptosis was assessed by analysis of MTT, SRB, DAPI staining and flow cytometry analysis. Knockdown of JNK protein was achieved by transient transfection using siRNA. The mechanisms of action of YC-1 on different signalling pathways involved were studied using western blot. Fas clustering was analysed by confocal microscopy and in vivo efficacy was examined in a A498 xenograft model. KEY RESULTS: YC-1 displayed cytotoxicity in renal carcinoma cells at 10(-7)-10(-8) M. Increased condensation of chromatin was observed and an increase in the cell population in subG1 phase. Moreover, YC-1 triggered mitochondria-mediated and caspase-dependent pathways. YC-1 significantly induced Fas ligand expression, but did not modify either the protein levels of death receptors or ligands. In addition, Fas clustering in cells responsive to YC-1 was observed, suggesting involvement of a Fas-mediated pathway. Furthermore, YC-1 markedly induced phosphorylation of JNK and a JNK inhibitor, SP600125, and siRNA JNK1/2 significantly reversed YC-1-induced cytotoxicity and protein expression. We suggest that YC-1 induced JNK phosphorylation, the upregulation of FasL and Fas receptor clustering to promote the activation of caspases 8 and 3, resulting in apoptosis. Finally, we demonstrated the antitumour effect of YC-1 in vivo. CONCLUSIONS AND IMPLICATIONS: These data suggest that YC-1 is a good candidate for development as an anticancer drug.
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Apoptosis/efectos de los fármacos , Carcinoma de Células Renales/tratamiento farmacológico , Activadores de Enzimas/farmacología , Indazoles/farmacología , Animales , Carcinoma de Células Renales/patología , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 8/efectos de los fármacos , Caspasa 8/metabolismo , Cromatina/efectos de los fármacos , Cromatina/metabolismo , Relación Dosis-Respuesta a Droga , Activadores de Enzimas/administración & dosificación , Proteína Ligando Fas/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Fase G1/efectos de los fármacos , Humanos , Indazoles/administración & dosificación , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación/efectos de los fármacos , Receptor fas/efectos de los fármacos , Receptor fas/metabolismoRESUMEN
OBJECTIVES: Rhabdomyoma, the most common primary fetal cardiac tumor, is often associated with tuberous sclerosis (TS). We aimed to evaluate outcome in cases diagnosed with fetal cardiac rhabdomyoma. METHODS: This study presents 11 cases with fetal cardiac rhabdomyoma. In addition, all relevant published cases of antenatally diagnosed cardiac rhabdomyoma since 1982 were identified from MEDLINE. We evaluated the following risk factors associated with clinical impact and perinatal outcome: family history of TS, gestational age at diagnosis, tumor size, site and number of tumors, tumor progression, and associated intracardiac and extracardiac anomalies. RESULTS: In this meta-analysis, 138 cases, including nine newly added by us, were categorized into Group A (107 live babies) and Group B (16 neonatal deaths and 15 intrauterine fetal deaths). Univariate analysis showed that large cardiac tumors (P < 0.0001), fetal dysrhythmia (P < 0.0001) and hydrops (P < 0.0001) were strong predictors of neonatal outcome. Tumor size >or= 20 mm (relative risk (RR), 20.6; 95% CI, 2.2-195.9; P = 0.009) and fetal dysrhythmia (RR, 13.6; 95% CI, 2.9-62.3; P = 0.001) were significantly associated with neonatal morbidity. TS, present in 85/133 (63.9%) cases, was significantly associated with multiple cardiac tumors (P < 0.0001) and family history of TS (P = 0.02). CONCLUSIONS: Large tumor size and hydrops are significantly associated with poor neonatal outcome, whereas family history of TS and multiple fetal cardiac tumors are associated with TS. Any sonographic detection of a fetal cardiac tumor should warrant further investigation for the possible presence of associated disorders.
Asunto(s)
Enfermedades Fetales/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico por imagen , Rabdomioma/diagnóstico por imagen , Ultrasonografía Prenatal/métodos , Ecocardiografía , Femenino , Enfermedades Fetales/patología , Corazón Fetal/patología , Edad Gestacional , Neoplasias Cardíacas/patología , Humanos , Lactante , Análisis Multivariante , Embarazo , Resultado del Embarazo , Pronóstico , Rabdomioma/patología , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/genéticaRESUMEN
The challenge of heart transplantation in patients with situs inversus is reconstruction of the systemic venous return. Herein we have presented 2 cases of complex congenital heart disease with atriovisceral situs inversus. Both of the patients shared many common cardiac anomalies, such as a single ventricle, a single AV valve with severe regurgitation, and severe pulmonary stenosis. We completed the venous connection in 2 different ways. In the first case, the donor inferior vena cava (IVC) was anastomosed to the recipient left-sided IVC directly, making the heart slightly counterclockwise rotated. In the second case, the IVC venous reconnection was accomplished by a composite conduit made of recipient right atrium.
Asunto(s)
Trasplante de Corazón , Situs Inversus/cirugía , Adolescente , Anastomosis Quirúrgica , Electrocardiografía , Resultado Fatal , Femenino , Lateralidad Funcional , Humanos , Vena Cava Inferior/cirugíaRESUMEN
BACKGROUND: Standard dosing regimens with lithium usually require significant time before the optimal serum concentration is achieved. METHOD: The present study compares a new method (Method 1) with two existing ones (Methods 2 and 3) for dosing of individual patients with lithium, to more rapidly achieve optimum concentrations. Thirty patients, who were on lithium therapy and who met the inclusion criteria, were evaluated. RESULTS: The correlation coefficient between true and expected concentrations were 0.518 (P < 0.01), 0.555 (P < 0.01) and 0.424 (P = 0.019) respectively. The mean +/- standard deviation of the difference from the expected concentrations of three methods were 0.02 +/- 0.20 mEq/L, 0.31 +/- 0.22 and -0.27 +/- 0.25 respectively. CONCLUSION: Method 1 was the least biased and most accurate among three methods for predicting the optimal therapeutic lithium dose in Taiwanese psychiatric patients.
Asunto(s)
Antidepresivos/farmacocinética , Antimaníacos/farmacocinética , Carbonato de Litio/farmacocinética , Trastornos Mentales/tratamiento farmacológico , Adulto , Anciano , Antidepresivos/sangre , Antidepresivos/uso terapéutico , Antimaníacos/sangre , Antimaníacos/uso terapéutico , Pueblo Asiatico , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Femenino , Humanos , Carbonato de Litio/sangre , Carbonato de Litio/uso terapéutico , Masculino , Trastornos Mentales/sangre , Persona de Mediana Edad , TaiwánRESUMEN
OBJECTIVE: To investigate the impact and protective effect of tauroursodeoxycholic acid (TUDCA) on the autophagy of nerve cells in rats with acute spinal cord injury. MATERIALS AND METHODS: Seventy-two 6-8-week-old male Sprague-Dawley (SD) rats were selected and were randomly divided into a sham operation group, a saline control group and a TUDCA treatment group (high and low dose groups). The experimental animals were sacrificed at 24 hours, 5 days and 10 days after spinal cord injury. The Basso, Beattie, Bresnahan locomotor scale was used to assess the hind limb locomotor function after the rats were injured but before sudden death. Electron microscopy, hematoxylin and eosin (HE) staining, TUNEL assays and immunohistochemistry techniques were used to observe the autophagy of the cells. Western blotting was used to analyze the expression of the autophagy-related factor Beclin-1 and the apoptosis-related factor caspase-3, and reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the above proteins. RESULTS: The locomotor scores of the rats in the saline group were significantly reduced, their Beclin-1 expression levels in neurons were decreased, and caspase-3 expression was increased. The hind limb locomotor scores of rats in the TUDCA groups were decreased, with no difference between the high- and low-dose groups. Beclin-1 expression in their neurons was increased, and caspase-3 expression was decreased; there was a significant difference when compared with the control group, while there was no significant difference between the high- and low-dose groups. CONCLUSIONS: TUDCA significantly activates the neuronal autophagic expression in rats with acute spinal cord injury to inhibit the apoptosis of nerve cells; therefore, it has a protective effect on neurons.