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INTRODUCTION AND OBJECTIVES: The Scarborough Health Network joined the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) in fiscal year 2017-2018 with interest in tracking surgical outcomes in General and Vascular Surgery patients. Results of the ACS NSQIP program revealed poor outcomes in 30-day urinary tract infection (UTI) rates in this population group. Results were in the lowest quartile compared to peer hospitals. To improve patient care, SHN initiated a multi-pronged quality improvement plan (QIP). METHODS: The QIP focused on several improvements: (1) clarify the current state and conduct a root cause analysis, (2) determine a plan to encourage early removal of catheters in post-surgical patients, (3) enhance team communication in the pre-operative, operative and post-operative care environments, and (4) improve education around UTI prevention and treatment. RESULTS: This study demonstrates the success of the quality improvement plan to improve a peri-operative complication in surgical patients. By 2019, SHN saw a significant decrease in UTI rates, and became a top decile performer in ACS NSQIP. CONCLUSIONS: This study demonstrates the feasibility and success of implementing a quality improvement project, and its methods can be adapted at other hospital sites to improve patient care.
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Complicaciones Posoperatorias , Mejoramiento de la Calidad , Infecciones Urinarias , Humanos , Infecciones Urinarias/prevención & control , Infecciones Urinarias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Análisis de Causa RaízRESUMEN
PURPOSE: To evaluate patient-reported work ability of breast cancer patients, to compare scores with the Dutch general population, and to identify determinants of reduced work ability in breast cancer patients. METHODS: In a prospective cohort study, we identified 939 patients <67 years. Employed patients filled out the Work Ability Index (WAI) questionnaire before the start of radiotherapy treatment (baseline) and at 6, 18, and 30 months. Work ability was compared with a matched Dutch cancer-free population (n=3,641). The association between (clinical) characteristics and work ability over time was assessed using mixed-effects models. RESULTS: At baseline, 68% (n=641) of the respondents were employed and 64% (n=203) were employed at 30 months. Moderate or poor work ability was reported by 71% of patients at baseline, by 24% of the patients at 30 months and by 14% of the general population. Axillary lymph node dissection, (neo)adjuvant chemotherapy and locoregional radiotherapy were associated with reduced work ability. After 30 months, 18% of employed patients reported to have reduced their working hours, made substantial modifications to their work or were unable to work. CONCLUSION: Patient-reported work ability is strongly reduced during breast cancer treatment. Thirty months after treatment the proportion of women reporting poor or moderate work ability remains higher compared to the general population. Even though the proportion of women with paid employment is rather stable over time, substantial amendments in work are needed in 18% of patients. These findings emphasize the importance of informing patients on potential changes in work ability to allow shared decision making.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Empleo , Neoplasias de la Mama/terapia , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Países Bajos , Autoinforme , Evaluación de Capacidad de TrabajoRESUMEN
Caries progression seems to follow universal, predictable rates, depending largely on the caries severity in populations: the higher the caries severity, the higher the progression rates. Quantification of these rates would allow prediction of future caries increments. Our aim was to describe caries progression rates in the primary and permanent dentition in Western populations (not in lesions) of children and adolescents. Therefore, we systematically searched MEDLINE-PubMed, Embase, CINAHL, and the Cochrane library for studies reporting caries progression data. Eligibility criteria were reporting empirical data from at least 2 full-mouth dental caries examinations in a closed cohort during a follow-up of at least 3 y, a first examination after 1974, a second examination before the age of 22 y, caries assessed as dentine caries (d3/D3), and caries reported in dmfs/DMFS (decayed, missing, and filled surfaces), dmft/DMFT (decayed, missing, and filled teeth), or caries-free participants. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we described the results for the primary and permanent dentition in a systematic review, performed a meta-analysis for the caries incidence rate in the permanent dentition, and conducted multivariate, hierarchical meta-regression analyses for the caries incidence rate and the increments in DMFS and DMFT. Of the 6,343 unique studies retrieved, 43 studies (56,376 participants) were included for systematic review and 32 for meta-analyses (39,429 participants). The annual decline in caries-free children in the permanent dentition ranged from 0.8% to 10.2%. The annual increment ranged from 0.07 to 1.77 in DMFS and from 0.06 to 0.73 in DMFT. The pooled caries incidence rate was 0.11 (0.09-0.13) per person-year at risk. Meta-regression analyses showed that the methods of individual studies influenced pooled caries incidence rates and increments in DMFS and DMFT. This should be taken into account in planning and evaluation of oral health care services. However, the caries incidence rate is promising for prediction of future caries increments in populations.
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Caries Dental/diagnóstico , Caries Dental/patología , Progresión de la Enfermedad , Adolescente , Niño , Preescolar , Índice CPO , Dentición Permanente , Humanos , Análisis de Regresión , Adulto JovenRESUMEN
miRNAs play a crucial role in cancer development and progression. However, results on the impact of miRNAs on drug sensitivity and tumor biology vary, and most studies to date focussed on either increasing or decreasing miRNA expression levels. Therefore, the current study investigated the role of different expression levels of miR-130a-3p and miR-148a-3p on drug resistance and tumor biology in four esophageal squamous cell carcinoma cell lines. Interestingly, up- and downregulation of both miRNAs significantly increased sensitivity towards chemotherapy. MiRNA modulation also reduced adherence and migration potential, and increased apoptosis rates. Target analyses showed that up- and downregulation of both miRNAs activated the apoptotic p53-pathway via increased expression of either BAX (miR-148a-3p) or Caspase 9 (miR-130a-3p). miR-148a-3p downregulation seemed to mediate its effects primarily via regulation of Bim rather than Bcl-2 levels, whereas we found the opposite scenario following miR-148a-3p upregulation. A similar effect was observed for miR-130a-3p regulating Bcl-2 and XIAP. Our data provide the first evidence that miRNA modulation in both directions may lead to similar effects on chemotherapy response and tumor biology in esophageal squamous cell carcinoma. Most interestingly, up- and downregulation seem to mediate their effects via modulating the balance of several validated or predicted targets.
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Resistencia a Antineoplásicos , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , MicroARNs/metabolismo , ARN Neoplásico/metabolismo , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Humanos , MicroARNs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Neoplásico/genéticaRESUMEN
The tumor microenvironment (TME) of cancer cells is regarded as a strong determinant for cancer development and acquisition of metastatic potential of cancer cells. Because of its influence on tumorigenesis, the TME increasingly gained attention in research within the last years. Activated fibroblasts, so-called cancer-associated fibroblasts (CAFs), which are the most prominent cell type in the stromal compartment, are responsible for the synthesis, deposition and remodeling of the extracellular matrix in tumor stroma thus creating a favorable microenvironment for cancer cells. Besides, they secrete paracrine factors, such as growth factors, chemokines and exosomes impacting on proliferation, invasion and cell signaling of cancer cells. Molecular mechanisms responsible for activation of fibroblasts and regulation of metastatic microenvironment are complex and not yet fully elucidated. However, mounting evidence suggests that miRNAs play a powerful role in the communication between cancer cells and TME. Via regulation of various signaling pathways, release of cytokines/growth factors or exosomes, miRNAs are able to regulate tumor promoting effects of CAFs. In this review, we describe baseline differences in miRNAs signatures between CAFs and normal fibroblasts and highlight the influence of miRNAs on cell signaling within CAFs.
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Fibroblastos Asociados al Cáncer/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Proteínas de Neoplasias/genética , Neoplasias/metabolismo , Transducción de Señal/genética , Fibroblastos Asociados al Cáncer/patología , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Movimiento Celular , Proliferación Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Exosomas/química , Exosomas/metabolismo , Matriz Extracelular/química , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , MicroARNs/clasificación , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/clasificación , Neoplasias/genética , Neoplasias/patología , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Different countries are currently reporting a substantial increase in the incidence rates of papillary thyroid microcarcinoma (PTMC). OBJECTIVE: Presentation of diagnosis and surgical therapy of PTMC and discussion of a more conservative approach, such as active surveillance. MATERIAL AND METHODS: Overview of the current guidelines from different countries and analysis of recent publications reporting the results of active surveillance of PTMC from Japan, Korea and the USA. RESULTS: The majority of international guidelines for PTMC recommends thyroid lobectomy as the gold standard. Active surveillance as an alternative procedure is described in the Japanese guidelines (JSTS/JAES). Present surveillance studies including more than 1700 patients report a tumor growth in 8-14% of the cases during a median follow-up of up to 75 months. Tumor growth and lymph node metastases are detected most frequently in younger patients (below 40-50 years). CONCLUSION: Active surveillance might serve as an alternative treatment option for older patients with PTMC. Since the median follow-up periods are currently not long enough, it seems difficult to draw definite conclusions of this procedure right now.
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Neoplasias de la Tiroides , Tiroidectomía , Carcinoma Papilar/cirugía , Humanos , Neoplasias de la Tiroides/cirugíaRESUMEN
Sclerosing angiomatoid nodular transformation of the spleen (SANT) is a benign, extremely rare vascular lesion of the spleen with unknown pathogenesis. SANT is often discovered incidentally, and can sometimes be found in patients with a history of cancer. Based on absent definitive radiological signs and varying growth patterns, distinction from malignant processes such as metastasis can be very difficult. Therefore, surgical resection of the spleen is indicated in most cases of patients with history of cancer. We report a case of a bifocal manifestation of SANT in the spleen in a patient with history of colon cancer and newly-diagnosed metachronous liver metastases.
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Colectomía , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Histiocitoma Fibroso Benigno/patología , Neoplasias Hepáticas/secundario , Neoplasias Primarias Secundarias/patología , Neoplasias del Bazo/patología , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias del Colon/química , Hepatectomía , Histiocitoma Fibroso Benigno/química , Histiocitoma Fibroso Benigno/diagnóstico por imagen , Histiocitoma Fibroso Benigno/cirugía , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/química , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/química , Neoplasias Primarias Secundarias/diagnóstico por imagen , Neoplasias Primarias Secundarias/cirugía , Reoperación , Esplenectomía , Neoplasias del Bazo/química , Neoplasias del Bazo/diagnóstico por imagen , Neoplasias del Bazo/cirugía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Neoadjuvant radiochemotherapy [n(R)CT] has become the standard of care in the multimodal therapy concept for patients with locally advanced esophageal cancer; however, optimal timing of surgery is not clearly defined. OBJECTIVES: The study analyzed whether the length of the interval between completion of n(R)CT and surgery can affect the postoperative outcome, tumor response and long-term survival. MATERIAL AND METHODS: A total of 106 patients with adenocarcinoma and squamous cell carcinoma of the esophagus, treated between 2006 and 2013, were included in this study. On the basis of the median time interval to surgery, patients were divided into two groups [group A ≤ 40 days (n = 54) and group B > 40 days (n = 52)] and compared concerning demographic data, preoperative risk scores, morbidity, outcome, tumor response and long-term survival. RESULTS: The groups were comparable in terms of demographics, preoperative condition of the patients, complications and outcome; however, group A showed a trend towards a higher mortality risk as preoperatively assessed by the physiological and operative severity score for the enumeration of mortality and morbidity in esophagogastric surgery patients (O-POSSUM) (p = 0.064) and group B showed a trend towards a higher rate of complete responders (p = 0.097). CONCLUSION: Concerning perioperative morbidity and mortality, delayed surgery after n(R)CT showed no benefit for the patient's outcome; however, the rate of complete tumor response was higher in patients with a time interval of more than 40 days, although this did not influence long-term survival or recurrence rates.
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Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Despite multimodal therapeutic options, esophageal cancer is still among the most deadly malignancies. In the past decade, targeted therapy has shown great potential in other cancers, but data on esophageal carcinoma are still rare. Five potential new molecular targets in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) were investigated for their expression characteristics: vascular endothelial growth factor receptor (VEGFR)-3, human epidermal growth factor receptor-2, stem cell growth factor receptor, tissue inhibitors of metalloproteinase (TIMP)-4 and TIMP-3. One hundred seventy-one EAC and ESCC tissue samples obtained from patients undergoing esophagectomy from 2000 to 2008 were included. Clinical data were evaluated retrospectively. Immunohistochemical staining was performed using tumor tissue with and without neoadjuvant treatment and healthy tissue. For samples without neoadjuvant treatment, expression of all targets was higher in tumor tissue than in healthy tissue except for VEGFR-3 (>98% expression in both tissues). For TIMP-4, TIMP-3 and stem cell growth factor receptor, trends to higher expression in tumor tissue were also found in EAC and ESCC that had received neoadjuvant treatment. Using Matched-pair analysis, we compared target expression in tumor tissue with and without neoadjuvant treatment. Only TIMP-3 had significantly lower expression in neoadjuvant treated tumor tissue (EAC: P = 0.059, ESCC: P = 0.006). TIMP-4, TIMP-3 and VEGFR-3 appear to qualify for targeted therapy in esophageal cancer because of their high expression in neoplastic tissue. TIMP-3 appears to be downregulated in neoadjuvantly treated esophageal cancer, and VEGFR-3 shows high expression in healthy mucosa leading to severe side effects by molecular targeting. Thus, TIMP-4 seems the most promising target.
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Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor ErbB-2/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adenocarcinoma/terapia , Anciano , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Inhibidor Tisular de Metaloproteinasa-4RESUMEN
Chlorine dioxide (ClO2) is a disinfestant used to control pathogens in water. To determine if interactions between inorganic ions and pH levels effect ClO2 activity in vitro, concentrations of ClO2 (0, 1, 3, 5, 7, 9, 22, 24, 46, 58, and 70 mg/liter) were mixed for 10 min in solutions containing a nitrogen and hard water solution with equal concentrations of ammonium, nitrate, and synthetic hard water (0 and 100 mg/liter) and a divalent metal ion solution with equal concentrations of copper, iron, manganese, and zinc (0, 1, 3, and 5 mg/liter) at pH 5 and 8. Macro- and microconidia of Fusarium oxysporum f. sp. narcissi or conidia and aleuriospores of Thielaviopsis basicola were injected into each suspension for 30 s, captured on filter paper disks that were flushed with water, and plated on 50% potato dextrose agar. Spore germination was quantified after 1 day. ClO2 activity had a similar effect on both fungal species and all types of propagules with interactions among the divalent metal ion solution, nitrogen and hard water solution, and pH treatments. A higher concentration of ClO2 was required at pH 8 than at pH 5 to achieve a lethal dose resulting in 50% mortality of spores (LD50). The addition of the divalent metal ion solution required an increase in ClO2 concentration to maintain a LD50. When combined with the nitrogen and hard water solution, the divalent metal ion solution placed a higher demand on ClO2 at pH 5 and a lower demand on ClO2 at pH 8, thus requiring an increase and decrease in a ClO2 concentration, respectively, to achieve a LD50. Chlorine dioxide doses resulting in 50% mortality ranged from 0.5 to 7.0 mg/liter for conidia of F. oxysporum, 0.5 to 11.9 mg/liter for conidia of T. basicola, and 15.0 to 45.5 mg/liter for aleuriospores of T. basicola.
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OBJECTIVE: To develop and test a procedure for continuous measurement of backrest elevation in critical care for enhancing the precision of this measurement for research purposes. DESIGN: Descriptive, correlational. SETTING AND MEASUREMENTS: Backrest elevation, defined as the height of the head of the bed in degrees of elevation above horizontal, can be continuously monitored by using two transducers, one attached to the bed frame just distal to the head of the bed gatch and another attached to the bed frame at the top of the bed. By monitoring the differential head pressure between the two pressure channels, the height of the head of the bed can be calculated. A total of 30 random measurements of backrest elevation, from 0 degrees to 60 degrees, were taken by using the backrest elevation measurement on the bed frame, a handheld protractor, and the pressure differential between two transducers attached to the bed frame. Data collectors recorded one measurement independent of the other measurements. All measurements were conducted on the same bed. RESULTS: When the transduced method was compared with measurements by using a protractor, the Bland-Altman analysis technique yielded upper and lower limits of agreement of 8.93 degrees and -5.91 degrees, respectively. The bias was 1.51 degrees, and the precision was 3.71 degreees. CONCLUSIONS: The measurement technique described here was developed for research purposes to add precision to research studies examining the appropriate height of the backrest. However, the procedure could be used in a continuous quality improvement process to enhance compliance with patient care procedures involving backrest elevation or to confirm actual nursing practice and its correlation with patient outcome. In light of the risks associated with the use of supine positioning in critically ill and mechanically ventilated patients, the information gained from continuous measurement of backrest position could be an extremely valuable research tool.
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Lechos , Cuidados Críticos , Neumonía por Aspiración/etiología , Respiración Artificial/efectos adversos , Posición Supina , Diseño de Equipo , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , InvestigaciónRESUMEN
The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.
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Contaminantes Ambientales/toxicidad , Estrógenos/toxicidad , DDT/toxicidad , Estradiol/análogos & derivados , Estradiol/farmacología , Estrógenos/metabolismo , Etanol/toxicidad , Fulvestrant , Humanos , Receptores de Estrógenos/metabolismo , Tamoxifeno/farmacología , Células Tumorales Cultivadas , Vitelogeninas/biosíntesisRESUMEN
This review addresses the most current and widely used methods of assessing childhood and adolescent externalizing disorders. Interviews, rating scales, and self-report instruments are described, and their strengths and weaknesses are discussed. Direct observational techniques in naturalistic and analogue settings are also reviewed. Throughout the article, commentary is offered regarding the psychometric adequacy and clinical validity of these instruments. It is suggested that, although the instruments presently used to assist in diagnosing externalizing disorders generally possess adequate reliability and representational validity, evidence of elaborative validity is lacking. Clinicians and researchers are encouraged to adopt a broader conceptualization of the diagnostic process, to question existing standards for establishing validity, and to consider alternative means of demonstrating diagnostic utility.
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Trastornos de la Conducta Infantil/diagnóstico , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Déficit de la Atención y Trastornos de Conducta Disruptiva/diagnóstico , Déficit de la Atención y Trastornos de Conducta Disruptiva/psicología , Niño , Trastornos de la Conducta Infantil/psicología , Trastorno de la Conducta/diagnóstico , Trastorno de la Conducta/psicología , Humanos , Entrevista Psicológica , Escalas de Valoración Psiquiátrica , Pruebas Psicológicas , Autoevaluación (Psicología) , Conducta SocialRESUMEN
Expression of the inducible nitric oxide synthase (iNOS) gene in rat mesangial cells is differentially triggered by IL-1beta and cAMP predominantly at the transcriptional level. The 5'-flanking region of the rat iNOS gene contains several binding sites for transcription factors potentially involved in cytokine and cAMP signaling such as nuclear factor-kappaB/Rel, CCAAT/enhancer-binding protein (C/EBP), and cyclic AMP-responsive element-binding protein/ATF. We tested promoter activities of serial and site-directed deletion mutants of iNOS-chloramphenicol acetyltransferase reporter genes after transient transfection and stimulation of mesangial cells. A region between bp -277 and -111 bearing a CCAAT/enhancer-binding protein-response element was found to be critical for cAMP-mediated gene induction but dispensable for IL-1beta inducibility. Moreover, a minimal promoter ranging from the transcriptional start site up to -111 containing a kappaB site is sufficient to confer IL-1beta-mediated iNOS promoter activation. Consistent with these findings, an electrophoretic mobility shift assay shows the appearance of an IL-1beta-inducible nuclear factor-kappaB p50/p65 heterodimeric complex. Using probes containing C/EBP-binding sites from the iNOS gene revealed further binding of different complexes, all of which were strongly inducible by cAMP and to a lower extent also by IL-1beta. Abs against cyclic AMP-responsive element-binding protein, C/EBPbeta, and C/EBPdelta were able to partially supershift single complexes, suggesting the participation of these transcription factors in the regulation of iNOS gene expression by cAMP and IL-1beta. Finally, we show that both cAMP and IL-1beta strongly induce steady-state levels of C/EBPbeta and C/EBPdelta mRNA levels. These data demonstrate that IL-1beta and cAMP use distinct as well as partially overlapping sets of transcriptional activators to modulate iNOS gene expression in rat mesangial cells.
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AMP Cíclico/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Mesangio Glomerular/enzimología , Interleucina-1/farmacología , Óxido Nítrico Sintasa/genética , Animales , Proteínas Potenciadoras de Unión a CCAAT , Células Cultivadas , ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/fisiología , Regiones Promotoras Genéticas , ARN Mensajero/análisis , Ratas , Activación TranscripcionalRESUMEN
The oestrogen receptor belongs to the superfamily of nuclear receptors. Classically, nuclear receptors are thought to reside either in the nucleus or in the cytoplasm where they interact with their ligand which induces a conformational change that exposes the DNA binding domain. This is followed by dimerisation and binding of their corresponding response elements. By interacting with the transcriptional apparatus they then either activate or repress the transcription of target genes. However, this is a highly simplified view, since the activated oestrogen receptor interacts with other signal transduction pathways and its intrinsic transcriptional activity is highly influenced by phosphorylation and by its interaction with other proteins. This is clearly observed when the oestrogenicity of antioestrogens is tested since some compounds activate the receptor in yeast, but not in mammalian cells. However, when specific kinases are activated antioestrogens can also function as oestrogens in mammalian cells. Moreover, components of the MAP kinase and perhaps the cAMP and other pathways are activated before the receptor even enters the nucleus. Thus, when analysing the effects of oestrogenic compounds, it is important to assay both their potency as activators of transcription as the effects caused by interactions with other signal transduction pathways. This may be possible by combining assay methods, such as direct in vitro measurement of interaction between a potential oestrogenic chemical and the receptor or the yeast E-screen, with methods that are based on mammalian cells or whole animals. An alternative is to assay gene expression directly by methods such as differential display, where the expression of both genes known to be regulated directly by the receptor and genes regulated by other pathways can be monitored. Thereby it may be possible to assign different responses to the activation of distinct pathways.
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Estrógenos/genética , Regulación de la Expresión Génica , Receptores de Estrógenos/agonistas , Animales , Estrógenos/análisis , Estrógenos/farmacología , Humanos , Receptores de Estrógenos/análisis , Receptores de Estrógenos/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.
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Medios de Contraste/química , Fosfatidilcolinas/química , Ultrasonografía Doppler Transcraneal/métodos , Acústica , Análisis de Varianza , Anestésicos por Inhalación/química , Animales , Argón/química , Distribución de Chi-Cuadrado , Perros , Etano/química , Fluorocarburos/química , Isoflurano/química , Masculino , Pentanos/química , Ultrasonografía Doppler en ColorRESUMEN
OBJECTIVE: To determine how often the management of patients with blunt facial trauma was altered by plain roentgenograms or facial computed tomographic (CT) scans compared with findings from physical examination. METHOD: This is a retrospective review of consecutive patients admitted with blunt facial trauma and evaluated by the Division of Plastic Surgery from 1988 to 1994. Physical findings were correlated with fractures detected by plain roentgenograms or facial CT reports. Treatment plans were reviewed to determine how management was altered by radiographic studies. Hospital charges were determined for the various studies. RESULTS: One hundred thirty-seven records were reviewed. Thirty patients had only lacerations and no fractures. Two hundred forty-three fractures were detected on physical examination among 98 patients (91.5%). One hundred two patients (95.3%) had facial CT scans and 85 patients (79.4%) had facial plain films obtained. Radiographic findings identified a total of 255 fractures among 107 patients (78%). Ninety-four patients (87.9%) required operative interventions for these facial fractures. Only 19 patients (17.8%) had management altered by radiographic findings: CT scan (7 patients) and plain films (12 patients). The management of 88 facial fractures (34.5%) in this series did not appear to be altered by x-ray findings. Computed tomography was most beneficial in the management of orbital fractures (N = 7). Plain films affected mostly the evaluation of mandibular injuries (N = 7). Selective use of CT scan could lead to hospital savings estimated at $11,864 for the diagnosis of facial fractures after blunt trauma. CONCLUSION: Physical examination reliably assessed the facial skeleton for clinically significant fractures in the majority of patients. In an alert and cooperative patient, CT scan is not required before operative repair in all cases. CT scans are expensive, time-consuming, and labor-intensive and in selected cases add little clinical information to that obtained by physical examination and plain films.
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Traumatismos Faciales/diagnóstico por imagen , Examen Físico/normas , Tomografía Computarizada por Rayos X/normas , Heridas no Penetrantes/diagnóstico por imagen , Adolescente , Adulto , Anciano , Ahorro de Costo , Traumatismos Faciales/terapia , Femenino , Precios de Hospital , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/economía , Heridas no Penetrantes/terapiaRESUMEN
The separation of enantiomers of pantoprazole sodium, omeprazole and lansoprazole by capillary zone electrophoresis using bovine serum albumin (BSA) as the chiral selector is described. Baseline separation of the three structurally related drugs was obtained after optimization of the most important experimental parameters. For this purpose, influences such as BSA concentration, pH and concentration of 1-propanol as organic modifier on the separation were investigated. Increasing concentrations of BSA improved the chiral resolution but lowered the sensitivity of the detection system. Discrimination of the enantiomers was observed only in a narrow pH range of 7-8. An optimum of pH 7.4 was a good compromise in terms of enantio-resolution and peak shape. 1-Propanol when added to the buffer system, improved the peak shape of the analytes and the resolution. The optimized method has been validated for pantoprazole sodium and is useful for routine analysis.