Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Front Endocrinol (Lausanne) ; 12: 705567, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34335476

RESUMEN

Background: Limited data have shown that, compared to uncomplicated twin pregnancies, pregnancies complicated by twin-twin transfusion syndrome (TTTS), a life-threatening condition, are associated with higher maternal serum levels of both human chorionic gonadotropin (hCG) and thyroid hormones. With the continuing expansion of assisted reproductive technologies, the rate of twin pregnancies, including those complicated by TTTS and associated hyperemesis gravidarum, is expected to increase further. Therefore, detailed descriptions of the maternal and fetal clinical outcomes of maternal thyrotoxicosis linked to TTTS can be useful for timely diagnosis and management. However, such descriptions are currently lacking in the literature. Case Presentation: We report the case of a 30-year-old woman carrying a monochorionic twin pregnancy complicated by TTTS that induced a relapse of severe hyperemesis gravidarum with overt non-autoimmune hyperthyroidism at 17 weeks of gestation. Following fetoscopic laser coagulation (FLC), both hyperemesis and hyperthyroidism improved within 1 week. Conclusions: The present experience contributes to the knowledge base on maternal thyrotoxicosis linked to TTTS and can be useful in the diagnosis and treatment of future cases; it also emphasizes the need for a high degree of clinical suspicion and for close collaboration between endocrinologists and obstetricians. Another key point is that TTTS-associated hyperemesis gravidarum and maternal hyperthyroidism should be considered in the differential diagnosis of refractory or relapsing hyperemesis gravidarum in women with monochorionic twin pregnancy, because this condition may require more stringent supportive treatment before and during the FLC procedure when the mother is overtly hyperthyroid.


Asunto(s)
Gonadotropina Coriónica/efectos adversos , Transfusión Feto-Fetal/complicaciones , Hiperemesis Gravídica/terapia , Hipertiroidismo/terapia , Coagulación con Láser/métodos , Adulto , Femenino , Fetoscopía/métodos , Humanos , Hiperemesis Gravídica/etiología , Hiperemesis Gravídica/patología , Hipertiroidismo/etiología , Hipertiroidismo/patología , Embarazo , Embarazo Gemelar , Pronóstico
2.
J Pharm Biomed Anal ; 159: 341-347, 2018 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-30025299

RESUMEN

The use of DNA aptamers in biosensors for the quantification of pharmaceuticals in the clinics would help to overcome the limitations of antibody-based detection for small molecules. The interest for such systems is proven by the ever-increasing number of aptamer-based solutions for analytics proposed in the literature as proof-of-concept demonstrators. Despite such diversity, these platforms often lack a comparative assessment of their performances against the current standard of practice in the clinics when using real samples. We employed an aptamer against tobramycin discovered in our laboratory to quantify through surface plasmon resonance the concentration of the antibiotic in clinical samples obtained from patients treated with tobramycin and undergoing therapeutic drug monitoring. We then compared the performances of our detection strategy against the current standard of practice. Our results show how, using adequate calibration and matrix complexity reduction, DNA aptamer-based direct assays can assess clinically relevant concentrations of small molecules in patient serum and with good correlation to current standards used in the clinics.


Asunto(s)
Aptámeros de Nucleótidos/sangre , Monitoreo de Drogas/normas , Tobramicina/sangre , Antibacterianos/sangre , Monitoreo de Drogas/métodos , Humanos , Resonancia por Plasmón de Superficie
3.
J Forensic Leg Med ; 42: 51-5, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27239954

RESUMEN

Significantly increased blood ketone body levels can be occasionally observed in the forensic setting in situations other than exposure to cold, diabetic or alcoholic ketoacidosis. Though infrequent, these cases do occur and deserve thorough evaluation in order to establish appropriate differential diagnoses and quantify the role that hyperketonemia may play in the death process. Starvation ketoacidosis is a rare cause of metabolic acidosis and is a phenomenon that occurs normally during fasting, as the body switches from carbohydrate to lipid energy sources. The levels of ketonemia in starvation ketoacidosis is usually mild in comparison to those seen in diabetic or alcoholic ketoacidosis. In the clinical setting, several cases of starvation-induced ketoacidosis mainly associated with gastric banding, pregnancy, malnutrition and low-carbohydrate diets have been reported. However, starvation ketosis causing severe metabolic acidosis has been rarely described in the medical literature. In the realm of forensic pathology, starvation-induced hyperketonemia has been rarely described. In this paper we present the postmortem biochemical results observed in situations of suspected starvation-induced hyperketonemia that underwent medico-legal examination. In all these cases, the diagnosis of starvation induced-hyperketonemia and the subsequent ketoacidosis was established per exclusionem based on all postmortem investigation findings. A review of the literature pertaining to the clinical diagnosis of starvation ketoacidosis is also provided.


Asunto(s)
Cetosis/metabolismo , Cambios Post Mortem , Inanición/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Acetona/sangre , Adulto , Albúminas/metabolismo , Biomarcadores/metabolismo , Nitrógeno de la Urea Sanguínea , Creatinina/metabolismo , Femenino , Patologia Forense , Humanos , Cetosis/diagnóstico , Masculino , Persona de Mediana Edad , Líquido Pericárdico/metabolismo , Prealbúmina/metabolismo , Proteínas/metabolismo , Ácido Úrico/metabolismo , Cuerpo Vítreo/metabolismo
4.
Swiss Med Wkly ; 145: w14242, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26709671

RESUMEN

UNLABELLED: Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. STUDY OBJECTIVES: Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. METHODS: Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. RESULTS: A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. CONCLUSIONS: In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED.


Asunto(s)
Sobredosis de Droga/diagnóstico , Sobredosis de Droga/orina , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Suiza , Adulto Joven
5.
BMC Cancer ; 15: 300, 2015 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-25928859

RESUMEN

BACKGROUND: Epithelial-mesenchymal transition (EMT) is involved in important malignant features of cancer cells, like invasion, metastatic potential, anti-apoptotic and stem-cell like phenotypes. Among several transcription factors, SNAI2/SLUG is supposed to play an essential role for EMT. METHODS: Paraffin embedded tumor samples from 63 patients with metastatic non-small cell lung cancer, enrolled in a randomized phase II trial, were prospectively collected, 53 samples qualified for further analysis. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of SNAI2/SLUG, estrogen receptor 1 (ESR1) and matrix-metalloproteinases (MMP) mRNA expression. RESULTS: Clinical features like age, gender, performance status, histological subtype and stage were similarly distributed among SNAI2/SLUG positive and negative patients. SNAI2/SLUG was significantly, inversely correlated with ESR1 mRNA expression (p < 0.0001). In contrast, MMP2 (p = 0.387), MMP7 (p = 0.396) and MMP9 mRNA expression (p = 0.366) did not correlate with SNAI2/SLUG. Patients with high SNAI2/SLUG expression (grouped by median expression) had a worse outcome. Median overall survival in patients with high SNAI2/SLUG expression was 5.7 months versus 11.6 months with low SNAI2/SLUG expression (p = .038). Inversely, patients with high ESR1 expression (grouped by median expression) had an improved median OS with 10.9 months vs. 5.0 months in the low expression group (p = .032). In multivariate analysis, SNAI2/SLUG2 (p = .022) and ESR1 (p = .017) separately were independent prognostic factors for survival. CONCLUSION: SNAI2/SLUG is prognostic of patients' outcome. The strong inverse correlation with ESR1 indicates a significant impact of estrogen receptor pathway regarding these malignant features.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Receptor alfa de Estrógeno/biosíntesis , Factores de Transcripción/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Receptor alfa de Estrógeno/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/biosíntesis , Transducción de Señal , Factores de Transcripción de la Familia Snail , Factores de Transcripción/genética , Resultado del Tratamiento
6.
Drug Test Anal ; 7(9): 797-803, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25641775

RESUMEN

Insulin determination in blood sampled during post-mortem investigation has been repeatedly asserted as being of little diagnostic value due to the rapid occurrence of decompositional changes and blood haemolysis. In this study, we assessed the feasibility of insulin determination in post-mortem serum, vitreous humour, bile, and cerebrospinal and pericardial fluids in one case of fatal insulin self-administration and a series of 40 control cases (diabetics and non-diabetics) using a chemiluminescence enzyme immunoassay. In the case of suicide by insulin self-administration, insulin concentrations in pericardial fluid and bile were higher than blood clinical reference values, though lower than post-mortem serum concentration. Insulin concentrations in vitreous (11.50 mU/L) and cerebrospinal fluid (17.30 mU/L) were lower than blood clinical reference values. Vitreous insulin concentrations in non-diabetic control cases were lower than the estimated detection limit of the method. These preliminary results tend to confirm the usefulness of insulin determination in vitreous humour in situations of suspected fatal insulin administration. Additional findings pertaining to insulin determination in bile, pericardial, and cerebrospinal fluid would suggest that analysis performed in post-mortem serum and injection sites could be complemented, in individual cases, by investigations carried out in alternative biological fluids. Lastly, these results would indicate that analysis with chemiluminescence enzyme immunoassay may provide suitable data, similar to analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoradiometric assay, to support the hypothesis of insulin overdose.


Asunto(s)
Insulina/análisis , Cambios Post Mortem , Anciano , Bilis/química , Diabetes Mellitus , Femenino , Humanos , Técnicas para Inmunoenzimas/métodos , Insulina/administración & dosificación , Insulina/sangre , Insulina/líquido cefalorraquídeo , Límite de Detección , Mediciones Luminiscentes/métodos , Masculino , Persona de Mediana Edad , Líquido Pericárdico/química , Cuerpo Vítreo/química
7.
J Transl Med ; 12: 160, 2014 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-24906218

RESUMEN

BACKGROUND: HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide. METHODS: Immunohistochemistry (IHC) and HER2 dual-colour silver in situ hybridization (SISH) as single methods (IHC/SISH) and gene-protein platform combining both methods on one slide (gene/protein) were performed in randomly collected 100 cases of gastric adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining. RESULTS: 96 of 100 samples were assessable. In the gene/protein staining, pathologists were able to assess gene amplification and consequent protein expression at the single cell level. In comparison trials, gene amplification was observed in 14.6% by both, conventional SISH and gene/protein platform (agreement 100%; Kappa-coefficient κ = 1.0). Protein expression scores by IHC were 70.8% (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There were complete concordances in IHC assessment of cases with score 0 (100.0%; κ = 1). High concordances are shown in score 1+ (98.96%; κ = 0.947) and 3+ (96.88%; κ = 0.825) cases and good concordances in 2+ cases (95.83%; κ = 0.728). CONCLUSIONS: This novel combined platform has the advantage of being able to evaluate both gene and the protein status in the same cancer cell and may be of particular interest for research and patient's care. ARTICLE CATEGORY: Disease Biomarker.


Asunto(s)
Hibridación in Situ/métodos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/diagnóstico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plata/química , Neoplasias Gástricas/metabolismo
8.
Nat Chem Biol ; 10(7): 598-603, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24907901

RESUMEN

For many drugs, finding the balance between efficacy and toxicity requires monitoring their concentrations in the patient's blood. Quantifying drug levels at the bedside or at home would have advantages in terms of therapeutic outcome and convenience, but current techniques require the setting of a diagnostic laboratory. We have developed semisynthetic bioluminescent sensors that permit precise measurements of drug concentrations in patient samples by spotting minimal volumes on paper and recording the signal using a simple point-and-shoot camera. Our sensors have a modular design consisting of a protein-based and a synthetic part and can be engineered to selectively recognize a wide range of drugs, including immunosuppressants, antiepileptics, anticancer agents and antiarrhythmics. This low-cost point-of-care method could make therapies safer, increase the convenience of doctors and patients and make therapeutic drug monitoring available in regions with poor infrastructure.


Asunto(s)
Monitoreo de Drogas/métodos , Proteínas Luminiscentes/química , Proteínas Recombinantes de Fusión/química , Antiarrítmicos/sangre , Anticonvulsivantes/sangre , Antineoplásicos/sangre , Técnicas Biosensibles , Monitoreo de Drogas/economía , Monitoreo de Drogas/instrumentación , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunosupresores/sangre , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Fotograbar , Sistemas de Atención de Punto , Ingeniería de Proteínas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo
9.
Br J Clin Pharmacol ; 78(5): 1090-101, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24938850

RESUMEN

AIM: This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. METHODS: All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®). RESULTS: A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%), central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc . Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg(-1) , at extended intervals to achieve adequate concentrations. CONCLUSIONS: This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.


Asunto(s)
Antibacterianos/sangre , Gentamicinas/sangre , Recién Nacido/sangre , Recien Nacido Prematuro/sangre , Modelos Biológicos , Antibacterianos/administración & dosificación , Peso al Nacer , Peso Corporal , Estudios de Cohortes , Simulación por Computador , Relación Dosis-Respuesta a Droga , Inmunoensayo de Polarización Fluorescente , Gentamicinas/administración & dosificación , Edad Gestacional , Humanos , Tasa de Depuración Metabólica , Medicina de Precisión , Análisis de Regresión , Estudios Retrospectivos
10.
Forensic Sci Int ; 241: e28-30, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24856626

RESUMEN

ß-hydroxybutyrate concentrations were determined in blood and synovial fluid in a series of medico-legal cases including hypothermia fatalities, individuals found dead in a cold environment and non-hypothermia cases with various, non-traumatic causes of death. Hypothermia was considered to be the cause of death according to circumstantial elements indicating exposure to cold, autopsy findings, biochemical investigation results and exclusion of other causes of death. The intention of this study was to characterize ß-hydroxybutyrate distribution in synovial fluid and assess its usefulness for the postmortem diagnosis of antemortem abnormalities in blood ß-hydroxybutyrate levels. Unenhanced CT scans, autopsies, histology, neuropathology, toxicology, and biochemistry were systematically performed. Within the limited number of subjects included in the study, the results indicate that abnormalities in antemortem ß-hydroxybutyrate blood levels, as may be observed in hypothermia fatalities, are reflected in postmortem synovial fluid values. These preliminary findings notwithstanding, synovial fluid analysis to determine ß-hydroxybutyrate is unlikely to be generally applied due to the more invasive collection technique it requires and could be limited to special cases in which biological fluids systematically collected upon autopsy are unavailable.


Asunto(s)
Ácido 3-Hidroxibutírico/análisis , Líquido Sinovial/química , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Hipotermia/sangre , Hipotermia/mortalidad , Masculino , Persona de Mediana Edad , Valores de Referencia , Adulto Joven
11.
Anal Biochem ; 455: 20-5, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24708936

RESUMEN

The discrepancy of results for the quantification of androstenedione in human serum between a radioimmunoassay (RIA) method and high performance liquid chromatography tandem-mass spectrometry (LC-MS/MS) was investigated. RIA overestimated concentrations compared to LC-MS/MS on 59 clinical samples (RIA=1.79×LC-MS/MS+0.94). RIA kit and LC-MS/MS calibrants were also determined by both methods. The RIA performed with improved accuracy on the calibrants (RIA=1.35×LC-MS/MS-0.28). Lipid, protein, electrolyte content, and pH of the two sets of calibrants were further investigated. The RIA calibrants contained little lipid material, while the LC-MS/MS calibrant material contained the same levels expected in normal serum/plasma. The pH and sex hormone binding globulin (SHBG) values were different between the RIA calibrants and the LC-MS/MS calibrant material (SHBG, 31±2 and 38±2nmol/l; pH, 8.27±0.18 and 8.66±0.03, respectively). No correlation was observed between androstenedione RIA and LC-MS/MS discrepancy and lipid or protein. LC-MS/MS sample preparation was tested for the removal of protein-bound material and recovery determined (99-108%). The corresponding RIA results overestimated androstenedione by 52-174% compared to LC-MS/MS. The results here demonstrate that LC-MS/MS is the more accurate method.


Asunto(s)
Androstenodiona/sangre , Cromatografía Líquida de Alta Presión/métodos , Radioinmunoensayo/métodos , Espectrometría de Masas en Tándem/métodos , Calibración , Humanos , Concentración de Iones de Hidrógeno , Globulina de Unión a Hormona Sexual/análisis
12.
J Forensic Sci ; 59(4): 1146-52, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24673726

RESUMEN

We herein report an autopsy case involving a 27-year-old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C-reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third-party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.


Asunto(s)
Enfermedad de Addison/complicaciones , Cetosis/etiología , 17-Hidroxicorticoesteroides/orina , Ácido 3-Hidroxibutírico/metabolismo , Adulto , Aldosterona/sangre , Proteína C-Reactiva/metabolismo , Deshidroepiandrosterona/sangre , Ayuno , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Sodio/metabolismo , Cuerpo Vítreo/metabolismo
13.
Expert Rev Gastroenterol Hepatol ; 8(5): 555-69, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24665840

RESUMEN

The better understanding of the molecular mechanisms behind gastric cancer has led to the development of new therapeutic strategies that are likely to improve patient outcomes in the near future. Recently, targeting the HER2 and the VEGF pathways with trastuzumab and ramucirumab, respectively, have been found to improve survival, while directed therapies against a number of other pathways are under clinical evaluation. These include the hepatocyte growth factor and its receptor c-MET, the insulin-like growth factor 1, the fibroblast growth factor, the mammalian target of rapamycin (mTOR), the epidermal growth factor receptor, and other pathways, as well as relevant immunotherapeutic strategies. This article reviews recent advances and future trends of these concepts for gastric cancer and adenocarcinoma of the gastroesophageal junction.


Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Diseño de Fármacos , Terapia Molecular Dirigida/tendencias , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Animales , Biomarcadores de Tumor/metabolismo , Humanos , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/secundario , Resultado del Tratamiento
14.
Int J Cancer ; 134(10): 2314-21, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24174373

RESUMEN

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non-small cell lung cancer (NSCLC) patients, treated in a first-line registry trial. For validation, 53 patients from a randomized multicentre first-line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p = 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p = 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p = 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Receptor alfa de Estrógeno/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Adhesión en Parafina/métodos , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Progesterona/genética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Tiempo
15.
J Forensic Sci ; 59(1): 161-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23980658

RESUMEN

The concentrations of 3-beta-hydroxybutyrate (3HB) in femoral blood, urine, vitreous humor as well as pericardial and cerebrospinal fluids were retrospectively examined in a series of medico-legal autopsies, which included cases of diabetic ketoacidosis, hypothermia fatalities without ethanol in blood, bodies presenting mild decompositional changes, and sudden deaths in chronic alcoholics. Similar increases in 3HB concentrations were observed in blood, vitreous, and pericardial fluid, irrespective of the cause of death, suggesting that pericardial fluid and vitreous can both be used as alternatives to blood for postmortem 3HB determination. Urine 3HB levels were higher than blood values in most cases. Cerebrospinal fluid 3HB levels were generally lower than concentrations in blood and proved to be diagnostic of underlying metabolic disturbances only when significant increases occurred.


Asunto(s)
Ácido 3-Hidroxibutírico/metabolismo , Cambios Post Mortem , Alcoholismo/metabolismo , Estudios de Casos y Controles , Muerte Súbita , Cetoacidosis Diabética/metabolismo , Femenino , Patologia Forense , Humanos , Hipotermia/metabolismo , Masculino , Persona de Mediana Edad , Pericardio/metabolismo , Estudios Retrospectivos , Cuerpo Vítreo/metabolismo
16.
J Forensic Leg Med ; 20(7): 830-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24112331

RESUMEN

The aim of this study was to identify medico-legal situations characterized by increased vitreous glucose concentrations, potentially lethal blood 3-hydroxybutyrate levels and conditions that could either incapacitate or lead to death on their own. The above was investigated in order to verify whether prolonged states of unconsciousness may play a role in precipitating diabetic ketoacidosis. Six groups of medico-legal situations (corresponding to 206 autopsy cases) were identified. Among these, three cases were characterized by pathologically increased vitreous glucose and blood 3-hydroxybutyrate levels. In one case diabetic ketoacidosis coexisted with underlying features that might have potentially incapacitated or lead to death on their own, whereas in two cases it corresponded with potentially lethal or lethal drug concentrations. The results of this study highlight the usefulness of systematically performing biochemistry in order to identify diabetic ketoacidosis-related deaths, even when autopsy and toxicology results provide apparently conclusive findings.


Asunto(s)
Sedación Consciente , Cetoacidosis Diabética/etiología , Inconsciencia , Ácido 3-Hidroxibutírico/sangre , Adulto , Atrofia , Femenino , Glucosa/análisis , Humanos , Islotes Pancreáticos/patología , Cuerpos Cetónicos/sangre , Masculino , Persona de Mediana Edad , Páncreas/patología , Trastornos Relacionados con Sustancias/complicaciones , Cuerpo Vítreo/química
17.
Pediatr Nephrol ; 28(12): 2299-306, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23949592

RESUMEN

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (ußNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR). METHODS: The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses. RESULTS: The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. ußNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission. CONCLUSIONS: Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR levels.


Asunto(s)
Proteínas de Fase Aguda/orina , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Lipocalinas/orina , Nefrosis Lipoidea/complicaciones , Síndrome Nefrótico/etiología , Proteinuria/etiología , Proteínas Proto-Oncogénicas/orina , Acetilglucosaminidasa/orina , Adolescente , Factores de Edad , alfa-Globulinas/orina , Biomarcadores/orina , Estudios de Casos y Controles , Niño , Preescolar , Creatinina/orina , Estudios Transversales , Tasa de Filtración Glomerular , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Humanos , Riñón/fisiopatología , Lipocalina 2 , Peso Molecular , Nefrosis Lipoidea/diagnóstico , Nefrosis Lipoidea/fisiopatología , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proteinuria/diagnóstico , Proteinuria/fisiopatología , Curva ROC , Recurrencia
18.
Clin Chim Acta ; 425: 104-8, 2013 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-23906797

RESUMEN

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.


Asunto(s)
Glucemia/análisis , Hipoglucemia/sangre , Sistemas de Atención de Punto/normas , Factores de Edad , Niño , Hematócrito/estadística & datos numéricos , Humanos , Hipoglucemia/diagnóstico , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
Cancer Med ; 2(3): 325-33, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23930209

RESUMEN

UNLABELLED: This study aimed at determining the recommended dose of the mammalian target of rapamycin inhibitor everolimus in combination with mitomycin C (MMC) in patients with previously treated metastatic esophagogastric cancer. In this phase I trial, patients received escalated doses of oral everolimus (5, 7.5, and 10 mg/day) in combination with intravenous MMC 5 mg/m² every 3 weeks. Endpoints were the dose-limiting toxicity (DLT), safety, and response rates. Tumor tissues were tested for HER2-status and mutations in the PTEN, PIK3CA, AKT1, CTNNB1, and E-cadherin type 1 genes. Sixteen patients (12 male, four female) with gastric/gastroesophageal junction cancer were included. All patients were previously treated with a platinum-based chemotherapy. Treatment cohorts were: 5 mg/day, three patients; 7.5 mg/day, three patients; and 10 mg/day, 10 patients. No DLTs occurred during dose escalation. Most frequent grade 3 toxicities were leukopenia (18.8%) and neutropenia (18.8%). All other grade 3 toxicities were below 10%. No grade 4 toxicities occurred. Three (18.8%) patients experienced partial responses and four patients had stable disease (SD). Antitumor activity according to Response Evaluation Criteria In Solid Tumors (RECIST)-criteria was highest in the 10 mg/day cohort. No associations between HER2-status or detected mutations and response were observed. The recommended dose of everolimus combined with MMC is 10 mg/day. Encouraging signs of antitumor activity were seen (http://www.ClinicalTrials.gov; CLINICAL TRIAL REGISTRATION NUMBER: NCT01042782).


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Neoplasias Esofágicas/patología , Everolimus , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Sirolimus/administración & dosificación , Sirolimus/efectos adversos , Sirolimus/análogos & derivados , Neoplasias Gástricas/patología , Análisis de Supervivencia
20.
Int J Legal Med ; 127(5): 943-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23722498

RESUMEN

The concentrations of 3-beta-hydroxybutyrate (3HB) in blood and two liver samples were retrospectively examined in a series of medicolegal autopsies. These cases included diabetic ketoacidosis, nondiabetic individuals presenting moderate to severe decompositional changes and nondiabetic medicolegal cases privy of decompositional changes. 3HB concentrations in liver sample homogenates correlate well with blood values in all examined groups. Additionally, decompositional changes were not associated with increases in blood and liver 3HB levels. These results suggest that 3HB can be reliably measured in liver homogenates when blood is not available at autopsy. Furthermore, they suggest that metabolic disturbances potentially leading or contributing to death may be objectified through liver 3HB determination even in decomposed bodies.


Asunto(s)
Ácido 3-Hidroxibutírico/metabolismo , Hígado/metabolismo , Cambios Post Mortem , Adolescente , Adulto , Anciano , Cetoacidosis Diabética/metabolismo , Femenino , Patologia Forense , Humanos , Modelos Lineales , Hígado/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cuerpo Vítreo/metabolismo , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA