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BACKGROUND: Brain ultrasound allows measuring the cerebral flow velocity, brain midline shift and optic nerve sheath diameter. Literature is scarce in determining the feasibility to perioperatively perform these measurements altogether and the cerebrovascular behavior in patients scheduled for elective craniotomy. METHODS: We assessed bilateral cerebral flow velocities, composite index, brain midline shift and optic nerve sheath diameter by cerebral ultrasound in patients scheduled for elective craniotomy before anesthetic induction, at extubation, and at 6 and 24 h after. The aim was to assess the feasibility of brain ultrasound in patients for elective craniotomy and to describe the changes in cerebral flow velocities, brain midline shift and optic nerve sheath diameter from baseline values at different times in the postoperative period. RESULTS: Sixteen patients were included, of these two were excluded from analysis due to an inadequate sonographic window. There were no changes throughout the study regarding cerebral flow velocity, brain midline shift nor optic nerve sheath diameter assessments. All parameters were maintained in the physiological range without significant variations during the procedure. No perioperative complications were detected. CONCLUSIONS: The results of our study show the feasibility to perform a perioperative assessment of cerebral flow velocity, brain midline shift or optic nerve sheath diameter jointly and successfully to obtain additional information of baseline cerebral hemodynamics in patients scheduled for elective craniotomy and their postoperative changes during the first 24 h. Future studies with lager samples are needed to address the efficacy of cerebral ultrasound as a monitoring tool.
Asunto(s)
Encéfalo , Ultrasonografía Doppler Transcraneal , Humanos , Estudios de Factibilidad , Velocidad del Flujo Sanguíneo , Craneotomía , Nervio Óptico/diagnóstico por imagenRESUMEN
In the Mediterranean basin, the tick species Hyalomma lusitanicum Koch stands out among other species of the Hyalomma genus due to its wide distribution, and there is great concern about its potential role as a vector and/or reservoir and its continuous expansion to new areas because of climate warming and human and other animal movements. This review aims to consolidate all the information on H. lusitanicum, including taxonomy and evolution, morphological and molecular identification, life cycle, sampling methods, rearing under laboratory conditions, ecology, hosts, geographical distribution, seasonality, vector role and control methods. The availability of adequate data is extremely relevant to the development of appropriate control strategies in areas where this tick is currently distributed as well as in new areas where it could become established in the near future.
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Ixodidae , Garrapatas , Animales , Humanos , ClimaRESUMEN
Introducción: La ecografía cerebral permite valorar las velocidades del flujo sanguíneo cerebral (VFSC), la desviación de la línea media (DLM) y el diámetro de la vaina del nervio óptico (DVNO). La literatura es escasa en determinar la viabilidad de realizar dichas medidas, de forma conjunta en el perioperatorio, en pacientes programados para craneotomía electiva. Métodos: Evaluamos las VFSC de forma bilateral con sus índices compuestos, la DLM y el DVNO por medio de ultrasonido cerebral en pacientes programados para craneotomía electiva antes de la inducción anestésica, en la extubación inmediata, a las seis y 24 horas posoperatorias. El objetivo fue evaluar la viabilidad del uso de la ecografía cerebral en pacientes sometidos a craneotomía electiva y describir los cambios de estas mediciones en diferentes momentos con respecto a los valores basales. Resultados: Fueron incluidos 16 pacientes en el estudio, de los cuales dos se excluyeron del análisis debido a una mala ventana ecográfica. No hubo cambios a lo largo del estudio con respecto a las VFSC, tampoco en la DLM o en el DVNO. Todos los parámetros se mantuvieron dentro de los rangos fisiológicos sin variaciones significativas durante el procedimiento. No hubo complicaciones perioperatorias. Conclusiones: Los resultados de nuestro trabajo muestran la factibilidad de realizar una valoración perioperatoria de las VFSC, DLM y DVNO de forma conjunta y exitosa para obtener información de la hemodinámica cerebral basal en pacientes programados para craneotomía electiva y valorar sus cambios durante las primeras 24 horas del posoperatorio. Son necesarios estudios con mayor número de pacientes para evaluar la eficacia del ultrasonido cerebral como herramienta de monitorización neurológica perioperatoria.(AU)
Background: Brain ultrasound allows measuring the cerebral flow velocity, brain midline shift and optic nerve sheath diameter. Literature is scarce in determining the feasibility to perioperatively perform these measurements altogether and the cerebrovascular behavior in patients scheduled for elective craniotomy. Methods: We assessed bilateral cerebral flow velocities, composite index, brain midline shift and optic nerve sheath diameter by cerebral ultrasound in patients scheduled for elective craniotomy before anesthetic induction, at extubation, and at 6 and 24 hours after. The aim was to assess the feasibility of brain ultrasound in patients for elective craniotomy and to describe the changes in cerebral flow velocities, brain midline shift and optic nerve sheath diameter from baseline values at different times in the postoperative period. Results: Sixteen patients were included, of these two were excluded from analysis due to an inadequate sonographic window. There were no changes throughout the study regarding cerebral flow velocity, brain midline shift nor optic nerve sheath diameter assessments. All parameters were maintained in the physiological range without significant variations during the procedure. No perioperative complications were detected. Conclusions: The results of our study show the feasibility to perform a perioperative assessment of cerebral flow velocity, brain midline shift or optic nerve sheath diameter jointly and successfully to obtain additional information of baseline cerebral hemodynamics in patients scheduled for elective craniotomy and their postoperative changes during the first 24 hours. Future studies with lager samples are needed to address the efficacy of cerebral ultrasound as a monitoring tool.(AU)
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Humanos , Neoplasias del Nervio Óptico , Craneotomía , Ultrasonografía Doppler Transcraneal , Neurocirugia , Estudios Prospectivos , Nervio ÓpticoRESUMEN
Flea infestations of wild rabbits were examined monthly in central Spain in a meso-Mediterranean area for 5 yr. A total of 1,180 wild rabbits were trapped and 7,022 fleas were collected from them. Overall, the prevalence was 74.1% with a mean flea index of 5.95 fleas per rabbit. Four flea species were identified: Spilopsyllus cuniculi (Dale, 1878) was the most abundant species (accounting for 74.3% of fleas collected) followed by Xenopsylla cunicularis (Smit, 1957), Odontopsyllus quirosi (Gil Collado, 1934), and Nosopsyllus fasciatus (Bosc, 1800) (18.9, 6.7, and 0.1%, respectively). The highest prevalence was observed in S. cuniculi (48.6%) followed by X. cunicularis, O. quirosi, and N. fasciatus (34.3, 20.0, and 0.6%, respectively). Odontopsyllus quirosi and S. cuniculi were mainly collected from autumn to spring with the peak of infestation in winter, while X. cunicularis was mainly found from spring to autumn with maximum levels of infestation during the summer months. The relevance of these findings is discussed.
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Interacciones Huésped-Parásitos , Conejos/parasitología , Estaciones del Año , Siphonaptera/fisiología , Animales , Ecosistema , Región Mediterránea , EspañaRESUMEN
Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up. PATIENTS AND METHODS: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapyâ¯+/- intravenous ZOL 4â¯mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects. RESULTS: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HRDFS â¯=â¯0.94, 95%CIâ¯=â¯0.84-1.06, pâ¯=â¯0.340; HRIDFS â¯=â¯0.91, 95%CIâ¯=â¯0.82-1.02, pâ¯=â¯0.116). However, outcomes remain improved with ZOL in postmenopausal women (HRDFS â¯=â¯0.82, 95%CIâ¯=â¯0.67-1.00; HRIDFS â¯=â¯0.78, 95%CIâ¯=â¯0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HRIDFS â¯=â¯0.75, 95%CIâ¯=â¯0.58-0.97) and OS HROS â¯=â¯0.69, 95%CIâ¯=â¯0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISHâ¯+â¯tumors. Bone metastases as a first DFS recurrence (BDFS) were reduced with ZOL (HRB-DFS â¯=â¯0.76, 95%CIâ¯=â¯0.63-0.92, pâ¯=â¯0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred. CONCLUSIONS: Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.
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Spirocerca lupi Rudolphi 1809 (Nematoda Spirocercidae) has an indirect cycle involving intermediate and paratenic hosts, having domestic or wild canids as the main definitive hosts. The most frequent pathology affecting dogs is a granulomatous tumor-like growth containing adults in the oesophagus and aorta. There are very few references about the presence of nodules in the stomach. There is scant information about the epidemiology of this disease in wild red foxes in meso-Mediterranean areas. In this work we report on the natural infection of wild red foxes by Spirocerca lupi and the damage produced in the stomach wall in an area where contact with other potential definitive hosts (canids) is very rare. From July 2015 to November 2016, 61 red foxes were sampled. 18.03% of the stomach walls examined had nodules containing Spirocerca lupi adults and eggs. The prevalence of infection was similar for young and adult groups (23.81 and 18.18%; χ2â¯=â¯0.25; dfâ¯=â¯1; Pâ¯=â¯0.6171) and it was higher in females than in males (25.81 versus 10.00%, χ2â¯=â¯2.58; dfâ¯=â¯1; Pâ¯=â¯0.1082). The red fox population in the area seems to be well established judging from their age distribution and the fact that they could be captured all year round. It would appear that in the absence of other main definitive host S. lupi population is able to survive just parasitizing red foxes. Pathologic effects of this parasite on red foxes seems to show some differences related to domestic dogs. These results also indicates as predator control programs can maintain suitable host populations with reduced level of infection.
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Reservorios de Enfermedades/veterinaria , Zorros/parasitología , Infecciones por Spirurida/veterinaria , Estómago/parasitología , Animales , Conservación de los Recursos Naturales , Reservorios de Enfermedades/parasitología , Femenino , Masculino , Región Mediterránea/epidemiología , España/epidemiología , Infecciones por Spirurida/epidemiología , Estómago/patología , Thelazioidea/aislamiento & purificaciónRESUMEN
No disponible
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Adulto , Humanos , Masculino , Lóbulo Temporal , Lóbulo Temporal/cirugía , Lóbulo Temporal , Anestesia Intravenosa/métodos , Anestesia Intravenosa , Neurocirugia/métodos , Neurocirugia/normas , Imagen por Resonancia Magnética/métodos , Espectroscopía de Mossbauer , Intubación Intratraqueal/instrumentación , Intubación Intratraqueal/métodos , Intubación IntratraquealAsunto(s)
Craneotomía , Depuradores de Gas , Complicaciones Intraoperatorias/etiología , Imagen por Resonancia Magnética , Respiración de Presión Positiva Intrínseca/etiología , Cirugía Asistida por Computador , Anestesia Intravenosa , Neoplasias Encefálicas/cirugía , Falla de Equipo , Humanos , Hipertensión Intracraneal/etiología , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Lóbulo Temporal/cirugíaRESUMEN
Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and ß, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin.
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Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Dioxoles/farmacología , Liposarcoma Mixoide/genética , Liposarcoma Mixoide/metabolismo , Tetrahidroisoquinolinas/farmacología , Apoptosis , Proteína C-Reactiva/genética , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/genética , Metilación de ADN , Metilasas de Modificación del ADN/deficiencia , Metilasas de Modificación del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Reparación del ADN , Enzimas Reparadoras del ADN/deficiencia , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Resistencia a Antineoplásicos , Fibronectinas/genética , Humanos , Liposarcoma Mixoide/tratamiento farmacológico , Liposarcoma Mixoide/patología , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Regiones Promotoras Genéticas , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismo , Componente Amiloide P Sérico/genética , Transducción de Señal , Temozolomida , Trabectedina , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Rayos UltravioletaRESUMEN
BACKGROUND: To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation. PATIENTS AND METHODS: Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point. RESULTS: Three of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types. CONCLUSION: Trabectedin 1.5 mg/m(2) given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML.
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Antineoplásicos Alquilantes/uso terapéutico , Dioxoles/uso terapéutico , Liposarcoma Mixoide/tratamiento farmacológico , Terapia Neoadyuvante , Tetrahidroisoquinolinas/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trabectedina , Adulto JovenRESUMEN
The ditopic ligand PyPzOAPz (N-[(Z)-amino(pyrazin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid) was synthesized by in situ condensation of methyl imino pyrazine-2-carboxylate with 5-methyl-1-(2-pyridyl) pyrazole-3-carbohydrazide. In this work we have also used two of our earlier ligands PzCAP (5-methyl-N-[(1E)-1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazonic acid) (Dalton Trans., 2009, 8215) and PzOAP (N-[(Z)-amino(pyridin-2-yl)methylidene]-5-methyl-1H-pyrazole-3-carbohydrazonic acid) (Dalton Trans., 2007, 1229). These ligands PzCAP, PzOAP and PyPzOAPz were made to react with Mn(ClO(4))(2)·6H(2)O to produce three pentanuclear Mn(II) clusters [Mn(5)(PzCAP)(6)](ClO(4))(4) (1), [Mn(5)(PzOAP)(6)](ClO(4))(4) (2) and [Mn(5)(PyPzOAPz)(6)](ClO(4))(4) (3). These complexes have been characterized by X-ray structural analyses and variable temperature magnetic susceptibility measurements. All complexes have a pentanuclear core with trigonal bipyramidal arrangement of Mn(II) atoms, where, the axial metal centers have a N(3)O(3) chromophore and the equatorial centers have N(4)O(2) with an octahedral arrangement. These Mn(5)(II) clusters 1, 2 and 3 show the presence of antiferromagnetic coupling within the pentanuclear manganese(II) core (J = -2.95, -3.19 and -3.00 cm(-1) respectively). Density functional theory calculations and continuous shape measurement (CShM) studies have been performed on these complexes to provide a qualitative theoretical interpretation of the antiferromagnetic behaviour shown by them. The pentanuclear Mn(II) cluster (1) on reaction with Cu(NO(3))(2)·6H(2)O in 1:1 mole proportion in CH(3)OH:H(2)O (60 : 40) forms a homoleptic [2 × 2] tetranuclear Cu(4)(II) grid [Cu(4)(PzCAP)(4)(NO(3))(2)](NO(3))(2)·8H(2)O (4). The same Cu(4)(II) grid is also obtained from a direct reaction between the ditopic ligand PzCAP with Cu(NO(3))(2)·6H(2)O in 1:1 mole proportion. This conversion of a cluster to a grid is a novel observation.
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Complejos de Coordinación/síntesis química , Hidrazinas/química , Magnetismo , Manganeso/química , Modelos Moleculares , Pirazoles/química , Complejos de Coordinación/química , Cristalografía por Rayos X , Hidrazinas/síntesis química , Ligandos , Imanes , Conformación Molecular , Pirazoles/síntesis químicaRESUMEN
Objetivo: Transmitir la experiencia con el uso de la mascarilla laríngea Proseal (MLP) en el manejo de la vía aérea de los pacientes sometidos a cirugía de derivación ventrículo peritoneal, en cuanto a su utilidad, eficacia y seguridad. Pacientes y métodos: Revisamos retrospectivamente las historias de todos los pacientes sometidos a derivación ventrículo peritoneal y ventilados con MLP entre enero del 2006 y octubre del 2009. Registramos las características demográficas de los pacientes, valoración de la vía aérea, tipo de anestesia, calidad de ventilación y complicaciones perioperatorias. Resultados: Se incluyeron 43 pacientes, 8 (18,6%) cumplían algún criterio de vía aérea difícil (VAD). La inserción de la MLP fue posible en todos los pacientes. La ventilación fue óptima en 39 pacientes (91%), manteniendo valores entre 35-40 mmHg de CO2 telespiratorio y presiones de vía aérea por debajo de 25 cmH2O durante todo el procedimiento. Tres pacientes (7%) presentaron fugas en la vía aérea al ser colocados en la posición quirúrgica cervical lateral forzada y precisaron intubación orotraqueal para iniciar la cirugía. El tiempo quirúrgico promedio fue de 53 minutos. La educción ocurrió sin incidentes en todos los casos. Conclusiones: La MLP es útil en el manejo de la vía aérea de los pacientes intervenidos de derivación ventriculoperitoneal, aunque debido a la posición forzada del cuello, puede ser necesario ajustar la colocación de la mascarilla, y en algunos casos la intubación orotraqueal. Como en otros usos avanzados se requiere experiencia en su uso y tener disponible el material de VAD(AU)
Objective: To describe the use, utility, safety, and effectiveness of the Proseal laryngeal mask for airway management in patients undergoing ventriculoperitoneal shunting. Patients and methods: We retrospectively reviewed the records of all patients in whom the Proseal laryngeal mask was used during ventriculoperitoneal shunting between January 2006 and October 2009. Patient demographic characteristics, airway assessments, type of anesthesia, quality of ventilation, and perioperative complications were recorded. Results: Of the 43 patients included, 8 (18.6%) had at least 1 difficult airway criterion. We were able to insert the Proseal laryngeal mask in all patients. Ventilation was optimal in 39 (91%) patients, with maintenance of end-expiratory carbon dioxide pressures between 35 and 40 mm Hg and airway pressures above 25 cm H2O throughout the procedures. Air leaks developed in 3 cases (7%) when the patient was placed in a lateralcervical position for surgery; these patients required orotracheal intubation before surgery could begin. Mean duration of surgery was 53 minutes. Awakening occurred without incident in all cases. Conclusions: The Proseal laryngeal mask is useful for airway management in patients undergoing ventriculoperitoneal shunting. Due to the forced position of the neck, however, it may be necessary to reposition the mask or even proceed to orotracheal intubation in some cases. As is the case for other advanced uses, experience with the device is necessary. Material for managing a difficult airway should be on hand(AU)
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Humanos , Masculino , Femenino , Máscaras , Anestesia/clasificación , Anestesia , Intubación Intratraqueal/métodos , Intubación/métodos , Máscaras/tendencias , Eficacia/métodos , Evaluación de Eficacia-Efectividad de Intervenciones , Estudios RetrospectivosRESUMEN
OBJECTIVE: To describe the use, utility, safety, and effectiveness of the Proseal laryngeal mask for airway management in patients undergoing ventriculoperitonea shunting. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients in whom the Proseal laryngeal mask was used during ventriculoperitoneal shunting between January 2006 and October 2009. Patient demographic characteristics, airway assessments, type of anesthesia, quality of ventilation, and perioperative complications were recorded. RESULTS: Of the 43 patients included, 8 (18.6%) had at least 1 difficult airway criterion. We were able to insert the Proseal laryngeal mask in all patients. Ventilation was optimal in 39 (91%) patients, with maintenance of end-expiratory carbon dioxide pressures between 35 and 40 mm Hg and airway pressures above 25 cm H2O throughout the procedures. Air leaks developed in 3 cases (7%) when the patient was placed in a lateral-cervical position for surgery; these patients required orotracheal intubation before surgery could begin. Mean duration of surgery was 53 minutes. Awakening occurred without incident in all cases. CONCLUSIONS: The Proseal laryngeal mask is useful for airway management in patients undergoing ventriculoperitoneal shunting. Due to the forced position of the neck, however, it may be necessary to reposition the mask or even proceed to orotracheal intubation in some cases. As is the case for other advanced uses, experience with the device is necessary. Material for managing a difficult airway should be on hand.
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Máscaras Laríngeas , Derivación Ventriculoperitoneal , Manejo de la Vía Aérea , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
AIM: Trabectedin sensitivity is increased in cells with functional nucleotide excision DNA repair, whereas efficient homologous recombination repair leads to resistance. On this basis, a retrospective study of mRNA expression of BRCA1 (breast cancer susceptibility 1 gene), XPG (Xeroderma pigmentosum group G gene) and ERCC1 (excision-repair cross complementing group 1 gene) in tumour samples from sarcoma patients treated with trabectedin was conducted, to correlate DNA repair profiles with patient outcome. MATERIALS AND METHODS: Quantification of expression in paraffin embedded tumour samples from 245 patients with advanced sarcomas was performed by qRT-PCR (quantitative real-time polymerase chain reaction). Median values were used as cut-off to define low/high mRNA expression. RESULTS: Low BRCA1 mRNA expression in tumour samples correlated with statistically significant better response to trabectedin. In contrast to other DNA interacting agents, high expression of XPG was significantly correlated with increased response to the drug and high ERCC1 or XPD (Xeroderma pigmentosum group D gene) expression did not have a detrimental impact. A composite signature including low BRCA1 and high ERCC1 and/or XPG identifies a highly sensitive population of sarcomas with significantly improved treatment outcome. DISCUSSION: This retrospective study indicates that the DNA repair profile predicts improved outcomes in advanced sarcoma patients when treated with trabectedin. This clinical utility of this signature should be evaluated in prospective enriching studies in sarcoma and other malignancies for patients sensitive to trabectedin.
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Antineoplásicos Alquilantes/uso terapéutico , Reparación del ADN , Dioxoles/uso terapéutico , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Tetrahidroisoquinolinas/uso terapéutico , Proteína BRCA1/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas Nucleares/genética , ARN Mensajero/metabolismo , Recombinación Genética , Estudios Retrospectivos , Trabectedina , Factores de Transcripción/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Trabectedin has been approved in Europe as second-line therapy for advanced soft tissue sarcomas. A previous analysis showed that myxoid liposarcomas (MLS) are particularly sensitive to the drug. We report on the long-term efficacy of trabectedin in a subgroup of that series. METHODS: Since September 2002, 32 advanced pretreated MLS patients received trabectedin at our center. Data were reviewed focusing on their long-term outcome. RESULTS: Trabectedin was given as a 24-h continuous infusion every 21 days. A total of 376 and a median of 12 courses per patient (range 2-26; interquartiles range (IQR) 8-15) were delivered. Response rate per RECIST was 50% [95% confidence interval (CI) 32% to 68%], median progression-free survival (PFS) was 17 months (95% CI 13.5-30.1) and median overall survival is still not reached. In 10 patients, therapy was stopped in the absence of any evident disease, mostly after complete surgery of residual lesions. In these 10 patients, at a median follow-up of 25 months, PFS was 28.1 months (95% CI 25.6-36.4) from treatment start. DISCUSSION: These data indicate that the high response rate of MLS to trabectedin translates into prolonged PFS. Surgery of residual metastatic disease is already used quite extensively in metastatic MLS. Trabectedin may give further significance to this kind of surgery.
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Antineoplásicos Alquilantes/administración & dosificación , Dioxoles/administración & dosificación , Liposarcoma Mixoide/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Tetrahidroisoquinolinas/administración & dosificación , Adulto , Anciano , Antineoplásicos Alquilantes/efectos adversos , Dioxoles/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tetrahidroisoquinolinas/efectos adversos , Muslo , TrabectedinaRESUMEN
OBJECTIVE: The aim of this study was to describe monitoring, anesthetic management, and risk factors for complications in neuroendoscopic surgery. PATIENTS AND METHODS: Patients who underwent neuroendoscopy between 1994 and 2003 under general anesthesia, with monitoring of intracranial pressure from inside the neuroendoscope, were studied retrospectively. In some patients, the blood flow rate in the middle cerebral artery was monitored using transcranial Doppler ultrasound. Information was collected related to surgical procedure and the development of complications. RESULTS: Of 101 patients included in the study, transcranial Doppler ultrasound images were available for 20. In 75 patients neuroendoscopic intracranial pressure exceeded 20 mm Hg. Forty-five percent of the patients with available transcranial Doppler ultrasound images showed episodes of reduced diastolic flow rate in the middle cerebral artery during ventricular irrigation. Hemodynamic instability was associated with higher neuroendoscopic intracranial pressures (P < .05). An increase of more than 30 mm Hg in neuroendoscopic intracranial pressure was associated with more postoperative complications, the most common of which was delayed awakening. Procedures that were more complicated than a simple ventriculostomy were performed in 58% of the cases. Mean (SD) neuroendoscopic intracranial pressures in such cases were higher (50.5 [30.9] mm Hg vs 31.8 [25.1 mm Hg] in the simpler procedures) and the postoperative complication rate was higher (P = .003). CONCLUSIONS: Neuroendoscopic surgery can causes increases in neuroendoscopic intracranial pressure that are associated with disturbances in cerebral blood flow and complications. This situation demonstrates the importance of monitoring intracranial pressure and cerebral blood flow.
Asunto(s)
Circulación Cerebrovascular , Retraso en el Despertar Posanestésico/etiología , Hipertensión Intracraneal/diagnóstico , Presión Intracraneal , Complicaciones Intraoperatorias/diagnóstico , Manometría/instrumentación , Monitoreo Intraoperatorio/métodos , Neuroendoscopios , Neuroendoscopía/efectos adversos , Procedimientos Neuroquirúrgicos/efectos adversos , Adolescente , Adulto , Anciano , Anestesia General , Velocidad del Flujo Sanguíneo , Niño , Preescolar , Retraso en el Despertar Posanestésico/prevención & control , Diseño de Equipo , Femenino , Humanos , Lactante , Hipertensión Intracraneal/diagnóstico por imagen , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/prevención & control , Complicaciones Intraoperatorias/diagnóstico por imagen , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Masculino , Manometría/métodos , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Procedimientos Neuroquirúrgicos/instrumentación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Irrigación Terapéutica/efectos adversos , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
OBJETIVOS: El objetivo del estudio es describir la monitorización específica, el manejo anestésico, y los factores predictivos de complicaciones en la cirugía neuroendoscópica.PACIENTES Y MÉTODOS: Estudiamos retrospectivamente a los pacientes sometidos a neuroendoscopia con anestesiageneral, con monitorización del valor de la presiónen el interior del neuroendoscopio, desde 1994 hasta2003. En algunos casos se monitorizó además la velocidaddel flujo sanguíneo de la arteria cerebral mediamediante doppler transcraneal. Se registró el procedimientoquirúrgico y la aparición de complicaciones.RESULTADOS: Se incluyeron 101 pacientes, 20 conregistro de doppler transcraneal. En 75 pacientes, la presiónen el interior del neuroendoscopio presentó valoressuperiores a 20 mmHg. El 45% de los pacientes con dopplertranscraneal presentaron episodios de disminuciónde velocidad diastólica de la arteria cerebral mediadurante la irrigación ventricular. La aparición de alteracioneshemodinámicas se asoció a valores más elevadosde presión en el interior del neuroendoscopio (p < 0,05).El aumento de presión en el interior del neuroendoscopiomayor de 30 mmHg, se asoció con el aumento decomplicaciones postoperatorias, siendo la más frecuenteel retraso en el despertar. En el 58% de los casos se realizaron procedimientos quirúrgicos más complejos queuna ventriculostomía simple. En estos casos, los valores de presión en el interior del neuroendoscopio fueron máselevados comparado con las ventriculostomías simples(50,5 ± 30,9 frente a 31,8 ± 25,1 mmHg; p = 0,001) y se asociaron a una aparición de más complicaciones en elpostoperatorio (p=0,003). CONCLUSIONES: La cirugía neuroendoscópica puede provocar aumentos de presión en el interior del neuroendoscopio que se asocia a alteraciones del flujo sanguíneocerebral y la aparición de complicaciones, lo que apoya la importancia de la monitorización de la presión intracraneal y el flujo sanguíneo cerebral(AU)
OBJECTIVE: The aim of this study was to describemonitoring, anesthetic management, and risk factors forcomplications in neuroendoscopic surgery.PATIENTS AND METHODS: Patients who underwentneuroendoscopy between 1994 and 2003 under generalanesthesia, with monitoring of intracranial pressurefrom inside the neuroendoscope, were studiedretrospectively. In some patients, the blood flow rate inthe middle cerebral artery was monitored usingtranscranial Doppler ultrasound. Information wascollected related to surgical procedure and thedevelopment of complications.RESULTS: Of 101 patients included in the study,transcranial Doppler ultrasound images were availablefor 20. In 75 patients neuroendoscopic intracranialpressure exceeded 20 mm Hg. Forty-five percent of thepatients with available transcranial Doppler ultrasoundimages showed episodes of reduced diastolic flow rate inthe middle cerebral artery during ventricular irrigation.Hemodynamic instability was associated with higherneuroendoscopic intracranial pressures (P<.05). Anincrease of more than 30 mm Hg in neuroendoscopicintracranial pressure was associated with morepostoperative complications, the most common of whichwas delayed awakening. Procedures that were morecomplicated than a simple ventriculostomy wereperformed in 58% of the cases. Mean (SD)neuroendoscopic intracranial pressures in such caseswere higher (50.5 [30.9] mm Hg vs 31.8 [25.1 mm Hg] inthe simpler procedures) and the postoperativecomplication rate was higher (P=.003).CONCLUSIONS: Neuroendoscopic surgery can causesincreases in neuroendoscopic intracranial pressure thatare associated with disturbances in cerebral blood flowand complications. This situation demonstrates theimportance of monitoring intracranial pressure andcerebral blood flow(AU)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Anciano , Adulto , Preescolar , Niño , Lactante , Persona de Mediana Edad , Anestesia General , Hipertensión Intracraneal/diagnóstico , Presión Intracraneal , Complicaciones Intraoperatorias/diagnóstico , Irrigación Terapéutica/efectos adversos , Manometría/instrumentación , Procedimientos Neuroquirúrgicos/efectos adversos , Neuroendoscopios , Neuroendoscopía/efectos adversos , Velocidad del Flujo Sanguíneo , Diseño de Equipo/métodos , Hipertensión Intracraneal , Complicaciones Intraoperatorias , Procedimientos Neuroquirúrgicos/instrumentación , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Ultrasonografía Doppler Transcraneal , Arteria Cerebral Media/fisiopatología , Arteria Cerebral MediaRESUMEN
OBJECTIVE: There is little available information regarding contamination of perineural catheters. Incidence ranges from 5% to 57%, depending on the location of the catheter. The objective of this prospective study was to evaluate the incidence and predisposing factors of bacterial contamination of these catheters. PATIENTS AND METHODS: The study included 47 patients who had an epidural (24 patients) or perineural (23 patients) catheter inserted for a minimum of 48 hours. We recorded details of the patients' characteristics, difficulty of insertion and duration of placement of the catheter, antibiotic treatment received, and signs of local or systemic infection immediately after surgery. When the catheters were removed, cultures were prepared using the Maki method. A descriptive analysis was performed and the frequency of contamination was determined using various parameters. RESULTS: The incidence of contamination was 28% (13 patients): 5/24 (21%) in epidural catheters, 6/17 (35%) in femoral catheters, and 2/6 (33%) in brachial and sciatic plexus catheters. Colonization was not influenced by the patients' characteristics, technical difficulties in placing the catheter, prophylactic antibiotic treatment, or the characteristics of the infusion administered. None of the patients presented clinical signs of infection. The most commonly isolated microorganism was Staphylococcus epidermidis, found in 10 patients (69% of the colonized catheters). CONCLUSIONS: Although infection of perineural catheters is exceptional when they are placed for 2 or more days, contamination is very common. Epidemiological studies are required to evaluate the variables involved.
Asunto(s)
Analgesia Epidural/instrumentación , Bacterias/aislamiento & purificación , Plexo Braquial , Cateterismo , Contaminación de Equipos/estadística & datos numéricos , Plexo Lumbosacro , Dolor Postoperatorio/tratamiento farmacológico , Profilaxis Antibiótica , Bacteriemia/prevención & control , Humanos , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , España/epidemiología , Staphylococcus epidermidis/aislamiento & purificación , Factores de TiempoRESUMEN
OBJETIVOS: Existen pocos datos acerca de la contaminaciónde catéteres dispuestos en posición perineural. Suincidencia se sitúa entre el 5% y el 57% en base a lalocalización del catéter. Planteamos este estudio prospectivo para evaluar la incidencia y factores predisponentes de la contaminación bacteriana de estos.PACIENTES Y MÉTODOS: Se incluyeron 47 pacientes aquienes se les colocó un catéter epidural (24 pacientes) o perineural (23 pacientes) por un periodo mínimo de 48horas. Se recogieron las características de los pacientes, dificultad de inserción y tiempo de colocación del catéter, antibioticoterapia recibida y signos de infección local o sistémica en el postoperatorio inmediato. Tras la retirada delcatéter se realizó el cultivo mediante el método de Maki. Se realizó un análisis descriptivo y se determinó la frecuencia de contaminación en función de distintos parámetros.RESULTADOS: La incidencia de contaminación fue de 13pacientes (28%): 5/24 (21%) en epidurales, 6/17 (35%) enlos femorales y 2/6 (33%) en los plexos braquial y ciático. La colonización no se vio influenciada por las características de los pacientes, las dificultades técnicas en colocación del catéter, la antibioticoterapia profiláctica, ni por las características de la infusión administrada. Ningúnpaciente presentó clínica sugestiva de infección. El microorganismo más frecuentemente aislado fue Staphylococcus epidermidis en 10 pacientes (69% de los colonizados).CONCLUSIONES: Si bien la infección de los catéteresperineurales es excepcional cuando se mantienen durantedos o más días, su contaminación es muy frecuente. Serequieren estudios epidemiológicos amplios para evaluarlas variables implicadas
OBJECTIVE: There is little available informationregarding contamination of perineural catheters. Incidence ranges from 5% to 57%, depending on the location of the catheter. The objective of this prospective study was to evaluate the incidence and predisposing factors of bacterial contamination of these catheters.PATIENTS AND METHODS: The study included 47 patientswho had an epidural (24 patients) or perineural (23patients) catheter inserted for a minimum of 48 hours. Werecorded details of the patients characteristics, difficulty of insertion and duration of placement of the catheter, antibiotic treatment received, and signs of local or systemic infection immediately after surgery. When the catheters were removed, cultures were prepared using the Maki method. A descriptive analysis was performed and the frequency of contamination was determined using various parameters.RESULTS: The incidence of contamination was 28% (13patients): 5/24 (21%) in epidural catheters, 6/17 (35%) in femoral catheters, and 2/6 (33%) in brachial and sciatic plexus catheters. Colonization was not influenced by the patients characteristics, technical difficulties in placing the catheter, prophylactic antibiotic treatment, or the characteristics of the infusion administered. None of the patients presented clinical signs of infection. The most commonly isolated microorganism was Staphylococcus epidermidis, found in 10 patients (69% of the colonized catheters).CONCLUSIONS: Although infection of perineural cathetersis exceptional when they are placed for 2 or more days,contamination is very common. Epidemiological studies arerequired to evaluate the variables involved
Asunto(s)
Humanos , Dolor Postoperatorio/tratamiento farmacológico , Analgesia Epidural/métodos , Cateterismo/métodos , Catéteres de Permanencia/microbiología , Infecciones/epidemiologíaRESUMEN
The checkpoint kinase proteins Mec1 and Rad53 are required in the budding yeast, Saccharomyces cerevisiae, to maintain cell viability in the presence of drugs causing damage to DNA or arrest of DNA replication forks. It is thought that they act by inhibiting cell cycle progression, allowing time for DNA repair to take place. Mec1 and Rad53 also slow S phase progression in response to DNA alkylation, although the mechanism for this and its relative importance in protecting cells from DNA damage have not been determined. Here we show that the DNA-alkylating agent methyl methanesulphonate (MMS) profoundly reduces the rate of DNA replication fork progression; however, this moderation does not require Rad53 or Mec1. The accelerated S phase in checkpoint mutants, therefore, is primarily a consequence of inappropriate initiation events. Wild-type cells ultimately complete DNA replication in the presence of MMS. In contrast, replication forks in checkpoint mutants collapse irreversibly at high rates. Moreover, the cytotoxicity of MMS in checkpoint mutants occurs specifically when cells are allowed to enter S phase with DNA damage. Thus, preventing damage-induced DNA replication fork catastrophe seems to be a primary mechanism by which checkpoints preserve viability in the face of DNA alkylation.