RESUMEN
PURPOSE: The study aimed to assess whether engagement in a memory training programme and performing internet brain training exercises improve memory function in people with temporal lobe epilepsy (TLE). METHODS: Seventy-seven people with TLE, complaining of memory difficulties, completed the study. Participants ranged in age from 19 to 67 years and 40 had left TLE. Participants were randomised to one of four conditions; Group 1: traditional memory training, Group 2: Lumosity, an on-line cognitive training programme, Group 3: traditional memory training and Lumosity, and Group 4: no training. Memory efficiency and mood were assessed at baseline and three months later. RESULTS: Group analyses indicated improved verbal recall after training (p<0.001) and improved subjective ratings (p<0.007). More participants reported a lessening of the memory burden (p<0.007) after training; differences were significant between Groups 1 and 3 compared to Group 4. Lumosity use was not associated with changes in the memory outcome measures but there was a relationship with depression ratings and the number of memory games played (p<0.01). Conventional memory training, IQ, and post-surgical status were associated with positive memory outcomes. CONCLUSIONS: The study indicates traditional memory rehabilitation techniques can help reduce the burden of memory impairment in TLE. There was no evidence that Lumosity the on-line cognitive training programme had specific advantages. Positive change was not universal and larger studies will be required to explore factors associated with successful outcomes.
Asunto(s)
Epilepsia del Lóbulo Temporal/rehabilitación , Aprendizaje , Trastornos de la Memoria/rehabilitación , Rehabilitación Neurológica/métodos , Evaluación de Resultado en la Atención de Salud , Adulto , Anciano , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Internet , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Functional variants in the interleukin-6 receptor gene (IL6R) are associated with asthma risk. We hypothesized that genes co-expressed with IL6R might also be regulated by genetic polymorphisms that are associated with asthma risk. The aim of this study was to identify such genes. METHODS: To identify genes whose expression was correlated with that of IL6R, we analyzed gene expression levels generated for 373 human lymphoblastoid cell lines by the Geuvadis consortium and for 38 hematopoietic cell types by the Differentiation Map Portal (DMAP) project. Genes correlated with IL6R were then screened for nearby single nucleotide polymorphisms (SNPs) that were significantly associated with both variation in gene expression levels (eSNPs) and asthma risk. RESULTS: We identified 90 genes with expression levels correlated with those of IL6R and that also had a nearby eSNP associated with disease risk in a published asthma GWAS (N = 20 776). For 16 (18%) genes, the association between the eSNP and asthma risk replicated with the same direction of effect in a further independent published asthma GWAS (N = 27 378). Among the top replicated associations (FDR < 0.05) were eSNPs for four known (IL18R1, IL18RAP, BCL6, and STAT6) and one putative novel asthma risk gene, stomatin-like protein 2 (STOML2). The expression of STOML2 was negatively correlated with IL6R, while eSNPs that increased the expression of STOML2 were associated with an increased asthma risk. CONCLUSION: The expression of STOML2, a gene that plays a key role in mitochondrial function and T-cell activation, is associated with both IL-6 signaling and asthma risk.
Asunto(s)
Asma/genética , Proteínas Sanguíneas/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/genética , Receptores de Interleucina-6/genética , Alelos , Asma/metabolismo , Línea Celular , Mapeo Cromosómico , Análisis por Conglomerados , Biología Computacional/métodos , Expresión Génica , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/metabolismo , Transducción de SeñalRESUMEN
PURPOSE: To examine the cognitive risks of temporal lobe surgery in patients aged 50 years and older. METHODS: We analysed data from 55 patients who underwent temporal lobe surgery (26 left-sided:29 right sided) from 1988 to 2012 at our centre. Pre-surgical and one year post-operative memory and naming capacity were compared to data obtained from two younger cohorts; 185 aged 18-30 and 220 aged 31-49. RESULTS: Pre-operative memory impairments were most marked for the oldest cohort and were associated with a longer duration of epilepsy. Naming capacity improved with age and better performance was associated with a later age at epilepsy onset. Post-operative declines were largest in older patients, achieving statistical significance for verbal memory, naming and subjective ratings. Left temporal lobe resections carried the greatest risk of memory and naming decline. Cognitive outcomes were unrelated to seizure outcome, VIQ or mood. CONCLUSION: Our findings indicate the cognitive risks of TLE surgery are greater for older patients. Cognitive outcomes need to be considered when assessing the efficacy of epilepsy surgery in older cohorts and pre-operative performance levels need to be taken into account.
Asunto(s)
Cognición , Epilepsia del Lóbulo Temporal/psicología , Epilepsia del Lóbulo Temporal/cirugía , Memoria , Procedimientos Neuroquirúrgicos/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Humanos , Masculino , Trastornos de la Memoria/fisiopatología , Persona de Mediana Edad , Pruebas Psicológicas , Riesgo , Factores de Riesgo , Percepción del Habla , Resultado del Tratamiento , Adulto JovenRESUMEN
AIMS: In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. METHODS: We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. RESULTS: Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. CONCLUSION: Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Memoria/fisiología , Adulto , Edad de Inicio , Epilepsia del Lóbulo Temporal/etiología , Epilepsia del Lóbulo Temporal/patología , Cara , Femenino , Lateralidad Funcional , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa , Lectura , Esclerosis , Convulsiones/etiología , Convulsiones/patología , Convulsiones/fisiopatología , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. METHODS: 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuo-spatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. FINDINGS: Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. CONCLUSIONS: Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/psicología , Giro del Cíngulo/fisiopatología , Trastornos del Humor/fisiopatología , Trastornos del Humor/psicología , Adolescente , Adulto , Anisotropía , Estudios de Casos y Controles , Corteza Cerebral/fisiopatología , Depresión/complicaciones , Depresión/patología , Depresión/fisiopatología , Imagen de Difusión Tensora , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/patología , Femenino , Neuroimagen Funcional , Sustancia Gris/patología , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Trastornos del Humor/complicaciones , Trastornos del Humor/patología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Escalas de Valoración Psiquiátrica , Desempeño Psicomotor/fisiología , Adulto JovenRESUMEN
BACKGROUND: The 6-min walk distance (6MWD) and incremental shuttle walk distance (ISWD) are clinically meaningful measures of exercise capacity in people with non-cystic fibrosis (CF) bronchiectasis, but the change in walking distance which constitutes clinical benefit is undefined. This study aimed to determine the minimal important difference for the 6MWD and ISWD in non-CF bronchiectasis. METHODS: Thirty-seven participants with mean FEV1 70% predicted completed both field walking tests before and after an 8-week exercise program. The minimal important difference was calculated using a distribution-based and anchor-based method, with the global rating of change scale used. RESULTS: The mean change in 6MWD in participants who reported themselves to be unchanged was 10 m, compared to 36 m (small change) and 45 m (substantial change) (p = 0.01). For the ISWD, the mean change in participants who reported themselves to be unchanged was 33 m, compared to 54 m (small change) and 73 m (substantial change) (p = 0.04). The anchor-based method defined the minimal important difference for 6MWD as 24.5 m (AUC 0.76, 95% CI 0.61-0.91) and for ISWD as 35 m (AUC 0.88, 95% CI 0.73-0.99), based on participant's global rating of change. The distribution-based method indicated a value of 22.3 m for the 6MWD and 37 m for the ISWD. There was excellent agreement between the two methods for the 6MWD (kappa = 0.91) and the ISWD (kappa = 0.92). CONCLUSIONS: Small changes in 6MWD and ISWD may represent clinically important benefits in people with non-CF bronchiectasis. These data are likely to assist in the interpretation of change in exercise capacity following intervention.
Asunto(s)
Bronquiectasia/rehabilitación , Prueba de Esfuerzo/métodos , Terapia por Ejercicio/métodos , Caminata , Anciano , Anciano de 80 o más Años , Bronquiectasia/etiología , Bronquiectasia/fisiopatología , Fibrosis Quística/complicaciones , Tolerancia al Ejercicio/fisiología , Volumen Espiratorio Forzado/fisiología , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND: Neuronal networks involved in seizure generation, maintenance and spread of epileptic activity comprise cortico-subcortical circuits. Although epileptic foci vary in location across focal epilepsy syndromes, there is evidence for common structures in the epileptogenic networks. We recently reported evidence from functional neuroimaging for a unique area in the piriform cortex, common to focal epilepsies in humans, which might play a role in modulating seizure activity. In this study, we aimed to identify common areas of structural abnormalities in patients with frontal lobe epilepsy (FLE). METHODS: T1-weighted MRI scans of 43 FLE patients and 25 healthy controls were analysed using voxel based morphometry. Differences in regional grey matter volume were examined across the whole brain, and correlated with age at epilepsy onset, duration and frequency of seizures. RESULTS: We detected areas of increased grey matter volume in the piriform cortex, amygdala and parahippocampal gyrus bilaterally, as well as left mid temporal gyrus of patients relative to controls, which did not correlate with any of the clinical variables tested. No common areas of atrophy were detected across the FLE group. CONCLUSIONS: Structural abnormalities within the piriform cortex and adjacent structures of patients with FLE provide further evidence for the involvement of this area in the epileptogenic network of focal epilepsies. Lack of correlation with duration or age of onset of epilepsy suggests that this area of abnormality is not a consequence of seizure activity.
Asunto(s)
Epilepsia del Lóbulo Frontal/patología , Corteza Piriforme/patología , Lóbulo Temporal/patología , Adolescente , Adulto , Edad de Inicio , Amígdala del Cerebelo/patología , Epilepsia del Lóbulo Frontal/fisiopatología , Femenino , Lateralidad Funcional , Sustancia Gris/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fibras Nerviosas Amielínicas/patología , Tamaño de los Órganos , Giro Parahipocampal/patología , Adulto JovenRESUMEN
Working memory is a critical building block for almost all cognitive tasks, and impairment can cause significant disruption to daily life routines. We investigated the functional connectivity (FC) of the visuo-spatial working memory network in temporal lobe epilepsy and its relationship to the underlying white matter tracts emanating from the hippocampus. Fifty-two patients with unilateral hippocampal sclerosis (HS) (30 left) and 30 healthy controls underwent working memory functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). Six seed regions were identified for FC analysis; 4 within a task-positive network (left and right middle frontal gyri and superior parietal lobes), and 2 within a task-negative network (left and right hippocampi). FC maps were created by extracting the time-series of the fMRI signal in each region in each subject and were used as regressors of interest for additional GLM fMRI analyses. Structural connectivity (SC) corresponding to areas to which the left and right hippocampi were connected was determined using tractography, and a mean FA for each hippocampal SC map was calculated. Both left and right HS groups showed atypical FC between task-positive and task-negative networks compared to controls. This was characterised by co-activation of the task-positive superior parietal lobe ipsilateral to the typically task-negative sclerosed hippocampus. Correlational analysis revealed stronger FC between superior parietal lobe and ipsilateral hippocampus, was associated with worse performance in each patient group. The SC of the hippocampus was associated with the intra-hemispheric FC of the superior parietal lobe, in that greater SC was associated with weaker parieto-frontal FC. The findings suggest that the segregation of the task-positive and task-negative FC networks supporting working memory in TLE is disrupted, and is associated with abnormal structural connectivity of the sclerosed hippocampus. Co-activation of parieto-temporal regions was associated with poorer working memory and this may be associated with working memory dysfunction in TLE.
RESUMEN
BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480â889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
Asunto(s)
Asma/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Australia , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Humanos , Metaanálisis como Asunto , Índice de Severidad de la EnfermedadRESUMEN
It has traditionally been held that the hippocampus is not part of the neural substrate of working memory (WM), and that WM is preserved in Temporal Lobe Epilepsy (TLE). Recent imaging and neuropsychological data suggest this view may need revision. The aim of this study was to investigate the neural correlates of WM in TLE using functional MRI (fMRI). We used a visuo-spatial 'n-back' paradigm to compare WM network activity in 38 unilateral hippocampal sclerosis (HS) patients (19 left) and 15 healthy controls. WM performance was impaired in both left and right HS groups compared to controls. The TLE groups showed reduced right superior parietal lobe activity during single- and multiple-item WM. No significant hippocampal activation was found during the active task in any group, but the hippocampi progressively deactivated as the task demand increased. This effect was bilateral for controls, whereas the TLE patients showed progressive unilateral deactivation only contralateral to the side of the hippocampal sclerosis and seizure focus. Progressive deactivation of the posterior medial temporal lobe was associated with better performance in all groups. Our results suggest that WM is impaired in unilateral HS and the underlying neural correlates of WM are disrupted. Our findings suggest that hippocampal activity is progressively suppressed as the WM load increases, with maintenance of good performance. Implications for understanding the role of the hippocampus in WM are discussed.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Hipocampo/patología , Hipocampo/fisiopatología , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Esclerosis/fisiopatología , Lóbulo Temporal/fisiopatología , Adulto , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Esclerosis/complicaciones , Estadística como Asunto , Adulto JovenRESUMEN
Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.
Asunto(s)
Atención/fisiología , Epilepsia del Lóbulo Temporal/fisiopatología , Función Ejecutiva/fisiología , Lóbulo Frontal/fisiopatología , Memoria a Corto Plazo/fisiología , Humanos , Pruebas Neuropsicológicas , Lóbulo Temporal/fisiopatologíaRESUMEN
Adrenergic ß2 receptor (ADRß2) agonists are widely used in asthma. Approximately 10% of patients have severe, poorly controlled disease despite extensive use of ADRß2 agonists. Variations in responses to ADRß2 agonists can, in part, be attributed to genetic variation, with 49 different polymorphisms having been identified for the ADRß2 gene. Although clear associations exist between ADRß2 gene polymorphisms, such as +46G>A, and patient response, the importance of these polymorphisms remains controversial. Patient selection, the number of polymorphisms analysed, differences in the type/dose of ADRß2 agonist, use of inhaled corticosteroids and population sizes have all varied. Most studies were limited to mild or moderate asthmatics using ADRß2 agonists sparingly. It is difficult to extrapolate from these studies to individual patients who have severe asthma, use a variety of ADRß2 agonists and do so frequently. The extent to which ADRß2 gene polymorphisms are relevant to asthma management needs further review, both clinically and at the molecular level. In vitro studies have helped to define the functional changes induced by specific ADRß2 gene polymorphisms, including 3'-untranslated region poly-C repeat. The resulting ADRß2 gene haplotypes (rather than genotypes), the interactions among ADRß2 gene haplotypes and variations in the chemistry of different agonists deserve more detailed assessment. Responses to ADRß2 agonists depend on effective downstream signalling following ADRß2 activation and also on receptor regulation. Studies on other regulators of ADRß2 receptor signalling and trafficking may be equally important in understanding the functional role of ADRß2 gene polymorphisms. The role of ADRß2 gene polymorphisms in the pathogenesis and management of severe asthma cannot be clearly defined until more specific and targeted research studies are performed.
Asunto(s)
Agonistas Adrenérgicos beta/uso terapéutico , Asma/tratamiento farmacológico , Resistencia a Medicamentos/genética , Farmacogenética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Preparaciones de Acción Retardada , HumanosRESUMEN
Haemorrhage is one of the leading global causes of maternal mortality. The Rüsch balloon has been used in the treatment of postpartum haemorrhage (PPH) after failure of medical management. It is often effective in tamponading uterine bleeding, thus providing an alternative to hysterectomy. We describe a series of 22 cases in which we used the Rüsch balloon to control massive obstetric haemorrhage after failure to control haemorrhage by medical means. In our study, 13 out of 22 patients (59.1%) required no further interventions after balloon tamponade. Seven patients (31.8%) required hysterectomy to control the bleeding. We include a review of the current literature on balloon tamponade for PPH, including analysis of six relevant case series. This demonstrates a variety of methods based on tamponade to terminate uterine haemorrhage. Our study highlights the benefit of balloon tamponade for massive PPH and the importance of its involvement in labour ward protocols.
Asunto(s)
Oclusión con Balón , Hemorragia Posparto/mortalidad , Hemorragia Posparto/terapia , Adulto , Femenino , Humanos , Embarazo , Resultado del TratamientoRESUMEN
In contrast to the well studied long-term memory dysfunction of temporal lobe epilepsy (TLE) syndromes, data on memory performance of frontal lobe epilepsy (FLE) patients are limited and controversial. Behavioural and functional neuroimaging findings suggest that different regions within the frontal lobes contribute to long-term memory functioning, offering an explanation for the variability on memory function observed on patients with frontal lobe damage. Available evidence suggests memory dysfunction is a common finding on neuropsychological evaluation of FLE patients but prevalence and underlying mechanisms remain poorly understood. Variability on memory performance reported in FLE studies suggest this deficit may be dependant on the areas involved in seizure generation and spread. Recent research findings and the application of cognitive fMRI paradigms to FLE patients holds the promise of increasing understanding further.
Asunto(s)
Epilepsia del Lóbulo Frontal/complicaciones , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Memoria , Animales , Epilepsia del Lóbulo Frontal/psicología , Humanos , Imagen por Resonancia Magnética/métodos , Memoria/fisiología , Trastornos de la Memoria/psicología , Memoria a Largo Plazo/fisiología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E(2), 8-isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear. OBJECTIVE: To assess sputum PGE(2), cysLT, 8-isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E(4) and 9alpha,11beta-prostaglandin (PG)F(2) concentrations, in patients with differing severities of asthma and eosinophilic or non-eosinophilic airway inflammation. METHODS: Inflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non-eosinophilic airway inflammation. Sputum PGE(2), cysLT and 8-isoprostane, and urinary LTE(4) were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer. RESULTS: Sputum PGE(2) concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P<0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P<0.05). Sputum PGE(2) concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non-eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE(4) concentrations were higher in those with eosinophilic airway inflammation (P<0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r(s)=-0.5, P=0.002). There were no significant differences in sputum 8-isoprostane or nitrate concentrations. CONCLUSIONS: Increased airway concentrations of PGE(2) are consistent with the hypothesis that PGE(2) has a bronchoprotective and anti-inflammatory role in patients with more severe asthma. A reduced PGE(2) to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation.
Asunto(s)
Asma/diagnóstico , Cisteína/análisis , Dinoprostona/análisis , Inflamación/diagnóstico , Leucotrienos/análisis , Esputo/inmunología , Adulto , Anciano , Asma/inmunología , Biomarcadores/análisis , Progresión de la Enfermedad , Eosinófilos/inmunología , Femenino , Humanos , Técnicas para Inmunoenzimas , Inflamación/inmunología , Recuento de Leucocitos , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Nitratos/análisisRESUMEN
Haemorrhage, a leading cause of maternal morbidity and mortality, is frequently associated with caesarean section. Allogeneic blood is an increasingly rare and scare resource. Intraoperative Cell Salvage (IOCS) offers the possibility of improving outcome and reducing allogeneic blood transfusion in cases of haemorrhage at caesarean section. The available literature on the use of IOCS in obstetrics demonstrates that there is limited evidence to support or refute the use of IOCS at caesarean section. However, this procedure has been introduced into obstetric practice. Before opinions about its use become solidified, there is a window of opportunity to launch a large multicentre randomised controlled trial to address the current equipoise.
Asunto(s)
Transfusión de Sangre Autóloga/métodos , Cesárea , Hemorragia Posoperatoria/terapia , Hemorragia Posparto/terapia , Medicina Basada en la Evidencia , Femenino , Humanos , Embarazo , Recolección de Tejidos y Órganos/métodosRESUMEN
BACKGROUND: Cyclooxygenase (COX)-2 is an inducible enzyme responsible for catalysing the formation of prostaglandins (PGs) in settings of inflammation. Single nucleotide polymorphisms (SNPs) of the COX-2 gene may influence gene transcription and PG production in the asthmatic airway. OBJECTIVE: To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA). METHODS: The frequencies of 25 COX-2 SNPs were determined in a random population (n=176). The SNPs with a minor allele frequency of >10% were then studied in asthmatic (n=663), non-asthmatic controls (n=513) and AIA subjects (n=58). Genotype, allele and haplotype associations were assessed. Functional assessment of SNPs was performed by transfection into HeLa cells measured using the luciferase dual-reporter assay system. RESULTS: Eighteen COX-2 SNPs were not detected, five were rare and two promoter SNPs, -1195G>A (rs689465), and -1290A>G (rs689466), were further studied. The A allele of the -1195 SNP was present at a significantly higher frequency among all asthmatic subjects (P=0.012). Over 60% of the asthmatic individuals were -1195A homozygotes compared with 54.6% of the control subjects (odds ratio, 1.35; 95% CI, 1.06-1.72, P=0.03). After classifying for severity, the mild asthmatics represented 64.6% of -1195AA individuals, the highest of all the asthma groups compared with 54.6% of the control subjects (odds ratio, 1.5; 95% CI, 1.12-2.02, P=0.02). The -1290A/-1195G/-765G haplotype was associated with a reduced incidence of asthma (odds ratio, 0.76; 95% CI, 0.61-0.95, P=0.017). CONCLUSION: The -1195G>A polymorphism appears to be associated with asthma, and in particular with mild asthma.
Asunto(s)
Asma/genética , Ciclooxigenasa 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Asma/inducido químicamente , Asma/enzimología , Asma/etnología , Australia , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Haplotipos , Células HeLa , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Plásmidos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Transfección , Población BlancaRESUMEN
INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.
Asunto(s)
Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/patología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Giro Parahipocampal/patología , Giro Parahipocampal/fisiología , Adulto , Interpretación Estadística de Datos , Imagen de Difusión por Resonancia Magnética , Electroencefalografía , Femenino , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Convulsiones/patologíaRESUMEN
OBJECTIVES: To assess if mode of delivery is associated with increased symptoms of anal incontinence following childbirth. DESIGN: Systematic review of all relevant studies in English. DATA SOURCES: Medline, Embase, Cochrane Library, bibliographies of retrieved primary articles and consultation with experts. STUDY SELECTION AND DATA EXTRACTION: Data were extracted on study characteristics, quality and results. Exposure to risk factors was compared between women with and without anal incontinence. Categorical data in 2 x 2 contingency tables were used to generate odds ratios. RESULTS: Eighteen studies met the inclusion criteria with 12,237 participants. Women having any type of vaginal delivery compared with a caesarean section have an increased risk of developing symptoms of solid, liquid or flatus anal incontinence. The risk varies with the mode of delivery ranging from a doubled risk with a forceps delivery (OR 2.01, 95% CI 1.47-2.74, P < 0.0001) to a third increased risk for a spontaneous vaginal delivery (OR 1.32, 95% CI 1.04-1.68, P = 0.02). Instrumental deliveries also resulted in more symptoms of anal incontinence when compared with spontaneous vaginal delivery (OR 1.47, 95% CI 1.22-1.78). This was statistically significant for forceps deliveries alone (OR 1.5, 95% CI 1.19-1.89, P = 0.0006) but not for ventouse deliveries (OR 1.31, 95% CI 0.97-1.77, P = 0.08). When symptoms of solid and liquid anal incontinence alone were assessed, these trends persisted but were no longer statistically significant. CONCLUSION: Symptoms of anal incontinence in the first year postpartum are associated with mode of delivery.
Asunto(s)
Parto Obstétrico/efectos adversos , Incontinencia Fecal/etiología , Complicaciones del Trabajo de Parto/etiología , Femenino , Humanos , Embarazo , Factores de RiesgoRESUMEN
Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR.