Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 178
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Platelets ; 33(1): 89-97, 2022 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-33347340

RESUMEN

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.


Asunto(s)
Plaquetas/metabolismo , Ataque Isquémico Transitorio/sangre , Estudios de Casos y Controles , Humanos , Estudios Prospectivos
2.
J Public Health (Oxf) ; 42(1): e18-e25, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30608605

RESUMEN

BACKGROUND: This longitudinal study examined the profile and pregnancy-related behaviours of women who reported smoking in two successive pregnancies when they presented for prenatal care in a large maternity hospital. METHODS: Using the hospital electronic medical records, women who delivered two successive singleton pregnancies during the years 2011-15 were analyzed. Standardized data were computerized by a midwife at the first prenatal visit, following delivery and before discharge. RESULTS: Over the 5 years, 6647 women delivered twice. Overall 5754 (86.6%) were persistent non-smokers in both pregnancies, 609 (9.2%) were persistent smokers in both pregnancies and between pregnancies 202 (3.0%) quit and 82 (1.2%) started smoking. Compared with persistent non-smokers, persistent smokers had higher rates of reported illicit drug use, alcohol consumption and psychological problems and lower rates of planned pregnancy, folic acid supplementation and breastfeeding in both pregnancies (all P < 0.001). In persistent smokers, folic acid supplementation practices deteriorated and illicit drug use increased in the subsequent pregnancy. CONCLUSIONS: We found that approximately one in 10 women smoked in two consecutive pregnancies. Furthermore, compared with non-smokers, persistent smokers were more likely to report other health behaviours associated with adverse pregnancy outcomes and may require additional multidisciplinary support.


Asunto(s)
Cese del Hábito de Fumar , Fumar , Femenino , Humanos , Estudios Longitudinales , Embarazo , Resultado del Embarazo , Atención Prenatal , Fumar/epidemiología
3.
J Hum Nutr Diet ; 33(4): 465-476, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31997529

RESUMEN

BACKGROUND: Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS: In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS: Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day-1 , 1.32 (0.40) g kg-1  day-1 ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg-1  day-1 , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS: Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.


Asunto(s)
Distribución por Edad , Dieta/estadística & datos numéricos , Proteínas en la Dieta/análisis , Distribución por Sexo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Dietéticas Animales/análisis , Registros de Dieta , Ingestión de Energía , Conducta Alimentaria , Femenino , Humanos , Irlanda , Masculino , Comidas , Persona de Mediana Edad , Encuestas Nutricionales , Proteínas de Vegetales Comestibles/análisis , Adulto Joven
4.
BMC Med Inform Decis Mak ; 20(1): 34, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-32075633

RESUMEN

BACKGROUND: Despite the established evidence and theoretical advances explaining human judgments under uncertainty, developments of mobile health (mHealth) Clinical Decision Support Systems (CDSS) have not explicitly applied the psychology of decision making to the study of user needs. We report on a user needs approach to develop a prototype of a mHealth CDSS for Parkinson's disease (PD), which is theoretically grounded in the psychological literature about expert decision making and judgement under uncertainty. METHODS: A suite of user needs studies was conducted in 4 European countries (Greece, Italy, Slovenia, the UK) prior to the development of PD_Manager, a mHealth-based CDSS designed for Parkinson's disease, using wireless technology. Study 1 undertook Hierarchical Task Analysis (HTA) including elicitation of user needs, cognitive demands and perceived risks/benefits (ethical considerations) associated with the proposed CDSS, through structured interviews of prescribing clinicians (N = 47). Study 2 carried out computational modelling of prescribing clinicians' (N = 12) decision strategies based on social judgment theory. Study 3 was a vignette study of prescribing clinicians' (N = 18) willingness to change treatment based on either self-reported symptoms data, devices-generated symptoms data or combinations of both. RESULTS: Study 1 indicated that system development should move away from the traditional silos of 'motor' and 'non-motor' symptom evaluations and suggest that presenting data on symptoms according to goal-based domains would be the most beneficial approach, the most important being patients' overall Quality of Life (QoL). The computational modelling in Study 2 extrapolated different factor combinations when making judgements about different questions. Study 3 indicated that the clinicians were equally likely to change the care plan based on information about the change in the patient's condition from the patient's self-report and the wearable devices. CONCLUSIONS: Based on our approach, we could formulate the following principles of mHealth design: 1) enabling shared decision making between the clinician, patient and the carer; 2) flexibility that accounts for diagnostic and treatment variation among clinicians; 3) monitoring of information integration from multiple sources. Our approach highlighted the central importance of the patient-clinician relationship in clinical decision making and the relevance of theoretical as opposed to algorithm (technology)-based modelling of human judgment.


Asunto(s)
Toma de Decisiones Clínicas , Sistemas de Apoyo a Decisiones Clínicas , Personal de Salud/psicología , Enfermedad de Parkinson/prevención & control , Telemedicina , Grecia , Humanos , Italia , Juicio , Modelos Teóricos , Teoría Psicológica , Eslovenia , Reino Unido
5.
Ir Med J ; 110(6): 580, 2017 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-28952670

RESUMEN

There is international consensus that smoking cessation in the first half of pregnancy improves foetal outcomes. We surveyed all 19 maternity units nationally about their antenatal smoking cessation practices. All units recorded details on maternal smoking at the first antenatal visit. Only one unit validated the self-reported smoking status of pregnant women using a carbon monoxide breath test. Twelve units (63%) recorded timing of smoking cessation. In all units women who reported smoking were given verbal cessation advice. This was supported by written advice in 12 units (63%), but only six units (32%) had all midwives trained to provide this advice. Only five units (26%) reported routinely revisiting smoking status later in pregnancy. Although smoking is an important modifiable risk factor for adverse pregnancy outcomes, smoking cessation services are inadequate in the Irish maternity services and there are variations in practices between hospitals.


Asunto(s)
Mujeres Embarazadas , Cese del Hábito de Fumar/estadística & datos numéricos , Prevención del Hábito de Fumar/estadística & datos numéricos , Fumar , Femenino , Humanos , Irlanda , Embarazo , Atención Prenatal/normas , Atención Prenatal/estadística & datos numéricos
6.
Osteoarthritis Cartilage ; 24(7): 1274-83, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26903200

RESUMEN

OBJECTIVE: Abnormal metabolic activities of chondrocytes may cause articular cartilage (AC) degradation, but key transcription factors regulating metabolic activities in AC of aging individuals remain unknown. This study aimed to investigate the role of transcription factor NFAT1 in regulating the expression of anabolic and catabolic molecules in AC of aged mice. METHODS: The hip, knee, and shoulder joints of BALB/c mice were harvested at 6, 12, 15, 18, and 24 months of age for histopathological and immunohistochemical (IHC) analyses. Total RNA was isolated from AC for gene expression. Genomic DNA and chromatin were prepared from AC for methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP) assays. RESULTS: NFAT1 expression in AC of mice was significantly decreased after 12 months of age, which was associated with reduced proteoglycan staining, decreased expression of chondrocyte markers, and increased expression of interleukin-1ß. Forced Nfat1 expression in chondrocytes from aged mice significantly reversed the abnormal metabolic activities. ChIP assays confirmed that NFAT1 bound to the promoter of the Acan, Col2a1, Col9a1, Col11a1, Il1b, Mmp13 and Tnfa genes in articular chondrocytes of aged mice. ChIP and MeDIP assays revealed that reduced NFAT1 expression in AC of aged mice was regulated by epigenetic histone methylation at the promoter region and was correlated with increased DNA methylation at introns 1 and 10 of the Nfat1 gene. CONCLUSION: NFAT1 is a transcriptional regulator of multiple anabolic and catabolic genes in AC of aged mice. Epigenetically mediated reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice.


Asunto(s)
Condrocitos , Animales , Cartílago Articular , Células Cultivadas , Metilación de ADN , Interleucina-1beta , Ratones , Factores de Transcripción NFATC , Proteoglicanos
7.
Scand J Med Sci Sports ; 26(6): 630-7, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26060092

RESUMEN

The relative contribution of carbohydrate and fat oxidation to energy expenditure during exercise is dependent on variables including exercise intensity, mode, and recruited muscle mass. This study investigated patterns of substrate utilization during two non-weightbearing exercise modalities, namely cycling and rowing. Thirteen young, moderately trained males performed a continuous incremental (3-min stages) exercise test to exhaustion on separate occasions on an electronically braked cycle (CYC) ergometer and an air-braked rowing (ROW) ergometer, respectively. On two further occasions, participants performed a 20-min steady-state exercise bout at ∼50%VO2peak on the respective modalities. Despite similar oxygen consumption, rates of fat oxidation (FATox ) were ∼45% higher during ROW compared with CYC (P < 0.05) across a range of power output increments. The crossover point for substrate utilization occurred at a higher relative exercise intensity for ROW than CYC (57.8 ± 2.1 vs 42.1 ± 3.6%VO2peak , P < 0.05). During steady-state submaximal exercise, the higher FATox during ROW compared with CYC was maintained (P < 0.05), but absolute FATox were 42% (CYC) and 28% (ROW) lower than during incremental exercise. FATox is higher during ROW compared with CYC exercise across a range of exercise intensities matched for energy expenditure, and is likely as a consequence of larger muscle mass recruited during ROW.


Asunto(s)
Prueba de Esfuerzo/instrumentación , Ejercicio Físico/fisiología , Metabolismo de los Lípidos/fisiología , Esfuerzo Físico/fisiología , Pruebas Respiratorias , Metabolismo de los Hidratos de Carbono/fisiología , Frecuencia Cardíaca , Humanos , Masculino , Oxidación-Reducción , Consumo de Oxígeno , Resistencia Física/fisiología , Adulto Joven
8.
J Neurol Neurosurg Psychiatry ; 86(4): 460-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25033981

RESUMEN

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.


Asunto(s)
Estenosis Carotídea/metabolismo , Embolia Intracraneal/metabolismo , Trombina/biosíntesis , Anciano , Estenosis Carotídea/tratamiento farmacológico , Femenino , Humanos , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Ultrasonografía Doppler Transcraneal
9.
Eur J Neurol ; 21(7): 969-e55, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24712648

RESUMEN

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.


Asunto(s)
Estenosis Carotídea/sangre , Endotelio/metabolismo , Embolia Intracraneal/sangre , Factor de von Willebrand , Anciano , Biomarcadores/sangre , Isquemia Encefálica/etiología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Humanos , Embolia Intracraneal/diagnóstico por imagen , Ataque Isquémico Transitorio/etiología , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/etiología , Ultrasonografía
10.
J Neurol Sci ; 463: 123118, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39024743

RESUMEN

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.


Asunto(s)
Proteína ADAMTS13 , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Factor de von Willebrand , Humanos , Factor de von Willebrand/metabolismo , Proteína ADAMTS13/sangre , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Persona de Mediana Edad , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Proyectos Piloto , Clopidogrel/uso terapéutico , Precursores de Proteínas
11.
Eur J Neurol ; 20(2): 344-52, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22994699

RESUMEN

BACKGROUND AND PURPOSE: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. METHODS: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. RESULTS: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. CONCLUSIONS: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.


Asunto(s)
Plaquetas/efectos de los fármacos , Ataque Isquémico Transitorio/fisiopatología , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Accidente Cerebrovascular/fisiopatología , Anciano , Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas/fisiología , Clopidogrel , Estudios Cruzados , Femenino , Humanos , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/inmunología , Leucocitos/fisiología , Masculino , Persona de Mediana Edad , Selectina-P/metabolismo , Proyectos Piloto , Activación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/tratamiento farmacológico , Tetraspanina 30/metabolismo , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Ticlopidina/uso terapéutico
12.
Allergy ; 67(1): 33-40, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21919915

RESUMEN

BACKGROUND: The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy. METHODS: IRF4 and its target genes were examined in allergen-challenged CD4(+) cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP-chips), computational target prediction, and RNAi knockdowns. RESULTS: IRF4 increased in allergen-challenged CD4(+) cells from patients with IAR, and functional studies supported its role in Th2 cell activation. IRF4 ChIP-chip showed that IRF4 regulated a large number of genes relevant to Th cell differentiation. However, neither Th1 nor Th2 cytokines were the direct targets of IRF4. To examine whether IRF4 induced Th2 cytokines via one or more downstream TFs, we combined gene expression microarrays, ChIP-chips, and computational target prediction and found a putative intermediary TF, namely ETS1 in allergen-challenged CD4(+) cells from allergic patients. ETS1 increased significantly in allergen-challenged CD4(+) cells from patients compared to controls. Gene expression microarrays before and after ETS1 RNAi knockdown showed that ETS1 induced Th2 cytokines as well as disease-related pathways. CONCLUSIONS: Increased expression of IRF4 in allergen-challenged CD4(+) cells from patients with intermittent allergic rhinitis leads to activation of a complex transcriptional program, including Th2 cytokines.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Regulación de la Expresión Génica/inmunología , Factores Reguladores del Interferón/biosíntesis , Proteína Proto-Oncogénica c-ets-1/biosíntesis , Rinitis Alérgica Estacional/metabolismo , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/inmunología , Separación Celular , Inmunoprecipitación de Cromatina , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Factores Reguladores del Interferón/genética , Activación de Linfocitos/inmunología , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteína Proto-Oncogénica c-ets-1/genética , ARN Interferente Pequeño , Rinitis Alérgica Estacional/genética , Rinitis Alérgica Estacional/inmunología , Células Th2/citología , Células Th2/inmunología
13.
J Neurol Sci ; 441: 120334, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36030623

RESUMEN

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.


Asunto(s)
Isquemia Encefálica , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adenosina Difosfato/metabolismo , Adenosina Difosfato/farmacología , Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas , Isquemia Encefálica/metabolismo , Dipiridamol/metabolismo , Dipiridamol/farmacología , Dipiridamol/uso terapéutico , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Activación Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos
14.
Ir J Med Sci ; 189(3): 1023-1026, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31898163

RESUMEN

BACKGROUND: Axillary hyperhidrosis is a common complaint affecting 5% of the general population. It can significantly impact quality of life (QOL) and may be extremely debilitating. Administration of intra-dermal botulinum toxin type-A (Botox) has been proven to be effective in managing axillary hyperhidrosis; however, to date, no long-term data has assessed its efficacy. AIM: We aim to assess long-term (> 5 years) QOL outcomes in this patient cohort. METHODS: In this single-centre series, all patients attending for axillary botox, with five or more years of follow-up, were prospectively included. QOL was assessed in all patients using the validated assessment tool, the modified Dermatology Life Quality Index (DLQI). Standard statistical methods were utilised with data reported as mean (± standard deviation). Subgroup analysis utilising previously published departmental data allowed for further assessment of change in QOL over time. RESULTS: A total of 75 patients (83% female) met the inclusion criteria with 67% completing the DLQI assessment. Follow-up ranged from 5 to 10 years with a mean age of 37.6 years (± 8.82). The mean number of treatments over the study period was 12 (± 3.1). Mean overall post-treatment DLQI score was 1.6 (± 2.01). This represented a significant improvement in patient QOL (p = < 0.0001) associated with long-term botox application. This statistical significance was identified consistently across all components of the DLQI tool. CONCLUSION: These data suggest that the established early QOL benefits associated with intra-dermal botox administration for AH are sustained in the long term. This benefit was seen across all subsets of the DLQI tool.


Asunto(s)
Axila/anomalías , Toxinas Botulínicas Tipo A/uso terapéutico , Hiperhidrosis/tratamiento farmacológico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intradérmicas , Masculino , Factores de Tiempo , Resultado del Tratamiento
15.
J Neurol ; 267(1): 168-184, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31606758

RESUMEN

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.


Asunto(s)
Aspirina/farmacología , Plaquetas , Estenosis Carotídea/tratamiento farmacológico , Embolia Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Isquemia Encefálica/tratamiento farmacológico , Estenosis Carotídea/diagnóstico por imagen , Femenino , Humanos , Embolia Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Ultrasonografía Doppler Transcraneal
16.
J Prev Alzheimers Dis ; 5(3): 175-183, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29972210

RESUMEN

OBJECTIVES: To investigate the impact of a six-month multi-ingredient nutrition supplement intervention (Smartfish®), containing omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and whey protein, on cognitive function in Irish older adults. DESIGN: Double-blind, randomised controlled trial (ClinicalTrials.gov: NCT02001831). A quantitative, mixed-model design was employed in which the dependent variable (cognitive function) was analysed with a between-subjects factor of group (placebo, intervention) and within-subjects factor of testing occasion (baseline, three-months, six-months). SETTING: Community-based intervention including assessments conducted at University College Dublin, Ireland. PARTICIPANTS: Thirty-seven community-dwelling older adults (68-83 years; mean (x̄)= 75.14 years; standard deviation (SD)= 3.64; 18 males) with normal cognitive function (>24 on the Mini Mental State Examination) were assigned to the placebo (n= 17) or intervention (n= 20) via a block randomisation procedure. INTERVENTION: Daily consumption for six-months of a 200mL liquid juice intervention comprising 3000mg omega-3 PUFAs [1500mg docosahexaenoic acid (DHA) and 1500mg eicosapentaenoic acid (EPA)], 10µg vitamin D3, 150mg resveratrol and 8g whey protein isolate. The placebo contained 200mL juice only. MEASUREMENTS: A standardised cognitive assessment battery was conducted at baseline and follow-ups. Individual test scores were z-transformed to generate composite scores grouped into cognitive domains: executive function, memory, attention and sensorimotor speed. Motor imagery accuracy and subjective awareness of cognitive failures variables were computed from raw scores. RESULTS: A hierarchical statistical approach was used to analyse the data; first, by examining overall cognitive function, then by domain, and then by individual test scores. Using mixed between-within subjects, analyses of variance (ANOVAs), no significant differences in overall cognitive function or composite cognitive domains were observed between groups over time. The only significant interaction was for Stroop Color-Word Time (p< 0.05). The intervention group demonstrated reduced task completion time at three- and six-month follow-ups, indicating enhanced performance. CONCLUSION: The present nutrition intervention encompassed a multi-ingredient approach targeted towards improving cognitive function, but overall had only a limited beneficial impact in the older adult sample investigated. Future investigations should seek to establish any potential clinical applications of such targeted interventions with longer durations of supplementation, or in populations with defined cognitive deficits.


Asunto(s)
Cognición/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Resveratrol/farmacología , Vitamina D/farmacología , Proteína de Suero de Leche/farmacología , Anciano , Anciano de 80 o más Años , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas
17.
J Clin Invest ; 80(3): 812-7, 1987 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-3040806

RESUMEN

Multiple components of vascular alpha adrenergic responsiveness were investigated in twenty-four men with mild hypertension and eighteen age- and weight-matched normotensive controls. Arterial plasma norepinephrine (paNE), an index of sympathetic drive, was increased in hypertensives compared to normotensives (mean +/- SE), 199 +/- 24 vs. 134 +/- 11 pg/ml, P less than 0.02. The effective concentration of intra-arterial (iaNE) increasing forearm vascular resistance (FAVR) 30% (NE-EC30, an index of vascular alpha-receptor sensitivity) was similar in normotensives and hypertensives, 9 +/- 1 vs. 13 +/- 3 ng/100 ml per min, respectively, P greater than 0.3. The phentolamine induced reduction in FAVR, an index of vascular alpha-tone, was greater in hypertensives, -21.3 +/- 1.8 vs. normotensives, -14.9 +/- 1.2 U, P less than 0.02. We interpret these data as evidence for normal vascular alpha-receptor sensitivity to norepinephrine in mild hypertensives. Consequently, the increased sympathetic drive in mild hypertensives explains the elevated vascular alpha-tone. Although vascular alpha-receptor sensitivity to iaNE was normal, the FAVR responses at high doses (reactivity) were greater in hypertensives to regional infusion of both NE and angiotensin II. This "nonspecific" enhancement of vascular reactivity is probably explained by structural vascular changes in hypertensives.


Asunto(s)
Hipertensión/fisiopatología , Receptores Adrenérgicos alfa/fisiología , Vasoconstricción , Adulto , Arterias , Fenómenos Biomecánicos , Relación Dosis-Respuesta a Droga , Antebrazo/irrigación sanguínea , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Norepinefrina , Resistencia Vascular/efectos de los fármacos
19.
Curr Genomics ; 8(6): 379-97, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19412438

RESUMEN

Gastric adenocarcinoma occurs via a sequence of molecular events known as the Correa's Cascade which often progresses over many years. Gastritis, typically caused by infection with the bacterium H. pylori, is the first step of the cascade that results in gastric cancer; however, not all cases of gastritis progress along this carcinogenic route. Despite recent antibiotic intervention of H. pylori infections, gastric adenocarcinoma remains the second most common cause of cancer deaths worldwide. Intestinal metaplasia is the next step along the carcinogenic sequence after gastritis and is considered to be a precursor lesion for gastric cancer; however, not all patients with intestinal metaplasia develop adenocarcinoma and little is known about the molecular and genetic events that trigger the progression of intestinal metaplasia into adenocarcinoma. This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia. The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis. There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy.

20.
Ir J Med Sci ; 176(1): 33-6, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17849521

RESUMEN

BACKGROUND: Intraoperative cell salvage (ICS) is the recovery, anticoagulation, filtration and reinfusion of blood lost during surgery. The aim of this study is to determine the safety and efficacy of ICS in emergency and elective abdominal aortic surgery. METHODS: This study reviews volumes of blood loss, blood salvaged with ICS, allogenic blood requirements, and clinical outcomes in patients undergoing abdominal aortic surgery using ICS. RESULTS: Seventy-nine patients undergoing abdominal aortic surgery are included. Supplemental allogenic blood was not required in 45/79 (57%) of all patients. Transfusion with allogenic blood was not necessary in 41/63 (66%) of elective abdominal aortic aneurysm repairs. ICS was associated with no major complications. CONCLUSION: ICS is a safe procedure and substantially reduces the need for blood transfusion in patients undergoing abdominal aortic surgery. It may substantially alleviate shortages of allogenic blood and should be part of the armamentarium of vascular units.


Asunto(s)
Aorta Abdominal/cirugía , Enfermedades de la Aorta/cirugía , Pérdida de Sangre Quirúrgica/prevención & control , Conservación de la Sangre/métodos , Transfusión de Sangre Autóloga/métodos , Volumen Sanguíneo , Cuidados Intraoperatorios/métodos , Resultado del Tratamiento , Bases de Datos como Asunto , Femenino , Humanos , Masculino , Estudios Prospectivos , Terapia Recuperativa
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA