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2.
Clin Microbiol Infect ; 25(4): 454-461, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29964235

RESUMEN

OBJECTIVES: To evaluate the relationship between individual bacterial and viral pathogens and disease severity. METHODS: Children <18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up). RESULTS: Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease. CONCLUSIONS: In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.


Asunto(s)
Adenoviridae/aislamiento & purificación , Gastroenteritis , Norovirus/aislamiento & purificación , Rotavirus/aislamiento & purificación , Salmonella/aislamiento & purificación , Adolescente , Adulto , Canadá , Niño , Gastroenteritis/diagnóstico , Gastroenteritis/tratamiento farmacológico , Gastroenteritis/microbiología , Humanos , Lactante , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
3.
Thromb Haemost ; 112(2): 276-86, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24953051

RESUMEN

It was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 - 21.9)/1,000 person-years vs 8.4 (7.7 - 9.1) in controls (p<0.001), mortality 40.1 (36.8 - 43.6)/1,000 person-years vs 20.9 (19.8 - 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 - 10.8)/1,000 person-years vs 6.5 (5.9 - 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 - 0.71) for stroke, and 0.56 (0.36 - 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 - 1.29) for stroke, and 0.80 (0.55 - 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Hallazgos Incidentales , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/prevención & control , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Enfermedades Asintomáticas , Fibrilación Atrial/mortalidad , Estudios de Casos y Controles , Causas de Muerte , Bases de Datos Factuales , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto Joven
4.
Clin Toxicol (Phila) ; 51(8): 761-6, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23957582

RESUMEN

CONTEXT: Seizures may be the presenting manifestation of acute poisoning in children. Knowledge of the etiologic agent, or likely drug-class exposure, is crucial to minimize morbidity and optimize care. OBJECTIVES: To describe the agents most commonly responsible for pediatric drug-induced seizures, whose evaluation included a medical toxicology consultation in the United States. METHODS: Using the 37 participating sites of the Toxicology Investigators Consortium (ToxIC) Case Registry, a cross-country surveillance tool, we conducted an observational study of a prospectively collected cohort. We identified all pediatric (younger than 18 years) reports originating from an Emergency Department (ED) which included a chemical or drug-induced seizure, and required a medical toxicology consultation between April 1, 2010 and March 31, 2012. Results. We identified 142 pediatric drug-induced seizure cases (56% male), which represent nearly 5% of pediatric cases requiring bedside consultation by medical toxicologists. One-hundred and seven cases (75%) occurred in children aged 13-18 years, and 86 (61%) resulted from intentional ingestions. Antidepressants were the most commonly identified agents ingested (n = 61; 42%), of which bupropion was the leading drug (n = 30; 50% of antidepressants), followed by anticholinergics/antihistamines (n = 31; 22%). All antidepressant-induced seizures in teenagers were intentional and represented self-harm behavior. Sympathomimetic agents, including street drugs, represent the most common agents in children younger than 2 years (n = 4/19). CONCLUSION: Antidepressants, and specifically bupropion, are presently the most common medications responsible for pediatric drug-induced seizures requiring medical toxicology consultation in the United States. In teenagers presenting with new-onset seizures of unknown etiology, the possibility of deliberate self-poisoning should be explored, since most drug-induced seizures in this age group resulted from intentional ingestion.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Intoxicación/epidemiología , Convulsiones/inducido químicamente , Conducta Autodestructiva/epidemiología , Adolescente , Distribución por Edad , Antidepresivos/envenenamiento , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Vigilancia de la Población , Estudios Prospectivos , Derivación y Consulta/estadística & datos numéricos , Sistema de Registros , Estados Unidos/epidemiología
5.
Eur J Cardiovasc Prev Rehabil ; 18(2): 278-86, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20606594

RESUMEN

OBJECTIVE: To determine if the improved risk factor profile at 1 year attributed to the Choice of Health Options In prevention of Cardiovascular Events (CHOICE) program was maintained at 4 years. DESIGN: Single-blind randomized controlled trial with post-hoc 476 months follow-up (76% complete). SETTING: Australian tertiary referral hospital. PATIENTS: Two hundred and eight acute coronary syndrome survivors. INTERVENTIONS: Acute coronary syndrome survivors not accessing cardiac rehabilitation (CR) were randomized to control (n=72) or CHOICE (n=72) comprising the tailored risk factor reduction packaged as a clinic visit and 3 months phone support. A contemporary CR reference group were also recruited (n=64). Blinded risk assessment occurred at baseline, 1 and 4 years. MAIN OUTCOME MEASURES: Total cholesterol, systolic blood pressure, smoking status, physical activity. RESULTS: One year improvements in all the modifiable risk factors achieved in CHOICE were maintained at 4 years. CHOICE and control were well-matched at baseline. At 4 years, there was a trend towards lower total cholesterol in CHOICE compared with controls (mean 4.0±0.1 vs. 4.2±0.1 mmol/l, P=0.05), significantly better systolic blood pressure (mean 132.2±2.1 vs. 136.8±2.0 mmHg, P=0.01), physical activity scores (1200±209 vs. 968±196 metabolic equivalent min/week, P=0.02) and proportion with three or more risk factors above national targets (20 vs. 42%,P=0.02). Participants in CHOICE were at higher baseline risk than CR but at 4 years they had similar risk factor profiles. CONCLUSION: Participants in CHOICE maintained favorable changes in coronary risk profile at 4 years compared with control, indicating that CHOICE is an effective long-term intervention among those not accessing facility-based CR.


Asunto(s)
Síndrome Coronario Agudo/terapia , Manejo de Caso , Prevención Secundaria/métodos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/prevención & control , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Colesterol/sangre , Ejercicio Físico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Nueva Gales del Sur , Medición de Riesgo , Factores de Riesgo , Método Simple Ciego , Cese del Hábito de Fumar , Factores de Tiempo , Resultado del Tratamiento
6.
Int J Cardiol ; 146(3): 408-14, 2011 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-21112101

RESUMEN

AIMS: Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). CONCLUSIONS: Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.


Asunto(s)
Benzazepinas/farmacología , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Anciano , Método Doble Ciego , Femenino , Humanos , Ivabradina , Masculino , Ultrasonografía
7.
Int J Cardiol ; 145(3): 481-6, 2010 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-20444512

RESUMEN

BACKGROUND: We aimed to determine whether the frequency of General Practitioner and Cardiologist consultations impacted on improvements in risk factors in Choice of Health Options in Reducing Cardiovascular Events (CHOICE) randomised controlled trial. METHODS: Retrospective subgroup analysis of single-blind randomised controlled trial. We included acute coronary syndrome survivors not accessing cardiac rehabilitation in the CHOICE trial whose General Practitioner or Cardiologist returned a visit frequency survey. The CHOICE group participated in tailored risk factor reduction packaged as clinic visit plus 3 months telephone support. Controls participated in physician-directed usual medical care. We compared total cholesterol, systolic blood pressure, smoking status, physical activity, number of modifiable risk factors and medications with frequency of medical consultations at baseline and 12 months. RESULTS: Most control and CHOICE patients saw their General Practitioner≥5 times (85% vs 90%) and Cardiologist at least once (65% vs 57%). CHOICE patients had a significantly better modifiable risk profile (factor levels and multiples) and more patients were on evidence-based medications at 12 months compared to controls. In CHOICE, the significant reduction in total cholesterol was unrelated to medical visits but lower systolic blood pressure was significant in patients who saw their General Practitioner≥5 compared with ≤4 times. In controls, frequency of medical visits was not associated with any changes in risk profile. CONCLUSIONS: Acute coronary syndrome survivors receiving frequent medical follow-up without packaged secondary prevention had no improvement in multiple risk factors over 12 months. CHOICE patients who saw their doctors frequently were more likely to have significantly reduced systolic blood pressure and be on evidence-based medications.


Asunto(s)
Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/terapia , Cardiología/estadística & datos numéricos , Medicina General/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Síndrome Coronario Agudo/rehabilitación , Anciano , Presión Sanguínea , Medicina Basada en la Evidencia/estadística & datos numéricos , Femenino , Encuestas de Atención de la Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo
9.
Heart ; 95(6): 468-75, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18801781

RESUMEN

OBJECTIVE: To determine the effect of a new CHOICE (Choice of Health Options In prevention of Cardiovascular Events) programme on cardiovascular risk factors in acute coronary syndrome (ACS) survivors. DESIGN: Single-blind randomised controlled trial. SETTING: Tertiary referral hospital in Sydney Australia. PATIENTS: 144 ACS survivors who were not accessing standard cardiac rehabilitation. Data were also collected on a further 64 ACS survivors attending standard cardiac rehabilitation. INTERVENTION: The CHOICE group (n = 72) participated in a brief, patient-centred, modular programme comprising a clinic visit plus telephone support, encompassing mandatory cholesterol lowering and tailored preferential risk modification. The control group (n = 72) participated in continuing conventional care but no centrally coordinated secondary prevention. MAIN OUTCOME MEASURES: Values for total cholesterol, systolic blood pressure, smoking status and physical activity. RESULTS: CHOICE and control groups were well matched at baseline. At 12 months, the CHOICE group (n = 67) had significantly better risk factor levels than controls (n = 69) for total cholesterol (TC) (mean (SEM) 4.0 (0.1) vs 4.7 (0.1) mmol/l, p<0.001), systolic blood pressure (131.6 (1.8) vs 143.9 (2.3) mm Hg, p<0.001), body mass index (28.9 (0.7) vs 31.2 (0.7) kg/m(2), p = 0.025) and physical activity (1369.1 (167.2) vs 715.1 (103.5) METS/kg/min, p = 0.001) as well as a better knowledge of risk factor targets. Also at 1 year, fewer CHOICE participants (21%) had three or more risk factors above widely recommended levels then controls (72%) (p<0.001). CONCLUSIONS: Participation in a brief CHOICE programme significantly improved the modifiable risk profiles and risk factor knowledge of ACS survivors over 12 months. CHOICE is an effective alternative for dealing with the widespread underuse of existing secondary prevention programmes. TRIAL REGISTRATION NUMBER: ISRCTN42984084.


Asunto(s)
Síndrome Coronario Agudo/rehabilitación , Participación del Paciente/métodos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/psicología , Anciano , Presión Sanguínea , Fármacos Cardiovasculares/uso terapéutico , Conducta de Elección , Colesterol/sangre , Utilización de Medicamentos/estadística & datos numéricos , Métodos Epidemiológicos , Femenino , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Calidad de Vida , Resultado del Tratamiento
10.
BMC Cardiovasc Disord ; 8: 25, 2008 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-18838009

RESUMEN

BACKGROUND: Although morbidity and mortality from coronary heart disease (CHD) are high, only a minority of acute coronary syndrome (ACS) survivors accesses an effective secondary prevention program. We aim to determine whether the previously proven CHOICE program can be replicated at multiple sites and whether ongoing reinforcement further improves risk factor modification. METHODS/DESIGN: Participants eligible for but not accessing standard cardiac rehabilitation will be randomly allocated to either a previously tested 3-month CHOICE program or a 30-month CHOICE program (CHOICE-plus). Both groups will participate in individualised risk factor modules of differing duration that involve choice, goal setting and telephone follow-up for three months. CHOICE-plus will also receive additional face-to-face and telephone reinforcement between three and 30 months. At one site we will recruit a randomised control group, receiving conventional care. Primary outcomes are lipid levels, blood pressure, physical activity levels and smoking rates. Secondary outcomes include readmission rates, death, the number of risk factors, other modifiable risk factors, quality of life and process evaluation measures over three years. DISCUSSION: We present the rationale and design of a multi-centre, replication study testing a modular approach for the secondary prevention of CHD following an ACS. TRIAL REGISTRATION: [Clinical Trial Registration Number, ACTRN12608000182392].


Asunto(s)
Síndrome Coronario Agudo/prevención & control , Síndrome Coronario Agudo/rehabilitación , Enfermedad Coronaria/prevención & control , Enfermedad Coronaria/rehabilitación , Servicios Preventivos de Salud , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/mortalidad , Enfermedad Coronaria/etiología , Enfermedad Coronaria/mortalidad , Interpretación Estadística de Datos , Humanos , Nueva Gales del Sur/epidemiología , Selección de Paciente , Servicios Preventivos de Salud/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud , Tamaño de la Muestra , Prevención Secundaria , Factores de Tiempo , Resultado del Tratamiento
11.
Thromb Res ; 122(5): 674-82, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18420257

RESUMEN

BACKGROUND: Mice lacking plasminogen (PG-/-) require alternative pathways of fibrinolysis for survival. This may depend on polymorphonuclear leukocytes (PMN) that can clear soluble and insoluble fibrin(ogen) through PG-independent processes. Our objective was to demonstrate that PMNs from PG-/- mice exhibit increased Mac-1 dependent phagocytic activity, which may explain their increased fibrin(ogen)lytic activity compared with wild type (PG+/+) mice. METHODS: Phagocytic activity of PMNs from PG-/- and PG+/+ mice was compared following exposure to Staphylococcus aureus (S. aureus) particles and the expression of Mac-1 was assessed in parallel by flow cytometric analysis. Resistance to phorbol-12-myristate-13-acetate (PMA)-induced cell death was compared between PMNs from the different genotypes. RESULTS: Stimulation of PG-/- PMNs by opsonized S. aureus diluted in PG-/- plasma significantly increased phagocytosis (15-fold) compared with stimulation of PG+/+ PMNs in PG+/+ plasma. Incubation of PG-/- PMNs with PG+/+ plasma (control) or PG-/- plasma supplemented with human PG inhibited this increased phagocytic activity. Mac-1 cell surface density increased 6.2+/-1.0-fold in PG-/- PMNs versus 2.9+/-0.6-fold in PG+/+ PMNs (P < 0.01) indicating that Mac-1 may be associated with increased phagocytic activity. Supporting this, treatment of PG-/- PMNs with an anti-Mac-1 antibody in PG-/- plasma inhibited phagocytic activity. In addition, physiologic PG blocked Mac-1 accessibility at the surface of PMNs. Addition of PMA resulted in 33% death of PMNs from PG-/- mice versus 68% in PG+/+ controls (P < 0.001). CONCLUSIONS: PMNs from PG-/- mice exhibit a Mac-1 dependent increase in phagocytic activity that is suppressed with human PG, an anti-Mac-1 antibody or the plasma from PG+/+ mice. The propensity for PMNs from PG-/- mice to be activated in response to PMA together with their relative resistance to PMA-toxicity may contribute to increased PMN half-life and enhanced fibrin(ogen) clearance in the setting of PG deficiency.


Asunto(s)
Neutrófilos/fisiología , Fagocitosis/fisiología , Plasminógeno/deficiencia , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/fisiología , Secuencia de Bases , Cartilla de ADN/genética , Femenino , Fibrinólisis/fisiología , Antígeno de Macrófago-1/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Fagocitosis/efectos de los fármacos , Fagocitosis/genética , Plasminógeno/genética , Plasminógeno/fisiología , Staphylococcus aureus/inmunología , Acetato de Tetradecanoilforbol/farmacología
12.
BMC Cardiovasc Disord ; 6: 26, 2006 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-16762079

RESUMEN

BACKGROUND: Coronary heart disease (CHD) is a major cause of morbidity and mortality in Australia and it is recommended that all persons with unstable angina (UA) or myocardial infarction (MI) participate in secondary prevention as offered in cardiac rehabilitation (CR) programs. However, the majority of patients do not access standard CR and have higher baseline coronary risk and poorer knowledge of CHD than those persons due to commence CR. The objective of this study is to investigate whether a modular guided self-choice approach to secondary prevention improves coronary risk profile and knowledge in patients who do not access standard CR. METHODS/DESIGN: This randomised controlled trial with one year follow-up will be conducted at a tertiary referral hospital. Participants eligible for but not accessing standard CR will be randomly allocated to either a modular or conventional care group. Modular care will involve participation in individualised modules that involve choice, goal-setting and coaching. Conventional care will involve ongoing heart disease management as directed by the participant's doctors. Both modular and conventional groups will be compared with a contemporary reference group of patients attending CR. Outcomes include measured modifiable risk factors, relative heart disease risk and knowledge of risk factors. DISCUSSION: We present the rationale and design of a randomised controlled trial testing a modular approach for the secondary prevention of coronary heart disease following acute coronary syndrome.


Asunto(s)
Angina de Pecho/complicaciones , Infarto del Miocardio/complicaciones , Educación del Paciente como Asunto/métodos , Angina de Pecho/rehabilitación , Conducta de Elección , Terapia por Ejercicio , Cardiopatías/epidemiología , Cardiopatías/prevención & control , Humanos , Infarto del Miocardio/rehabilitación , Obesidad/epidemiología , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Factores de Riesgo , Síndrome
14.
J Thromb Haemost ; 4(1): 98-106, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16409458

RESUMEN

OBJECTIVES: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. PATIENTS AND METHODS: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. RESULTS: CRP (5-25 microg mL(-1)) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than non-adherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. CONCLUSIONS: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.


Asunto(s)
Proteína C-Reactiva/farmacología , Enfermedad de la Arteria Coronaria/sangre , Trombofilia/inducido químicamente , Adulto , Anciano , Angina de Pecho/sangre , Estudios de Casos y Controles , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón gamma/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Tromboplastina/genética
15.
Mult Scler ; 11(6): 683-90, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16320728

RESUMEN

PURPOSE: To determine the efficacy of a small molecule inhibitor of alpha4 integrin (CT301) at reversing the clinical, pathological and MR-detectable deficits associated with the acute phase of experimental allergic encephalomyelitis (EAE). MATERIALS AND METHODS: EAE was induced in 36 female Hartley guinea pigs, and the treatment period was from day 11 to day 17 post-immunization. Animals received either saline (n = 12), anti-alpha4 integrin antibody (AN100226m; n = 12) or CT301 (n = 12). T2-weighted fast spin echo and T1-weighted pre- and post-contrast scans were performed at the beginning (day 11) and end (day 18) of the treatment period, and scored for cerebral inflammation and gadolinium enhancement. T1-weighted images were further analyzed to quantify this enhancement as a measure of blood-brain barrier integrity. Dissected CNS was evaluated for inflammation and demyelination. RESULTS: CT301 successfully reversed two clinical indicators of disease over the course of the treatment period. These animals showed decreased T2-weighted abnormalities, as well as a reduction in gadolinium leakage on T1-weighted images. Meningeal and perivascular inflammation was decreased by anti-alpha4 integrin treatments. CONCLUSION: CT301 effectively reverses the clinical, pathological and MR-detectable deficits of acute EAE, and may therefore be a promising therapeutic agent in multiple sclerosis (MS).


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , Integrina alfa4/metabolismo , Enfermedad Aguda , Animales , Anticuerpos/farmacología , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/patología , Sistema Nervioso Central/patología , Medios de Contraste , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Gadolinio DTPA , Cobayas , Integrina alfa4/inmunología , Imagen por Resonancia Magnética/métodos , Índice de Severidad de la Enfermedad
16.
J Neuroimmunol ; 167(1-2): 53-63, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16095724

RESUMEN

Inhibition of alpha(4)beta(1) integrin blocks immune cell influx into the CNS providing benefit to patients with multiple sclerosis and in animal model systems. We have used this mechanism to examine whether the presence of inflammatory cells suppresses spontaneous myelin repair in experimental autoimmune encephalomyelitis. We observed (1) 87% of plaques showed remyelination after 40 days of treatment; (2) myelin repair occurred in half of the total lesion area; (3) half of the animals regained motor function. There was no significant repair or gain of motor function in vehicle-treated animals. Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination.


Asunto(s)
Encefalomielitis Autoinmune Experimental/fisiopatología , Integrina alfa4/fisiología , Vaina de Mielina/metabolismo , Regeneración Nerviosa/fisiología , Recuperación de la Función , Animales , Antiinflamatorios/sangre , Antiinflamatorios/uso terapéutico , Enfermedad Crónica , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Femenino , Cobayas , Inmunohistoquímica/métodos , Actividad Motora/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Médula Espinal/fisiopatología , Linfocitos T/efectos de los fármacos , Factores de Tiempo
17.
Intern Med J ; 35(6): 331-5, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15892761

RESUMEN

BACKGROUND: Matrix metalloproteinases (MMP-9 and MMP-2) have been implicated in development of atherosclerosis and plaque rupture in acute coronary syndromes (ACS). AIM: To determine the relationship between circulating MMPs and symptomatic coronary artery disease. METHODS: Plasma levels of MMP-9 and MMP-2 were measured in patients with ACS, stable angina (SA) and in controls, using a quantitative gelatin zymography. These measurements were correlated with markers of systemic inflammation (hs-CRP) in all subjects and myocardial injury (troponin T) in patients with ACS. RESULTS: Plasma MMP-9 in ACS was greater than in SA, and was greater in SA than in controls (P < 0.01 ACS vs SA and controls, P < 0.01 SA vs control). Plasma MMP-2 was significantly greater in ACS than SA or controls (P < 0.01 vs SA and controls). There was strong overall relationship between hs-CRP and MMP-9 (r = 0.65, P < 0.0001) driven by a significant relationship in ACS patients (r = 0.58, P = 0.02), as there was no significant association in SA or controls. A weaker overall correlation was found between hs-CRP and MMP-2 (r = 0.39, P = 0.02), but no significant relationship was present for either of the two patient subgroups or controls. There was no correlation between levels of troponin T and MMP-9, MMP-2 or hs-CRP in ACS patients. CONCLUSION: Quantitative gelatin zymography identifies increased circulating levels of MMP-9 and MMP-2 in patients with symptomatic coronary disease. MMP-9 and MMP-2 are higher in ACS than SA patients and might have use as markers of plaque rupture or instability. The strong relationship between MMP-9 and hs-CRP in ACS patients suggests MMP-9 might be an additional marker and/or consequence of the inflammatory component in ACS.


Asunto(s)
Enfermedad Coronaria/sangre , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Anciano , Angina de Pecho/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Síndrome , Troponina T/sangre
18.
J Neuroimmunol ; 131(1-2): 147-59, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12458046

RESUMEN

CNS leukocytic invasion in experimental allergic encephalomyelitis (EAE) depends on alpha4beta1 integrin/vascular cell adhesion molecule-1 (VCAM-1) interactions. A small molecule inhibitor of alpha4beta1 integrin (CT301) was administered to guinea pigs in the chronic phase (>d40) of EAE for 10, 20, 30 or 40 days. CT301 elicited a rapid, significant improvement in the clinical and pathological scores that was maintained throughout the treatment period. A progressive loss of cells in the spinal cord of treated animals confirmed the resolution of inflammation associated with clinical recovery. Therefore, prolonged inhibition of alpha4beta1 integrin caused a sustained reversal of disease pathology in chronic EAE and may be similarly useful in MS.


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Integrina alfa4 , Animales , Enfermedad Crónica , Citocinas/biosíntesis , Citocinas/genética , Encefalomielitis Autoinmune Experimental/diagnóstico , Encefalomielitis Autoinmune Experimental/patología , Femenino , Citometría de Flujo , Cobayas , Cinética , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , Médula Espinal/patología
19.
Arch Pediatr Adolesc Med ; 155(12): 1301-6, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11732947

RESUMEN

OBJECTIVE: To determine if, in the era after Haemophilus influenzae type b, the cerebrospinal fluid (CSF) white blood cell (WBC) count can be safely used to stratify children suspected of having bacterial meningitis into low- and high-risk groups. DESIGN: Retrospective analysis of CSF samples. SETTING: Tertiary care pediatric center in Toronto, Ontario, between January 1, 1992, and October 1, 1996. PATIENTS: All CSF samples collected on children aged 2 months to 17 years were included. The final database consisted of 1617 atraumatic samples from children without prior neurologic or immunologic disease who underwent a lumbar puncture to assess the possibility of community-acquired bacterial meningitis. MAIN OUTCOME MEASURES: The predictive values of CSF WBC count, differential, protein, and glucose. RESULTS: There were 44 cases of bacterial meningitis. Five had 3 CSF WBCs per microliter or less, and 6 had 4 to 30 CSF WBCs per microliter. The negative predictive value of CSF specimens with 30 WBCs per microliter or less for bacterial meningitis was 99.3%. Cerebrospinal fluid samples with greater than 30 WBCs per microliter had a likelihood ratio for bacterial meningitis of 10.3 (95% confidence interval, 8.0-13.1) and a positive predictive value of 22.3%. Other significant predictors of bacterial meningitis included age, CSF glucose, protein, gram stain, CSF-serum glucose ratio, and peripheral blood band count. CONCLUSIONS: Given the occurrence of bacterial meningitis in children in the absence of CSF pleocytosis, other factors should be considered when managing children with suspected bacterial meningitis. Children older than 6 months with 30 CSF WBCs per microliter or less are at low risk for bacterial meningitis. If clinically stable and without other laboratory markers of bacterial meningitis, hospital admission and empiric antibiotic therapy may be unwarranted.


Asunto(s)
Recuento de Leucocitos , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Meningitis por Haemophilus/líquido cefalorraquídeo , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Glucosa/líquido cefalorraquídeo , Vacunas contra Haemophilus/uso terapéutico , Humanos , Leucocitosis/líquido cefalorraquídeo , Masculino , Meningitis por Haemophilus/prevención & control , Valor Predictivo de las Pruebas , Análisis de Regresión , Estudios Retrospectivos , Medición de Riesgo , Punción Espinal , Factores de Tiempo
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