RESUMEN
Acute coronary syndromes (ACS) are associated with inflammation resulting from monocyte activation. We sought for differences in the production of pro- and anti-inflammatory cytokines by monocytes from patients with ACS. C-reactive protein (CRP) and neopterin were measured in 22 patients with acute coronary syndromes, 50 patients with stable vascular disease and 22 healthy controls. Production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 was determined after, respectively, 6 and 24 h of incubation of full blood with lipopolysaccharide (LPS). Levels of CRP [median, interquartile range (IQR)][1.5 mg/l (0.8-4.5) ACS patient versus 2.1 (0.9-3.6) stable disease versus 0.4 (0.3-1.2) healthy controls] (P < 0.001) and neopterin [7.4 nmol/l (6.0-8.7) ACS patient versus 7.1(6.0-8.9) stable disease versus 6.4 (5.6-7.3) healthy controls] (P = 0.07) were higher in both the patient groups. IL-10 production after LPS stimulation was greatly reduced in patients with acute coronary syndromes (16 175 pg/ml, 7559-28 470 pg/ml) as opposed to patients with stable disease (28 379 pg/ml, 12 601-73 968 pg/ml) and healthy controls (63 830 pg/ml, 22 040-168 000 pg/ml) (P = 0.003). TNF-alpha production was not signi fi cantly different between the groups [7313 pg/ml (4740-12 615) ACS patient versus 11 002 (5913-14 190) stable disease versus 8229 (5225-11 364) healthy controls] (P = 0.24). Circulating monocytes in unstable coronary syndromes produce equal amounts of TNF-alpha but less IL-10 after stimulation with LPS in vitro as compared with healthy controls. We hypothesize that, in acute coronary syndromes, the production proinflammatory cytokines is not counterbalanced by anti-inflammatory cytokines such as IL-10.
Asunto(s)
Angina Inestable/inmunología , Interleucina-10/biosíntesis , Lipopolisacáridos/inmunología , Monocitos/inmunología , Infarto del Miocardio/inmunología , Adulto , Anciano , Angina Inestable/metabolismo , Recuento de Células Sanguíneas , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/metabolismo , Femenino , Humanos , Interleucina-10/inmunología , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Infarto del Miocardio/metabolismo , Neopterin/sangre , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
OBJECTIVES: Creatinine clearance (CCR) is a commonly used tool to measure glomerular filtration rate (GFR) in clinical practice. This tool requires collection of 24-h urine, which is quite bothersome. Several different formulae have been used to estimate GFR using plasma creatinine and other easy formulae to obtain biometrical data. We examined 10 formulae and compared them with actually measured CCR in a large sample of the general population. DESIGN: Cross-sectional cohort study. SETTING: University hospital outpatient clinic, a population based study. SUBJECTS: A total of 8592 inhabitants of the city of Groningen, 28-75 years of age. The cohort is enriched for microalbuminuria. RESULTS: In general, the formulae did not give an accurate estimation of CCR, particularly not in male and in obese subjects. Six formulae, including the Cockcroft-Gault gave a fairly good estimation of CCR in the overall population and in subgroups of specific gender, body mass index and age. All formulae however, gave an underestimation of the measured CCR in higher ranges of CCR and an overestimation in the lower ranges. Moreover, the age-related decline of CCR is hard to approximate with a formula. CONCLUSIONS: We conclude that formulae to estimate CCR in the general population, although giving a fairly good estimate of mean CCR, do not offer reliable data on CCR in the upper and lower ranges and do not adequately estimate the age-related decline in CCR.
Asunto(s)
Algoritmos , Creatinina/sangre , Creatinina/orina , Tasa de Filtración Glomerular , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Platelet deposition and aggregation are the major determinants of acute thrombosis in coronary stents. We aimed to compare the antiplatelet efficacy of different treatments--glycoprotein (Gp) IIb/IIIa inhibitors and conventional antiaggregants--in an experimental model for stenting. Blood samples were obtained from patients with coronary artery disease (n = 15) and healthy volunteers (n = 8) and incubated either with eptifibatide (2.0 microg/ml), abciximab (3.0 microg/ml), indomethacin (15 microg/ml), or saline. Platelet adenosine diphosphate-induced aggregation in whole blood was assessed for all groups. Blood was also tested in an experimental circulation model containing metallic probes, on which platelet deposition in shear flow conditions was assessed by means of fluorescent-labeled platelet-specific (anti-GpIIIa and Ib) antibodies. Eptifibatide and abciximab, in comparison with indomethacin and no treatment, significantly reduced platelet aggregation (0, 0, 4, and 3 arbitrary units [AU], respectively; p < 0.001), anti-GpIIIa (2.25, 1.83, 11.24, and 13.42 counts per second [cps]/mg, respectively; p < 0.001), and anti-GpIb binding (0.61, 0.61, 1.00, and 1.83 cps/mg, respectively; p < 0.001). Anti-GpIIIa and anti-GpIb binding were significantly correlated (R = 0.36; p < 0.01). Patients showed a higher anti-GpIIIa, but not anti-GpIb binding, than controls (8.43 versus 3.33 cps/mg; p < 0.01), irrespective of treatment. In conclusion, eptifibatide and abciximab show equivalent in vitro antiplatelet efficacy, superior to that of indomethacin. Given the occurrence of GpIIb/IIIa platelet overexpression in the course of coronary artery disease, an extended use of GpIIb/IIIa inhibitors may be proposed to prevent acute thrombosis during routine coronary stenting.