RESUMEN
Interleukins -4, -5, and -13, cardinal cytokines produced by Th2 cells, are coordinately expressed and clustered in 150-kb syntenic regions on mouse chromosome 11 and human chromosome 5q31. We analyzed two sets of human yeast artificial chromosome transgenic mice that contained the 5q31 cytokines to assess whether conserved sequences required for their coordinate and cell-specific regulation are contained within the cytokine cluster itself. Human IL-4, IL-13, and IL-5 were expressed under Th2, but not Th1, conditions in vitro. Each of these cytokines was produced during infection with Nippostrongylus brasiliensis, a Th2-inducing stimulus, and human IL-4 was generated after activation of NK T cells in vivo. Consistently fewer cells produced the endogenous mouse cytokines in transgenic than in control mice, suggesting competition for stable expression between the mouse and human genes. These data imply the existence of both conserved trans-activating factors and cis-regulatory elements that underlie the coordinate expression and lineage specificity of the type 2 cytokine genes in lymphocytes.
Asunto(s)
Cromosomas Humanos Par 5/inmunología , Citocinas/biosíntesis , Citocinas/genética , Regulación de la Expresión Génica/inmunología , Familia de Multigenes , Transgenes/inmunología , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Cromosomas Humanos Par 5/genética , Citocinas/administración & dosificación , Citocinas/fisiología , Humanos , Interleucina-4/biosíntesis , Líquido Intracelular/inmunología , Líquido Intracelular/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Subgrupos Linfocitarios/citología , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Microinyecciones , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/inmunología , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
A prospective standardized collection of clinical, microbiological and pharmaceutical information on antibiotic use was conducted in Australia and New Zealand intensive care units (ICUs) involving 481 consecutive critically ill patients who were receiving antibiotics for any reason while in ICU. Patients had a mean SAPS II score of 34.1 +/- 17.8 with an expected mortality of 15.6% (actual mortality 12%). Of these, 292 (60.8%) were admitted to the ICU within 72 hours of surgery. Among such surgical patients, 233 (79.9%) received antibiotics for "surgical prophylaxis" while in ICU (48% of sample population). The second largest group of patients treated with antibiotics in ICU included those with systemic inflammatory response syndrome and clinical suspicion of infection (38%). Antibiotics were prescribed for the treatment of clinically diagnosed infection in 268 patients. Clinical response was apparent in 62.6% and in most (71%) was achieved in the first 72 hours of treatment. The incidence of antimicrobial-related side-effects was 4%, mostly in the form of diarrhoea or rash (75% of all side-effects). The most commonly prescribed antimicrobials were gentamicin (n = 146), ceftriaxone (n = 98), vancomycin (n = 94) and metronidazole (n = 111). Three times daily prescription of aminoglycosides was uncommon (< 1%). Forty-one patients had a documented infection (positive culture) with a gram-negative organism. Of these, 17 received therapy with a single antibiotic and 24 received therapy with two antibiotics. Despite similar illness severity, there were six deaths in the former group and only two in the latter.
Asunto(s)
Antibacterianos/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Profilaxis Antibiótica/estadística & datos numéricos , Australia , Enfermedad Crítica , Utilización de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Estudios ProspectivosRESUMEN
OBJECTIVE: To compare the effects of opioid and non-opioid sedation on gastric emptying. DESIGN: Prospective, randomized trial. SETTING: University teaching hospital ICU. PATIENTS: 21 brain injured patients requiring sedation, mechanical ventilation and intracranial pressure (ICP) monitoring for > 24 h. INTERVENTIONS: Patients were randomized to receive infusions of either morphine plus midazolam (M), or propofol (P). Gastric emptying was assessed by the paracetamol absorption technique and by residual volumes following a 200 ml test feed. MEASUREMENTS AND RESULTS: Pre-sedation Glasgow Coma Score, mean ICP and the presence of bowel sounds were noted. Plasma concentrations of paracetamol were measured over 3 h following a 1 g gastric dose. There were no differences in median peak paracetamol concentration (M, 18.5 versus P, 20.8 mg/l), median time to peak concentration (M, 20 versus P, 25 min), median area under the concentration-time curve (AUC), or in the median residual volumes at 1 h (M, 14 versus P, 10.5 ml) and 2 h (M, 5 versus P, 3 ml). In patients with ICP > 20 mmHg, paracetamol concentrations were lower (p < 0.05), and AUC after 30 min was lower (165 mg.min/l versus 411 mg.min/l, p = 0.023). Mean ICP was correlated with AUC (Kendall rank p = 0.027). Gastric emptying did not correlate with initial Glasgow Coma Score or presence of bowel sounds. CONCLUSIONS: Gastric emptying is not improved in patients with brain injury by avoiding morphine (1-8 mg/h) in the sedative regimen. Intracranial hypertension is associated with reduced gastric emptying.
Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/fisiopatología , Sedación Consciente/métodos , Vaciamiento Gástrico/efectos de los fármacos , Seudotumor Cerebral/fisiopatología , Acetaminofén/farmacocinética , Adulto , Lesiones Encefálicas/complicaciones , Quimioterapia Combinada , Femenino , Humanos , Hipnóticos y Sedantes/farmacología , Masculino , Midazolam/farmacología , Persona de Mediana Edad , Morfina/farmacología , Narcóticos/farmacología , Propofol/farmacología , Estudios Prospectivos , Seudotumor Cerebral/etiologíaAsunto(s)
Torsión del Cordón Espermático/cirugía , Medicina Submarina , Adulto , Humanos , MasculinoRESUMEN
Thirty-one patients with proven acute myocardial infarction (MI) were studied prospectively at the time of admission to hospital and at 3, 7 and 18 days using 4 immune complex (IC) assays. Each assay showed an increased incidence of IC activity in MI with 76% of patients being positive in at least 1 assay on one or more of the sampling days. A positive IC assay did not show a significant correlation with cardiac failure, pericarditis, post MI syndrome or previous infarction. The presence of IC was found to correlate with serum C-reactive protein (CRP), serum enzymes and ESR and suggested that complexed CRP or other acute phase proteins may account for some of the IC activity found with less specific assays. The measurement of IC levels in MI has not proved helpful in the diagnosis, management or prediction of outcome in this disorder.