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Sulfametazina/sangre , Sulfatiazoles/sangre , Sulfisomidina/sangre , Administración Oral , Animales , Pruebas de Función Renal , Cinética , Masculino , Modelos Biológicos , Unión Proteica , Conejos , Sulfametazina/orina , Sulfatiazoles/orina , Sulfisomidina/orina , Factores de Tiempo , Agua/administración & dosificación , Agua/farmacologíaAsunto(s)
Compuestos de Anilina/sangre , Naftalenos/sangre , Ácidos Sulfónicos/sangre , Aminas/administración & dosificación , Aminas/sangre , Aminas/orina , Compuestos de Anilina/administración & dosificación , Compuestos de Anilina/orina , Animales , Inyecciones Intravenosas , Inulina/administración & dosificación , Inulina/sangre , Cinética , Masculino , Modelos Biológicos , Naftalenos/administración & dosificación , Naftalenos/orina , Unión Proteica , Conejos , Ácidos Sulfónicos/administración & dosificación , Ácidos Sulfónicos/orina , Factores de TiempoRESUMEN
OBJECTIVE: To ascertain the incidence, severity, risk factors, and outcomes of injuries in children and adolescents playing Australian Rules football. SETTING AND SUBJECTS: A prospective cohort study of football injuries in children and adolescents playing community football. We studied a stratified random sample of 54 teams and clinics (18 under-15 teams, 18 under-10 teams and 18 Vickick clinics for children under 10 years) from the Melbourne metropolitan area. Football exposure, injuries and associated risk factors were recorded for 1253 players during the 1992 football season. RESULTS: Vickick, a modified form of the game, had the lowest rates of injury for all levels of injury severity, with an overall rate of 3.49 injuries per 1000 player-hours. The rate in the under-10 age group was 2.4 times higher (95% confidence interval [CI], 1.5-3.8) than that in Vickick, and the under-15 rate was 1.2 times (95% CI, 0.9-1.6) that of the under-10s. The under-15 age group had significantly more injuries that led to use of health services than the under-10 and Vickick groups, with rates of 3.93 (95% CI, 2.9-4.9), 0.64 (95% CI, 0.2-1.4), and 0.33 (95% CI, 0.1-0.8) injuries per 1000 players-hours respectively. Injuries were largely to soft tissues (sprains 26%, haematomas 25%) and to the lower limb (43%). Very few serious injuries occurred (19 fractures and three injuries with loss of consciousness); nearly all of these were in the under-15s. Rule modifications in under-10 teams and clinics were associated with an injury rate of 5.8 injuries per 1000 player-hours (95% CI, 4.4-7.3) compared with 7.5 injuries per 1000 player-hours (95% CI, 5.2-9.8) when no modification was used. Alterations to the ruck contest, decreased contact, field size and player numbers were significantly associated with lower injury rates, while body size was not. Of the 30% of injuries resulting in a health service consultation, the most common health provider was a medical practitioner. Very few required expensive investigation or treatment. CONCLUSION: Injury rates were low in children under age 10, but higher in adolescents. Most injuries were minor, and did not result in a health professional consultation. Rule modifications were associated with substantially lower injury rates at the under-10 level, and should be promoted as a safe way to learn football skills.
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Fútbol/lesiones , Adolescente , Factores de Edad , Traumatismos del Brazo/epidemiología , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología , Conmoción Encefálica/epidemiología , Niño , Estudios de Cohortes , Femenino , Fracturas Óseas/epidemiología , Hematoma/epidemiología , Humanos , Incidencia , Traumatismos de la Pierna/epidemiología , Masculino , Estudios Prospectivos , Factores de Riesgo , Estaciones del Año , Fútbol/legislación & jurisprudencia , Esguinces y Distensiones/epidemiología , Factores de Tiempo , Victoria/epidemiologíaRESUMEN
It has been claimed that low protein diets slow deterioration of chronic renal failure (CRF) by reducing renal solute load. The anabolic effect of recombinant human growth hormone (rhGH) also has potential to reduce renal solute load and thereby slow progression of renal failure. The aim of this study was to determine the effect of rhGH on growth, renal solute load and renal function in children with CRF. Seven prepubertal children, aged 2-14 years, with moderately severe CRF (creatinine clearance 7.7-23.4 mL/min per 1.73m2) were treated with daily subcutaneous rhGH, 1 U/kg per week for 10-12 months. As expected, mean height velocity standard deviation scores (SDS) increased, from -2.87 before treatment to +3.39 on rhGH, and mean height increased from -3.1 to -2.4 SDS. Serum urea concentrations decreased in most patients during the first month of growth hormone treatment from a mean of 20.0 +/- 7.7 mmol/L to 14.8 +/- 5.8 mmol/L (P = 0.006). The serum urea then returned to pretreatment levels over the next few months. In the 12 months before treatment with growth hormone, mean creatinine clearance decreased from 19.3 mL/min per 1.73 m2 to 16.7 mL/min per 1.73 m2. In the next 12 months on rhGH mean creatinine clearance decreased further to 13.5 mL/min per 1.73 m2. Therefore the rate of deterioration of renal function was unaffected during treatment with growth hormone. Initial treatment with rhGH is associated with decrease in serum urea concentrations in children with CRF, probably mediated by stimulation of anabolic incorporation of dietary nitrogen into body protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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Nitrógeno de la Urea Sanguínea , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/tratamiento farmacológico , Adolescente , Estatura/efectos de los fármacos , Niño , Preescolar , Creatinina/sangre , Creatinina/metabolismo , Creatinina/orina , Femenino , Trastornos del Crecimiento/etiología , Hormona del Crecimiento/farmacología , Humanos , Inyecciones Subcutáneas , Fallo Renal Crónico/clasificación , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/orina , Masculino , Índice de Severidad de la EnfermedadRESUMEN
A formalised system of adverse drug reaction (ADR) reporting was instituted at the Royal Adelaide Hospital in August 1975. The present report reviews the results obtained from this system after a 12-month period of operation. A significant number of reports associated with the use of antibiotics and radiographic contrast media were received. The importance of "feed-back" of ADR information to prescribers is emphasised.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hospitales , Antibacterianos/efectos adversos , Australia , Medios de Contraste/efectos adversos , HumanosRESUMEN
M1 myeloid cells transfected with the wild-type (WT) colony-stimulating factor-1 (CSF-1) receptor (CSF-1R; M1/WT cells) undergo CSF-1-dependent macrophage differentiation. By mutation studies, we have provided prior evidence that tyrosine 559 in the CSF-1R cytoplasmic domain governs the Src-dependent differentiation pathway. Further components of this pathway were then sought. We report that the extent of CSF-1-mediated tyrosine phosphorylation of protein phosphatase 2A (PP2A), and the associated loss of its activity were reduced in M1 cells transfected with the CSF-1R with a tyrosine-to-phenylalanine mutation at position 559 (M1/559 cells), compared with the corresponding responses in CSF-1-treated M1/WT cells. This evidence for an involvement of a reduction in PP2A activity in the differentiation process was supported by the restoration of the defect in the CSF-1-mediated differentiation of M1/559 cells by the addition of the PP2A inhibitor, okadaic acid. It was also found that the degree of activation of extracellular-signal-regulated kinase (ERK) activities by CSF-1 was reduced in M1/559 cells, suggesting their involvement in the differentiation process. These data suggest that PP2A and ERK form part of the Src-dependent signal-transduction cascade governing CSF-1-mediated macrophage differentiation in M1 cells.
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Macrófagos/fisiología , Células Mieloides/citología , Fosfoproteínas Fosfatasas/metabolismo , Receptor de Factor Estimulante de Colonias de Macrófagos/química , Receptor de Factor Estimulante de Colonias de Macrófagos/fisiología , Animales , Diferenciación Celular , Línea Celular , Inhibidores Enzimáticos/farmacología , Macrófagos/citología , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutación , Células Mieloides/efectos de los fármacos , Ácido Ocadaico/farmacología , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosforilación , Fosfotirosina/metabolismo , Proteína Fosfatasa 2 , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Transducción de SeñalRESUMEN
Using two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS-PAGE) of 32P-labeled cytosolic and membrane extracts, we identified a 21.5 kDa phosphoprotein with an isoelectric point of 6.0 in NFS-60 cells that was phosphorylated maximally at 15 min by treatment with granulocyte-colony stimulating factor (G-CSF) but not with interlevkin-3 (IL-3) or colony-stimulating factor-1 (macrophage-colony stimulating factor (CSF-1 (M-CSF)). The phosphorylation of this protein, designated 21.5/6.0, was unaffected by a series of antiproliferative agents [32]. These findings suggested that the 21.5/6.0 phosphoprotein may be involved in specific G-CSF-mediated biological responses such as activation and/or differentiation. We sought to characterize this 21.5/6.0 by a novel combination of 2-D SDS-PAGE and hydroxyapatite (HTP)-chromatography. Amino acid sequence determination of 21.5/6.0 revealed it to share a high level of homology with copper/zinc superoxide dismutase (Cu/Zn-SOD), indicating that a Cu/Zn-SOD is phosphorylated following treatment with G-CSF. This is the first report of the phosphorylation and possible involvement of Cu/Zn-SOD protein in granulocyte activation/differentiation events. In addition, Cu/Zn-SOD levels and activity were diminished by G-CSF but not IL-3 treatment. This new protocol combining 2-D SDS-PAGE and HTP-chromatography allows the characterization of low abundance phosphoproteins involved in the cellular responses to G-CSF and presumably to other cytokines/growth factors.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Superóxido Dismutasa/química , Superóxido Dismutasa/efectos de los fármacos , Animales , Línea Celular , Cromatografía , Durapatita , Electroforesis en Gel Bidimensional , Interleucina-3/farmacología , Punto Isoeléctrico , Ratones , Peso Molecular , Fosfoproteínas/química , Fosfoproteínas/efectos de los fármacos , Fosfoproteínas/aislamiento & purificación , Fosforilación , Proteoma , Superóxido Dismutasa/aislamiento & purificaciónRESUMEN
Macrophage colony stimulating factor (M-CSF or CSF-1) acts to regulate the development and function of cells of the macrophage lineage. Murine myeloid FDC-P1 cells transfected with the CSF-1 receptor (FD/WT) adopt a macrophage-like morphology when cultured in CSF-1. This process is abrogated in FDC-P1 cells transfected with the CSF-1 receptor with a tyrosine to phenyalanine substitution at position 807 (FD/807), suggesting that a molecular interaction critical to differentiation signaling is lost (Bourette, R. P., Myles, G. M., Carlberg, K., Chen, A. R., and Rohrschneider, L. R. (1995) Cell Growth Differ. 6, 631--645). A detailed examination of lysates of CSF-1-treated FD/807 cells by two-dimensional SDS-polyacrylamide gel electrophoresis (PAGE) revealed a number of proteins whose degree of tyrosine phosphorylation was modulated by the Y807F mutation. Included in this category were three phosphorylated proteins that co-migrated with p46/52(Shc). Immunoprecipitation, Western blotting, and in vitro binding studies suggest that they are indeed p46/52(Shc). A key regulator of differentiation in a number of cell systems, ERK was observed to exhibit an activity that correlated with the relative degree of differentiation induced by CSF-1 in the two cell types. Transfection of cells with a non-tyrosine-phosphorylatable form of p46/52(Shc) prevented the normally observed CSF-1-mediated macrophage differentiation as determined by adoption of macrophage-like morphology and expression of the monocyte/macrophage lineage cell surface marker, Mac-1. These results are the first to suggest that p46/52(Shc) may play a role in CSF-1-induced macrophage differentiation. Additionally, a number of proteins were identified by two-dimensional SDS-PAGE whose degree of tyrosine phosphorylation is also modulated by the Y807F substitution. This group of molecules may contain novel signaling molecules important in macrophage differentiation.