RESUMEN
The tumour suppressor PTEN is a key negative regulator of the PI3K-Akt pathway, and is frequently either reduced or lost in human tumours. Murine genetic studies have confirmed that reduction of Pten promotes tumourigenesis in multiple organs, and demonstrated dependency of tumour development on the activation of downstream components such as Akt. Insulin-like growth factors (IGFs) act via IGF1R to activate the PI3K-Akt pathway, and are commonly upregulated in cancer. A context-dependent interplay between IGFs and PTEN exists in normal tissue and tumours; increased IGF2 ligand supply induces Pten expression creating an autoregulatory negative feedback loop, whereas complete loss of PTEN may either cooperate with IGF overexpression in tumour promotion, or result in desensitisation to IGF ligand. However, it remains unknown whether neoplasia associated with Pten loss is dependent on upstream IGF ligand supply in vivo. We evaluated this by generation of Pten(+/-) mice with differing allelic dosage of Igf2, an imprinted gene encoding the potent embryonic and tumour growth factor Igf2. We show that biallelic Igf2 supply potentiates a previously unreported Pten(+/-) placental phenotype and results in strain-dependent cardiac hyperplasia and neonatal lethality. Importantly, we also show that the effects of Pten loss in vivo are modified by Igf2 supply, as lack of Igf2 results in extended survival and delayed tumour development while biallelic supply is associated with reduced lifespan and accelerated neoplasia in females. Furthermore, we demonstrate that reduction of PTEN protein to heterozygote levels in human MCF7 cells is associated with increased proliferation in response to IGF2, and does not result in desensitisation to IGF2 signalling. These data indicate that the effects of Pten loss at heterozygote levels commonly observed in human tumours are modified by Igf2 ligand, and emphasise the importance of the evaluation of upstream pathways in tumours with Pten loss.
Asunto(s)
Transformación Celular Neoplásica/patología , Factor II del Crecimiento Similar a la Insulina/metabolismo , Fosfohidrolasa PTEN/metabolismo , Animales , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Cardiomegalia/genética , Cardiomegalia/metabolismo , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/genética , Femenino , Humanos , Factor II del Crecimiento Similar a la Insulina/genética , Longevidad/genética , Longevidad/fisiología , Masculino , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Ratones , Ratones Endogámicos C57BL , Fosfohidrolasa PTEN/genética , Placenta/citología , Placenta/metabolismo , Embarazo , Factores SexualesRESUMEN
The US Department of Veterans Affairs (VA) cares for many human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients. VA treatment recommendations indicate that all HIV/HCV-coinfected patients undergo evaluation for HCV treatment and list pretreatment assessment tests. We compared clinical practice with these recommendations. We identified 377 HIV/HCV-coinfected veterans who began HCV therapy with pegylated interferon and ribavirin and 4135 HIV/HCV-coinfected veterans who did not but were in VA care at the same facilities during the same period. We compared laboratory and clinical characteristics of the two groups and estimated multivariate logistic regression models of receipt of HCV treatment. Overall, patients had high rates of receipt of tests necessary for HCV pretreatment assessment. Patients starting HCV treatment had higher alanine aminotransferase (ALT), lower creatinine, higher CD4 counts and lower HIV viral loads than patients not starting HCV treatment. In the multivariate model, positive predictors of starting HCV treatment included being non-Hispanic whites, having higher ALTs, lower creatinines, higher HCV viral loads, higher CD4 counts, undetectable HIV viral loads and receiving HIV antiretrovirals. A history of chronic mental illness and a history of hard drug use were negative predictors. Most HIV/HCV-coinfected patients received the necessary HCV pretreatment assessments, although rates of screening for hepatitis A and B immunity can be improved. Having well-controlled HIV disease is by far the most important modifiable factor affecting the receipt of HCV treatment. More research is needed to determine if the observed racial differences in starting HCV treatment reflect biological differences, provider behaviour or patient preference.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Veteranos , Estudios de Cohortes , Femenino , Infecciones por VIH/diagnóstico , Hepatitis C/diagnóstico , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Ribavirina/uso terapéutico , Estados Unidos , United States Department of Veterans AffairsRESUMEN
A quantitative, descriptive survey was conducted using Waterhouse's instrument, Survey of Sexuality-Related Nursing Practice. The purpose of this study was to examine the extent to which maternal/child and women's health nurses address sexuality in their practice and to assess the influence of select variables on that practice. A sample of maternal/child and women's health registered nurses (n = 130) was systematically selected from the 1995 Association of Women's Health, Obstetric and Neonatal Nurses' (AWHONN) District VII mailing list. Findings reveal incongruities in maternal/child and women's health nurses' perspectives and the incorporation of sexuality-related nursing interventions into practice.
Asunto(s)
Actitud del Personal de Salud , Educación Continua en Enfermería/normas , Enfermería Maternoinfantil/educación , Evaluación de Necesidades/organización & administración , Personal de Enfermería en Hospital/educación , Personal de Enfermería en Hospital/psicología , Educación Sexual/normas , Sexualidad , Salud de la Mujer , Adulto , Empleo/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación en Educación de Enfermería , Personal de Enfermería en Hospital/organización & administración , Muestreo , Encuestas y Cuestionarios , Estados UnidosRESUMEN
This article reports on preliminary impacts during the first year of a demonstration in which home health agencies (HHAs) were paid a prospectively set rate for each Medicare home health visit rendered, rather than being reimbursed for costs. Forty-seven agencies in five States participated. The evaluation compared the experiences of randomly assigned treatment agencies and their patients with those of control agencies and their patients and found no compelling evidence of any demonstration impact on agency cost per visit, the volume of home health services, agency revenue and profit, patient selection and retention, quality of care, or use and cost of Medicare services.
Asunto(s)
Agencias de Atención a Domicilio/economía , Medicare/economía , Sistema de Pago Prospectivo/tendencias , Costos y Análisis de Costo , Recolección de Datos , Estudios de Evaluación como Asunto , Investigación sobre Servicios de Salud , Agencias de Atención a Domicilio/estadística & datos numéricos , Medicare/estadística & datos numéricos , Método de Control de Pagos/métodos , Análisis de Regresión , Reembolso de Incentivo/estadística & datos numéricos , Reproducibilidad de los Resultados , Estados UnidosRESUMEN
Bacterial chemotaxis, the directed movement of a cell population in response to a chemical gradient, plays a critical role in the distribution and dynamic interaction of bacterial populations in nonmixed systems. Therefore, in order to make reliable predictions about the migratory behavior of bacteria within the environment, a quantitative characterization of the chemotactic response in terms of intrinsic cell properties is needed.The design of the stopped-flow diffusion chamber (SFDC) provides a well-characterized chemical gradient and reliable method for measuring bacterial migration behavior. During flow through the chamber, a step change in chemical concentration is imposed on a uniform suspension of bacteria. Once flow is stopped, diffusion causes a transient chemical gradient to develop, and bacteria respond by forming a band of high cell density which travels toward higher concentrations of the attractant. Changes in bacterial spatial distributions observed through light scattering are recorded on photomicrographs during a 10-min period. Computer-aided image analysis converts absorbance of the photographic negatives to a digital representation of bacterial density profiles. A mathematical model (part II) is used to quantitatively characterize these observations in terms of intrinsic cell parameters: a chemotactic sensitivity coefficient, chi(0), from the aggregate cell density accumulated in the band and a random motility coefficient, mu, from population dispersion in the absence of a chemical gradient.Using the SFDC assay and an individual-cell-based mathematical model, we successfully determined values for both of these population parameters for Escherichia coli K12 responding to fucose. The values obtained were mu = 1.1 +/- 0. 4 x 10(-5) cm(2)/s and chi(o) = 8 +/- 3 +/- 10(-5) cm(2)/s. We have demonstrated a method capable of determining these parameter values from the now validated mathematical model which will be useful for predicting bacterial migration in application systems.
RESUMEN
The directed movement of a bacterial population in response to a chemical gradient is known as bacterial chemotaxis and plays a critical role in the distribution and dynamic interaction of bacterial populations. A quantitative characterization of the chemotactic response in terms of intrinsic cell properties is necessary for making reliable predictions about the migratory behavior of bacterial populations within the environment.The design of the stopped-flow diffusion chamber (SFDC) provides a well-characterized chemical gradient and reliable method for measuring bacterial migration behavior. During flow through the chamber a step change in the chemical concentration is imposed on a uniform suspension of bacteria. Once flow is stopped a transient chemical gradient forms due to diffusion; bacteria respond by forming a band of high cell density that travels toward higher concentrations of the attractant. Sequential observations of bacterial spatial distributions over a period of about ten minutes are recorded on photomicrographs. Computer-aided image analysis of the photographic negatives converts light-scattering information to a digital representation of the bacterial density profiles. A mathematical model is used to quantitatively characterize these observations in terms of intrinsic cell parameters: a chemotactic sensitivity coefficient, χ0, from the aggregate cell density accumulated in the band and a random motility coefficient, µ0, from population dispersion in the absence of a chemical gradient.Using the SFDC assay and an individual cell-based mathematical model we successfully determined values for both of these population parameters forEscherichia coli K12 responding to fucose. The values we obtained were µ0=1.1 ± 0.4 x 10(-5) cm(2)/sec and χ0=8 ± 3 x 10(-5) cm(2)/sec. These parameters will be useful for predicting population behavior in application systems such as biofilm development, population dynamics of genetically-engineered bacteria released into the environment, and in situ bioremediation technologies.
RESUMEN
The channeling demonstration involved provision of comprehensive case management and direct service expansion. This article considers the former. Under both models, comprehensive case management was implemented largely as intended; moreover, channeling substantially increased the receipt of comprehensive care management. However, channeling was not a pure test of the effect of comprehensive case management: roughly 10-20 percent of control group members received comparable case management services. This was particularly the case for the financial control model. Thus, the demonstration was not a test of case management compared to no case management; rather, it compared channeling case management to the existing community care system, which already was providing comprehensive case management to some of the population eligible for channeling.