RESUMEN
Although poor nutritional status and weight loss in cancer patients is known to affect outcomes, little is known about malnutrition differences based on geographic location. We investigated nutritional and inflammatory status of 220 newly diagnosed adults with solid tumors at the University of Kentucky's Markey Cancer Center during December 2008 through October 2011. Chi-square tests were used to determine any associations between suboptimal nutritional levels and rural-urban areas of residence. Out of the 13 lab values collected, the only significant difference between rural and urban participants was found for vitamin D resulting in more rural subjects (67.4%) having a suboptimal vitamin D status as compared to those residing in urban areas (53.3%, P = 0.04). Controlling for baseline demographics including age, race, sex, body mass index, nutritional status, and type of cancer, logistic regression analyses concluded those in rural areas had nearly a twofold increase in the odds of having a suboptimal vitamin D level compared to those in urban areas (odd's ratio = 1.97; 95% confidence interval = 1.04, 3.74). Further investigation into the rural-urban differences in vitamin D needs to be investigated in order to improve outcomes during cancer treatment.
Asunto(s)
Neoplasias/sangre , Estado Nutricional , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Kentucky/epidemiología , Modelos Logísticos , Masculino , Micronutrientes/sangre , Micronutrientes/deficiencia , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Oportunidad Relativa , Prevalencia , Población Rural , Factores Socioeconómicos , Encuestas y Cuestionarios , Población Urbana , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/sangreRESUMEN
OBJECTIVE: To quantify the set-up costs and monetary benefits of a welfare rights service integrated within an NHS service provider, that selects eligible patients using the Health Assessment Questionnaire (HAQ) and offers welfare rights advice to assist in application for Disability Living Allowance and Attendance Allowance. METHOD: (1) DESIGN: a cost evaluation of a social intervention, screening with the HAQ and welfare rights advice in primary care and hospital settings. (2) SETTING: Eight general practices and four hospital rheumatology out-patient departments were selected from four localities in the southwest of England. (3) PARTICIPANTS: Two hundred and sixty-eight eligible patients with arthritis accepted an interview with a welfare rights officer (WRO) from a sample of 1989 service users identified from GPs' records and hospital out-patient lists. Two hundred and forty two service users expressed an interest in take up of the social intervention. (4) Service users with a HAQ score >/=1.5 were contacted by telephone and offered an appointment with an experienced WRO to help them complete a welfare benefit application form. A 'micro-costing' study was undertaken with assessment of monetary benefits received. RESULTS: The indicative set-up costs of similar welfare rights services are pound 8125 in a GP setting and pound 9307 per annum in a hospital setting at 2002 prices. Total annual unclaimed Disability Living Allowance/Attendance Allowance granted to successful claimants was pound 184,382 in the GP setting (n = 84 from 137) and pound 169,309 in the hospital setting (n = 79 from 131). CONCLUSIONS: Welfare rights advice received during a visit to a GP practice or a hospital out-patient department can substantially reduce the level of unclaimed benefit in arthritic populations including the elderly; with mobility and care difficulties. A welfare rights service integrated within a GP practice or hospital that screens people with arthritis using HAQ scores and encourages those with scores >/=1.5 to see a WRO for help with welfare benefit confers monetary benefits for service users that substantially outweigh set-up costs.
Asunto(s)
Artritis/economía , Seguridad Social/economía , Anciano , Atención Ambulatoria/economía , Artritis Reumatoide/economía , Costos y Análisis de Costo/métodos , Prestación Integrada de Atención de Salud/economía , Inglaterra , Medicina Familiar y Comunitaria/economía , Femenino , Humanos , Masculino , Osteoartritis/economía , Medicina Estatal , Encuestas y CuestionariosRESUMEN
This paper reviews the literature on younger people (under 65 years of age) with dementia, in dementia care. Seventy-four relevant papers were identified by use of a search strategy derived from the methodology of systematic reviews, the majority of which originated in the UK (69, 93.2%). The need for specialist, flexible, age-appropriate, and dedicated services was a central theme in the literature. A person-centred approach was advocated within an individual or 'tailor made' model of care. However, the available evidence suggests that this model of good practice is not currently reflected in the majority of services provided in the United Kingdom. Overall, the literature argues that the needs of younger people with dementia are best served by inter-agency collaboration, early assessment, and an awareness of individual needs. Clearly, these proposals could usefully serve anybody with dementia, irrespective of age. However, aside from a few prevalence studies, and some exploratory work with small numbers of service users, little in the way of empirical work is available. The recommendations that have been made regarding dementia services for younger people are based largely on the practical experience of professionals and paid carers, rather than scientific evidence.
Asunto(s)
Benchmarking/tendencias , Demencia/rehabilitación , Necesidades y Demandas de Servicios de Salud/tendencias , Medicina Estatal/tendencias , Adulto , Anciano , Demencia/epidemiología , Demencia/etiología , Predicción , Humanos , Persona de Mediana Edad , Grupo de Atención al Paciente/tendencias , Reino UnidoRESUMEN
To establish lifelong infection in the presence of an active host immune system, herpesviruses have acquired an impressive array of immune modulatory mechanisms that contribute to their success as long-term parasites. Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV has acquired a battery of genes to assist in viral survival against the host immune response. These viral gene products target a variety of host immune surveillance mechanisms, including the cytokine-mediated immune response, apoptosis, natural killer (NK) cell killing and T cell-mediated responses. This review summarizes our understanding of the role of these viral proteins in the escape from host immune surveillance, which ultimately contributes to lifelong infection and pathogenesis of KSHV.
Asunto(s)
Infecciones por Herpesviridae/inmunología , Herpesvirus Humano 8/inmunología , Animales , Apoptosis , Citocinas , Genes Virales , Herpesvirus Humano 8/genética , Humanos , Inmunidad Activa/genética , Inmunidad Innata/genética , Interferones , Células Asesinas Naturales , Linfocitos T Citotóxicos , Proteínas Virales/inmunología , Replicación ViralRESUMEN
Sixty-seven English language articles were obtained for the review, the majority of which (44, 65.7%) had US origins. Broadly, the main issues covered in the literature were the under-utilization of services by minority ethnic groups; the prevalence of dementia in different ethnic groups; the experience of care giving in different racial groups and language as a factor in cognitive assessment. Although it has been argued that the instruments used to assess cognitive function are culturally biased, the available published evidence would seem to suggest that the fundamental issue is language ability, rather than minority group membership per se. Studies into the care giving experience amongst different ethnic or racial groups suffer from theoretical and methodological weaknesses. Studies of help-seeking among various ethnic groups in the US have found that many do not prioritize dementia as a health problem in the face of more pressing concerns. There was little consensus amongst the articles about whether services should be provided specifically for different ethnic groups, reflecting a lack of evidence concerning the efficacy of different models of service provision.
Asunto(s)
Demencia/etnología , Demencia/terapia , Etnicidad , Necesidades y Demandas de Servicios de Salud , Servicios de Salud para Ancianos/estadística & datos numéricos , Grupos Minoritarios , Anciano , Barreras de Comunicación , Demencia/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud , Humanos , Lenguaje , Guías de Práctica Clínica como AsuntoRESUMEN
West Nile (WN) virus was detected in the metropolitan New York City (NYC) area during the summer and fall of 1999. Sixty-two human cases, 7 fatal, were documented. The New York State Department of Health initiated a departmental effort to implement a statewide mosquito and virus surveillance system. During the 2000 arbovirus surveillance season, we collected 317,676 mosquitoes, submitted 9,952 pools for virus testing, and detected 363 WN virus-positive pools by polymerase chain reaction (PCR). Eight species of mosquitoes were found infected. Our mosquito surveillance system complemented other surveillance systems in the state to identify relative risk for human exposure to WN virus. PCR WN virus-positive mosquitoes were detected in NYC and six counties in the lower Hudson River Valley and metropolitan NYC area. Collective surveillance activities suggest that WN virus can disperse throughout the state and may impact local health jurisdictions in the state in future years.
Asunto(s)
Culicidae/virología , Brotes de Enfermedades , Insectos Vectores/virología , Fiebre del Nilo Occidental/epidemiología , Virus del Nilo Occidental/aislamiento & purificación , Animales , Culicidae/clasificación , ADN Viral/análisis , Humanos , Insectos Vectores/clasificación , New York/epidemiología , Ciudad de Nueva York/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/genética , Virus del Nilo Occidental/inmunologíaRESUMEN
Medical practitioners are encountering more women who are presently or formerly homeless. Homelessness negatively affects health and health outcomes. Women without homes experience repeated violence and trauma. In this review, the definition and scope of homelessness as it impacts women is discussed, from the etiology of women's homelessness to a description of their lifestyle. A paradigm of a primary care approach to understanding and treating women without homes is presented, including strategies for history taking, physical exams, and follow-up care that help build trust and improve compliance.
Asunto(s)
Personas con Mala Vivienda , Servicios de Salud para Mujeres , Continuidad de la Atención al Paciente , Femenino , Personas con Mala Vivienda/estadística & datos numéricos , Humanos , Anamnesis , Examen Físico , Relaciones Médico-Paciente , Atención Primaria de Salud , Estados UnidosRESUMEN
Kaposi's Sarcoma associated Herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV contains numerous open reading frames with striking homology to cellular genes. These viral gene products play a variety of roles in KSHV-associated pathogenesis by disrupting cellular signal transduction pathways, which include interferon-mediated anti-viral responses, cytokine-regulated cell growth, apoptosis, and cell cycle control. In this review, we will attempt to cover our understanding of how viral proteins deregulate cellular signaling pathways, which ultimately contribute to the conversion of normal cells to cancerous cells.
Asunto(s)
Herpesvirus Humano 8/metabolismo , Imitación Molecular , Animales , Apoptosis , Transformación Celular Neoplásica/metabolismo , Evolución Molecular , Genes Virales/genética , Haplorrinos/virología , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/inmunología , Herpesvirus Humano 8/aislamiento & purificación , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virología , Transducción de Señal , Proteínas Virales/genética , Proteínas Virales/inmunología , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail. METHODS: Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. RESULTS: With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset. CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Hierro/administración & dosificación , Diálisis Renal/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/sangre , Anemia Ferropénica/diagnóstico , Eritropoyetina/uso terapéutico , Hospitalización , Humanos , Inyecciones Intravenosas , Hierro/efectos adversos , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
To better define the effects of sequence variation and tropism on the ability of the simian immunodeficiency virus SIVmac V3 loop to act as a target of antibody-mediated neutralization, a series of experiments were performed. Three SIV strains, SIVmac239, SIVmac316, and SIVmac155/T3, each with defined differences in env sequence and tropism, were used to construct a panel of viruses chimeric for a portion of envelope that includes the V2 and V3 regions. Peptides with sequences corresponding to the V3 loops of the parental viruses were used to immunize rabbits. The polyclonal rabbit antibodies and plasma from SIVmac239-infected animals were then used to assess the neutralization sensitivity of the parental and chimeric viruses. One of the parental viruses, SIVmac316, which is able to replicate to high titer in alveolar macrophages and can infect cells in a CD4-independent fashion, was highly sensitive to neutralization by plasma from SIVmac-infected rhesus macaques, with average 50% neutralization titers of 1:20,480; this same strain was also sensitive to neutralization by the anti-V3 loop peptide sera. Other parental and chimeric viruses were less sensitive to neutralization with this same panel of antibodies, but as seen with SIVmac316, those viruses that were able to productively replicate in alveolar macrophages were more sensitive to antibody-mediated neutralization. To further define the amino acids involved in increased sensitivity to neutralization, a panel of viruses was constructed by changing envelope residues in SIVmac316 to the corresponding SIVmac239 amino acids. The increased neutralization sensitivity observed for SIVmac316 was mapped principally to three amino acid changes spread throughout gp120. In addition, the increased sensitivity to neutralization by V3-directed antibodies correlated with the ability of the various viruses to replicate to high levels in alveolar macrophage cultures and a CD4-negative cell line, BC7/CCR5. These results demonstrate that the V3 loop of SIVmac Env can act as an efficient target of neutralizing antibodies in a fashion that is highly dependent on sequence context. In addition, these studies suggest a correlation between decreased dependence on CD4 and increased sensitivity to antibody-mediated neutralization.
Asunto(s)
Anticuerpos Antivirales/inmunología , Antígenos CD4/metabolismo , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/inmunología , Macrófagos/virología , Glicoproteínas de Membrana , Virus de la Inmunodeficiencia de los Simios/crecimiento & desarrollo , Virus de la Inmunodeficiencia de los Simios/inmunología , Proteínas del Envoltorio Viral , Secuencia de Aminoácidos , Animales , Unión Competitiva , Antígenos CD4/análisis , Línea Celular , ADN Recombinante/genética , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/metabolismo , Humanos , Sueros Inmunes/inmunología , Macaca mulatta/virología , Datos de Secuencia Molecular , Mutación/genética , Pruebas de Neutralización , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Conejos , Receptores CCR5/genética , Receptores CCR5/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo , Linfocitos T/virologíaRESUMEN
Stocks of simian immunodeficiency virus (SIV) from the supernatants of infected cell cultures were used to examine the sensitivity of envelope glycoprotein gp120 to enzymatic deglycosylation and the effects of enzyme treatment on infectivity. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and Western blot analysis revealed little or no change in the mobility of virion-associated gp120 after digestion with high concentrations of N-glycosidase F, endoglycosidase F, endoglycosidase H, and endo-beta-galactosidase. Soluble gp120, which was not pelletable after the enzymatic reaction, was sensitive to digestion by the same enzymes within the same reaction mix and was only slightly less sensitive than gp120 that had been completely denatured by boiling in the presence of SDS and beta-mercaptoethanol. Digestion by three of the seven glycosidases tested significantly changed the infectivity titer compared to that of mock-treated virus. Digestion by endo-beta-galactosidase increased infectivity titers by about 2.5-fold, and neuraminidase from Newcastle disease virus typically increased infectivity titers by 8-fold. Most or all of the increase in infectivity titer resulting from treatment with neuraminidase could be accounted for by effects on the virus, not the cells; SIV produced in the presence of the sialic acid analog 2,3-dehydro-2-deoxy-N-acetylneuraminic acid also exhibited increased infectivity, and the effects could not be duplicated by neuraminidase treatment of cells. Digestion with mannosidase reduced infectivity by fivefold. Our results indicate that carbohydrates on native oligomeric gp120 as it exists on the surface of virus particles are largely occluded and are refractory to digestion by glycosidases. Furthermore, the sialic acid residues at the ends of carbohydrate side chains significantly reduce the inherent infectivity of SIV.
Asunto(s)
Glicósido Hidrolasas/metabolismo , Virus de la Inmunodeficiencia de los Simios/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Animales , Glicosilación , Proteína gp120 de Envoltorio del VIH/metabolismo , Humanos , Macaca mulatta , Neuraminidasa/farmacología , Desnaturalización ProteicaRESUMEN
Anaemia is a common finding in infected individuals, and in many cases is an indicator of disease activity and/or duration. The term 'anaemia of infection' refers to a specific syndrome related to the more broadly defined 'anaemia of chronic disease'. In this syndrome, cytokines produced as part of the host response to infection induce anaemia by well-defined pathophysiological mechanisms. In this chapter, the diagnosis, significance, pathophysiology and treatment of the anaemia of infection will be reviewed. Other mechanisms which can produce anaemia in infected individuals will also be reviewed.
Asunto(s)
Anemia/etiología , Infecciones/complicaciones , Anemia/inducido químicamente , Anemia/diagnóstico , Antiinfecciosos/efectos adversos , Citocinas/efectos adversos , Citocinas/sangre , Citocinas/fisiología , HumanosRESUMEN
An effective vaccine for AIDS may require development of novel vectors capable of eliciting long-lasting immune responses. Here we report the development and use of replication-competent and replication-defective strains of recombinant herpes simplex virus (HSV) that express envelope and Nef antigens of simian immunodeficiency virus (SIV). The HSV recombinants induced antienvelope antibody responses that persisted at relatively stable levels for months after the last administration. Two of seven rhesus monkeys vaccinated with recombinant HSV were solidly protected, and another showed a sustained reduction in viral load following rectal challenge with pathogenic SIVmac239 at 22 weeks following the last vaccine administration. HSV vectors thus show great promise for being able to elicit persistent immune responses and to provide durable protection against AIDS.
Asunto(s)
Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Simplexvirus/inmunología , Vacunas Sintéticas/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Inyecciones Intravenosas , Macaca mulatta , Vacunas contra el SIDAS/biosíntesis , Vacunas contra el SIDAS/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Simplexvirus/genética , Simplexvirus/metabolismo , Vacunas Atenuadas/biosíntesis , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Vacunas Sintéticas/biosíntesis , Vacunas Sintéticas/genética , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Carga Viral , Replicación ViralRESUMEN
BACKGROUND: To determine the concentrations of tumor necrosis factor (TNF) alpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interferon (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES to which hematopoietic progenitors are exposed in vivo in HIV patients and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bone marrow aspirate supernatants from 19 HIV patients undergoing diagnostic evaluation and 14 healthy paid volunteer controls. IL-1 beta and gamma-IFN were rarely detectable. All cytokines/receptors detectable in marrow supernatant, except RANTES, showed mean concentrations 1.6- to 6.2-fold higher in patients with HIV compared to healthy controls. METHODS: Elevated TNF-alpha and MIP-1 beta were associated with marrow involvement by lymphoma, Hodgkin disease, or mycobacterial infection. Concentrations of all cytokines/receptors measured correlated with the severity of anemia. CD8+ lymphocytes were inversely correlated with concentrations of all cytokines measured other than MIP-1 alpha. To identify differences specific to HIV infection, marrow supernatant cytokine concentrations were also evaluated in 9 non-HIV patients undergoing diagnostic marrow examination. Significant differences were observed in TNF alpha, MIP-1 alpha, and IL-1 beta concentrations. RESULTS: These studies demonstrate that concentrations of these cytokines and receptors are elevated in bone marrow supernatant of HIV-infected patients with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients. CONCLUSIONS: Evaluation of local concentrations of cytokines may be relevant to understanding tissue-specific pathology in HIV-infected individuals.
Asunto(s)
Médula Ósea/metabolismo , Citocinas/metabolismo , Infecciones por VIH/metabolismo , Receptores de Citocinas/metabolismo , Adulto , Biomarcadores , Biopsia con Aguja , Médula Ósea/patología , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Alcoholics have increased susceptibility to infections including tuberculosis. Chronic alcohol treatment impairs host response to bovine mycobacterium infection from BCG. This study assesses the role of four cytokines (TNFalpha, IFNgamma, IL-4, and IL-10) in this impaired response. Twenty male C57BL/6 mice were pair-fed on the Lieber DiCarli control (LCD) or ethanol (LED) diets for 28 days. The LED treated subjects ate ad lib and consumed a mean of 13 g/kg/d of ethanol. After 14 days, based on body weight, subjects were randomly divided into four treatment groups of five each. Ten infected with 2x10(6) colony-forming units (CFU) of BCG by tail-vein. On day 28, the mice were sacrificed. Liver was cultured to determine the mycobacteria CFU/g tissue. Spleens were assayed for the levels of TNFalpha, IFNgamma, IL-4, and IL-10 mRNA relative to mRNA levels for a housekeeping gene using a quantitative reverse transcriptase PCR. Without BCG infection, only the mRNA for IFNgamma was increased by LED treatment, 51% (p = 0.0001). BCG infection significantly increased TNFalpha, IFNgamma, and IL-10 mRNA (p<0.0001). IL-4 mRNA decreased (p = 0.0006). Chronic LED plus BCG infection further increased TNFalpha (p = 0.002) and IFN-gamma (p = 0.04); IL-10 was unchanged, whereas IL-4 was marginally further decreased (p = 0.06). CFU/liver increased with LED (mean +/- SD, 72+/-33x10(5) vs. 39+/-17x10(5); p = 0.004). A significant direct correlation was observed between CFU and TNFalpha, r = 0.70, p = 0.03. In conclusion, BCG infection increases TNFalpha, IFNgamma, & IL-10 and decreases IL-4. CFU numbers correlate with mRNA for TNFalpha, and LED inhibits host containment of BCG infection as measured by liver CFU. This study could not identify cytokine alterations in either Th1- or Th2-type immune responses that might contribute to the impaired host response to the BCG infection.
Asunto(s)
Depresores del Sistema Nervioso Central/administración & dosificación , Citocinas/efectos de los fármacos , Etanol/administración & dosificación , Mycobacterium bovis/inmunología , Tuberculosis/inmunología , Animales , Bovinos , Recuento de Colonia Microbiana , Citocinas/inmunología , Interferón gamma/efectos de los fármacos , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Hepatopatías/metabolismo , Hepatopatías/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/efectos de los fármacos , ARN Mensajero/inmunología , Bazo/metabolismo , Tuberculosis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The anemia found in patients with chronic infectious, inflammatory, and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines that mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin-1, and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin, and abnormal mobilization of reticuloendothelial iron stores. In this review, advances in the understanding of the diagnostic, pathophysiologic, and therapeutic aspects of this syndrome are summarized.
Asunto(s)
Anemia/etiología , Citocinas/farmacología , Anemia/fisiopatología , Anemia/terapia , Supervivencia Celular , Enfermedad Crónica , Citocinas/uso terapéutico , Diagnóstico Diferencial , Eritrocitos/fisiología , Eritropoyetina/farmacología , Humanos , Inflamación , SíndromeRESUMEN
Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.
Asunto(s)
Anemia/sangre , Deficiencias de Hierro , Receptores de Transferrina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Biopsia con Aguja , Médula Ósea/metabolismo , Médula Ósea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
In previous studies, we have demonstrated that the inhibitory effects of tumor necrosis factor (TNF) and interleukin (IL)-1 on human erythroid colony formation are indirect and mediated by beta and gamma interferon (IFN), respectively, which act directly upon erythroid colony forming units (CFU-E). The in vitro inhibitory effect of gammaIFN but not betaIFN is reversed by exposure to high concentrations of recombinant human (rh) erythropoietin (EPO). Ceramide, a product of sphingomyelin hydrolysis, is a known mediator of apoptotic effects of TNF, IL-1, and gammaIFN. In this report, the effects of ceramide on CFU-E colony formation and its implication in the model described above are evaluated. Endogenous ceramide produced by exposure to bacterial sphingomyelinase (0.2-2.0 U/mL) and exogenous cell-permeable ceramide (C2-ceramide; 5 and 10 mM) significantly inhibited bone marrow CFU-E colony formation. This effect was reversed by the ceramide antagonist sphingosine-1-phosphate (S-1-P). Inhibition of CFU-E by rhgammaIFN, but not rhbetaIFN, was significantly reversed by S-1-P. rhEPO 10 U/mL reversed CFU-E inhibition by C2-ceramide 10 mM. Exposure of marrow cells to rhgammaIFN led to a 57% increase in ceramide content. The present study demonstrates that colony formation by human CFU-E is inhibited by endogenous and exogenous ceramide, and that inhibition by rhgammaIFN can be reversed by the ceramide antagonist S-1-P. Inhibition of CFU-E colony formation by ceramide and by are both reversed by high concentrations of rhEPO. These findings strongly suggest that ceramide mediates inhibition of human CFU-E colony formation by gammaIFN.