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1.
Nature ; 583(7818): 796-800, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32728237

RESUMEN

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

4.
Rev. clín. esp. (Ed. impr.) ; 217(9): 504-509, dic. 2017. tab
Artículo en Español | IBECS | ID: ibc-169074

RESUMEN

Objetivos. Evaluar el efecto de las dosis altas de corticoides en pacientes ingresados por exacerbación de una enfermedad pulmonar obstructiva crónica (EPOC). Pacientes y métodos. Estudio de cohortes prospectivo de enfermos hospitalizados con EPOC entre enero y marzo de 2015, agrupados en función de la dosis de glucocorticoides recibida (punto de corte: 40mg de prednisona/día). Se compararon los resultados de estancia hospitalaria, y de reingreso y mortalidad a los 3 meses del alta. Resultados. Se analizaron 87 pacientes. La mediana de la dosis diaria recibida fue de 60mg de prednisona/día (rango intercuartílico: 46,67-82,33mg/día); la vía de administración fue endovenosa en el 96,6% de los casos. Se estableció un riesgo relativo (RR) de estancia superior a 8 días de 1,095 [intervalo de confianza (IC) 95%: 0,597-2,007; p=0,765] cuando se usaban dosis de esteroides superiores a 40mg/día. Además, en estos pacientes la hazard ratio (HR) para el reingreso durante los 3 meses siguientes al alta fue de 0,903 [IC 95%: 0,392-2,082; p=0,811] y la mortalidad de 1,832 (IC 95%: 0,229-16,645; p=0,568]. Ni el RR ni las HR observadas variaron de forma estadísticamente significativa tras el ajuste por factores de confusión. Conclusiones. Una dosis superior a 40mg diarios de prednisona en pacientes ingresados por exacerbación de EPOC no se asocia a una menor estancia hospitalaria ni a una disminución del reingreso y de la mortalidad a los 3 meses (AU)


Objectives. To assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). Patients and methods. A prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. Results. We analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. Conclusions. A daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months (AU)


Asunto(s)
Humanos , Corticoesteroides/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Prednisona/administración & dosificación , Recurrencia , Estudios Prospectivos , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Indicadores de Morbimortalidad
5.
Rev Clin Esp (Barc) ; 217(9): 504-509, 2017 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28865758

RESUMEN

OBJECTIVES: To assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: A prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. RESULTS: We analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. CONCLUSIONS: A daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months.

6.
J Hazard Mater ; 166(2-3): 1389-94, 2009 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-19167157

RESUMEN

The heterogeneous reaction of soot with NO can be considered as a means of reduction of the emissions of both pollutants from combustion systems. In this paper, the influence of the presence of CO in the soot-NO reaction is studied. Soot was obtained by pyrolysis at 1373 K of 5000 ppmv acetylene in nitrogen. The study of the influence of CO on the soot-NO reaction was performed in experiments fixing NO concentration at 900 ppmv and introducing different CO concentrations among 0 and 9900 ppmv. An increase in both the carbon consumption rate and NO reduction by acetylene soot was observed as the concentration of CO increases. These results can be explained by the oxide-stripping reaction, CO+C(f)(O)-->CO(2)+C(f). The direct reaction of CO with NO catalyzed by the carbon surface, CO+NO-->CO(2)+1/2N(2) may not be considered in this case the dominant process due to the absence of mineral impurities in the acetylene soot. The influence of CO in the acetylene soot-NO reaction was also tested in the presence of oxygen (250-5000 ppmv). In these conditions and for relatively high CO/O(2) ratios, CO seems to also contribute to NO reduction by the previous oxide-stripping reaction.


Asunto(s)
Acetileno/química , Monóxido de Carbono/química , Óxido Nítrico/química , Hollín/química , Emisiones de Vehículos/prevención & control , Fenómenos Químicos , Oxígeno/química
7.
Gene Ther ; 15(7): 531-6, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18273052

RESUMEN

In utero gene therapy for genetic diseases, such as muscular dystrophies, offers potential advantages over postnatal treatment including vector delivery at the earliest point in the disease and treatment prior to full maturation of the immune system. This study examines in utero gene delivery of full-length murine dystrophin to the murine mdx model for Duchenne muscular dystrophy using a high-capacity adenoviral vector. We examined dystrophin expression, spread of vector, morphology and specific force production of the tibialis anterior muscle 9 weeks after intramuscular in utero injection. Recombinant dystrophin was expressed in the hindlimb muscles, with the majority of animals having expression in two muscles of the injected hindlimb. The dystrophin-glycoprotein complex was restored in those muscle fibers expressing recombinant dystrophin. Analysis of the percentage of dystrophin-expressing muscle fibers with centrally placed nuclei revealed effective protection from cycles of degeneration and regeneration normally seen in muscle fibers lacking dystrophin. However, due to low levels of muscle gene transfer, further advances in the efficiency of adenoviral vector-mediated gene delivery would be required for clinical applications of in utero gene therapy for primary myopathies such as Duchenne muscular dystrophy.


Asunto(s)
Distrofina/genética , Terapias Fetales/métodos , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Distrofia Muscular de Duchenne/terapia , Adenoviridae/genética , Animales , Animales Recién Nacidos , Distrofina/análisis , Distrofina/metabolismo , Femenino , Expresión Génica , Vectores Genéticos/genética , Miembro Posterior , Inyecciones Intramusculares , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Distrofia Muscular Animal , Distrofia Muscular de Duchenne/embriología , Distrofia Muscular de Duchenne/patología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción Genética/métodos
8.
Biofarbo ; 15(15): 51-54, dic. 2007. tab
Artículo en Español | LILACS | ID: lil-507160

RESUMEN

La infección por helicobacter pylori está distribuida a nivel mundial, la prevalencia es del 50%. Esta infección está asociada a enfermedades como las gastritis, úlceras, cancer gástrico y linfoma de MALT. El objetivo es describir la relación existente entre enfermedad e infección por helicobacter pylori.


Asunto(s)
Humanos , Gastritis/prevención & control , Helicobacter pylori/patogenicidad
9.
Biofarbo ; 15(15): 37-42, dic. 2007. tab
Artículo en Español | LILACS | ID: lil-507162

RESUMEN

Helicobacter pylori es una bacteria asociada a patologías gástricas como gastritis, ulceras, cancer y linfoma de MALT. De acuerdo a estudios realizados en la ciudad de La Paz-Bolivia aproximadamente el 50% de la población esta infectada por esta bacteria.


Asunto(s)
Gastritis/diagnóstico , Helicobacter pylori/patogenicidad
10.
Gene Ther ; 12(1): 39-47, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15483668

RESUMEN

In utero gene delivery could offer the advantage of treatment at an early stage for genetic disorders such as Duchenne muscular dystrophy (DMD) in which the inevitable process of muscle degeneration is already initiated at birth. Furthermore, treatment of fetal muscle with adenoviral (Ad) vectors is attractive because of a high density of Ad receptors, easy vector accessibility due to immaturity of the basal lamina and the possibility of treating stem cells. Previously, we demonstrated the efficient transduction of fetal muscle by high-capacity Ad (HC-Ad) vectors. In this study, we compared HC-Ad and first-generation Ad (FG-Ad) vectors for longevity of lacZ transgene expression, toxicity and induction of immunity after direct vector-mediated in utero gene delivery to fetal C57BL/6 mice muscle 16 days after conception (E-16). The total amount of beta-galactosidase (betagal) expressed from the HC-Ad vector remained stable for the 5 months of the study, although the concentration of betagal decreased due to muscle growth. Higher survival rates that reflect lower levels of toxicity were observed in those mice transduced with an HC-Ad vector as compared to an FG-Ad vector. The toxicity induced by FG-Ad vector gene delivery was dependent on mouse strain and vector dose. Animals treated with either HC-Ad and FG-Ad vectors developed non-neutralizing antibodies against Ad capsid and antibodies against betagal, but these antibodies did not cause loss of vector genomes from transduced muscle. In a mouse model of DMD, dystrophin gene transfer to muscle in utero using an HC-Ad vector restored the dystrophin-associated glycoproteins. Our results demonstrate that long-term transgene expression can be achieved by HC-Ad vector-mediated gene delivery to fetal muscle, although strategies of vector integration may need to be considered to accommodate muscle growth.


Asunto(s)
Adenoviridae/genética , Enfermedades Fetales/terapia , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Músculo Esquelético/embriología , Distrofia Muscular de Duchenne/terapia , Animales , Distrofina/genética , Expresión Génica , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/metabolismo , Transgenes
11.
Br J Dermatol ; 150(6): 1186-9, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15214908

RESUMEN

BACKGROUND: In 1989 we demonstrated that 71% of children referred to our paediatric dermatology clinic with atopic dermatitis (AD) had been subject to dietary manipulation by their parents in order to manage their disease. We have re-examined our clinic population to determine whether the documented rise in the use of complementary therapy in children with skin disease has been accompanied by a rise in dietary manipulation. OBJECTIVES: To qualify and quantify the usage of dietary manipulation in children with AD in secondary care. METHODS: A face-to-face structured questionnaire study of 100 children with AD. RESULTS: The mean age of the children interviewed was 7.3 years (median 5.9, range 0.6-17.1) and ethnic origin was 59% white, 35% Indo-Asian, 3% Afro-Caribbean and 3% mixed race. Seventy-five per cent of patients (75 of 100) had tried some form of dietary exclusion; the most common foods omitted were dairy products in 48% (36 of 75), eggs in 27% (20 of 75) and cow's milk in 25% (19 of 75). Forty-one per cent of patients (41 of 100) had tried some form of dietary supplementation. The most common dietary supplement was evening primrose oil in 59% (24 of 41), of whom 13% (three of 24) felt this had helped their skin. Only 51% (38 of 75) had consulted a doctor or dietician before commencing any dietary change, but 39% (29 of 75) felt that their skin had improved as a result of this dietary manipulation. CONCLUSIONS: In comparison with our previous study, the proportion of patients excluding foods from their diet had increased from 71% to 75%. The proportion of these dietary changes that are unsupervised has remained the same, as have the food types avoided. The proportion of patients who report that unsupervised dietary manipulation is beneficial has increased from 10% to 39%.


Asunto(s)
Dermatitis Atópica/dietoterapia , Dieta , Padres , Autocuidado , Adolescente , Animales , Niño , Preescolar , Productos Lácteos , Dermatitis Atópica/etiología , Suplementos Dietéticos , Huevos , Ácidos Grasos Esenciales/administración & dosificación , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Humanos , Lactante , Ácidos Linoleicos , Masculino , Leche , Oenothera biennis , Aceites de Plantas , Ácido gammalinolénico
12.
Gene Ther ; 10(21): 1821-9, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12960972

RESUMEN

High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle.


Asunto(s)
Adenoviridae/genética , Enfermedades Fetales/terapia , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Músculo Esquelético/embriología , Oligopéptidos/genética , Secuencias de Aminoácidos , Animales , Femenino , Expresión Génica , Marcación de Gen , Integrinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Embarazo , Transducción Genética/métodos , beta-Galactosidasa/genética
13.
Br J Dermatol ; 149(3): 566-71, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14510990

RESUMEN

BACKGROUND: The use of 'complementary' or 'alternative' medicine continues to rise in patients with skin disease, especially in those with chronic, inflammatory dermatoses. OBJECTIVES: To qualify and quantify the usage of complementary medicine (CM) in children with atopic dermatitis (AD) in secondary care. METHODS: A face-to-face structured questionnaire study of 100 consecutive children with AD and their parent or guardian. RESULTS: The mean age of the children interviewed was 7.3 years (median age 6.0 years, range 0.6-17.1) and ethnic origin was 59% white, 35% Indian, 3% Afro-Caribbean and 3% mixed race. Forty-six of 100 patients (46%) had used, or were currently using, CM. Of the 54 patients who had not yet used CM, 17 of 54 (31%) said they intended to try this in the future. The most commonly used CM was Chinese herbal medicine by 20 of 46 patients (43% of those who had used CM), followed by herbal medicine (41%) and homeopathy (35%). Of 74 patients using CM, 26 (35%) felt their AD had improved while 39 of 74 (53%) reported that it had remained unchanged. Twenty-six of 46 (56%) CM users in this study would not recommend CM to other patients with AD. There was a strong association between the use of CM and ethnicity (P = 0.01). Half of the patients who had used CM (23 of 46) had used it on the recommendation of family or friends with skin disease, 17 of 46 (37%) from family or friends without skin disease and three of 46 (6%) each from health professionals or from the media or internet. Twenty-five of 46 (54%) of CM users did so because conventional treatment was not working, and eight of 46 (17%) because they were worried about the side-effects of conventional treatment. While 39 of 100 (39%) of all patients felt that CM was safer than conventional medicine, only 14 of 100 felt it was more efficacious. Fifty-one of 100 were happy to combine both types of treatment and 66 of 100 felt that CM should be available from the National Health Service. CONCLUSIONS: In a population of children with AD attending a teaching hospital clinic in Leicester, U.K., 63% use or intend to use CM. This use is associated with ethnicity.


Asunto(s)
Terapias Complementarias/estadística & datos numéricos , Dermatitis Atópica/terapia , Hospitalización/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Inglaterra , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Satisfacción del Paciente , Encuestas y Cuestionarios
14.
Rev. méd. Chile ; 130(10): 1101-1112, oct. 2002. tab
Artículo en Español | LILACS | ID: lil-339172

RESUMEN

Background: Most individual and organizational costs related to job stress are due to preventable health problems. To study the impact of occupational stress in Chile, an instrument that evaluates the different variables involved in the stress process is required. Aim: To study the effects of work stressors and psychological variables on health among Chileans managers. To study reliability and validity of the Spanish version of the Occupational Stress Indicator (OSI-2). Subjects and methods: A translated version of the OSI-2 was applied to a sample of 264 white-collar managers. Results: A high frequency of symptoms was reported by our sample. Back pain was the most frequently reported symptom in managers with high levels of stress. Regression analysis showed that, together, work stressors and psychological characteristics significantly explained self-perceived mental (27,6 percent) and physical (22,9 percent) health variance. Responsibilities of the executive role were the stressors most highly associated with poor stress outcomes. The psychological variables most strongly correlated with mental and physical health were Problem-focused Coping and the subscale Impatience of Type A Behavior. The reliability and validity of the OSI-2, Spanish version, were reasonably high. Conclusions: The transactional model of work stress was confirmed in a sample of Chilean managers evaluated with the Spanish version of the OSI-2


Asunto(s)
Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Enfermedades Profesionales , Estrés Psicológico/epidemiología , Riesgos Laborales , Carga de Trabajo , Distribución por Sexo , Predicción/métodos , Pruebas Psicológicas
16.
Mol Ther ; 3(5 Pt 1): 665-72, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11356071

RESUMEN

We previously reported that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. This zone of higher infection is dependent on the alpha(v)beta(3) integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissues surrounding liver metastases. When a recombinant adenovirus encoding interleukin-12 (AdCMVIL-12) is given into a subcutaneous tumor nodule in mice also bearing concomitant liver tumors, a fraction of AdCMVIL-12 reaches the systemic circulation and infects liver tissue, especially at the malignant/healthy tissue interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy.


Asunto(s)
Adenoviridae/genética , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Interleucina-12/genética , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Receptores de Vitronectina/metabolismo , Linfocitos T/metabolismo , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Animales , Anticuerpos Monoclonales/metabolismo , Adhesión Celular , Movimiento Celular , Separación Celular , Endotelio/metabolismo , Femenino , Citometría de Flujo , Galactósidos/metabolismo , Inmunohistoquímica , Indoles/metabolismo , Linfocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Metástasis de la Neoplasia , Linfocitos T Citotóxicos/metabolismo , Transgenes
17.
Hepatology ; 33(1): 52-61, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11124820

RESUMEN

The use of gene therapy to enhance antitumor immunity has emerged as a promising procedure to fight cancer. In this study we have tested the ability of an adenovirus carrying interleukin 12 (IL-12) gene (AdCMVIL-12) to eliminate tumoral lesions in 3 animal models of orthotopic hepatocellular carcinoma (HCC). Intratumoral injection of AdCMVIL-12 in animals with a single big tumor nodule implanted in the liver resulted in significant inhibition of tumor growth in a dose-dependent manner. Fifty percent of animals that received a dose of 5 x 10(9) plaque-forming units, showed complete regression of the tumor 2 weeks after treatment. In animals with 2 independent tumor nodules in the left liver lobe, injection in only one of them of 5 x 10(9) pfu AdCMVIL-12 induced, 15 days after therapy, complete regression of 50% of treated tumors and also of 50% of untreated lesions, with 60% long-term survival. Rats that were tumor free after therapy with AdCMVIL-12 showed protection against tumor rechallenge. A group of rats received the carcinogen diethylnitrosamine and developed multiple hepatic dysplasic nodules of 1 to 5 mm in diameter. These animals were treated by intrahepatic artery injection of either AdCMVIL-12 (5 x 10(9) pfu) or control vector. In this model AdCMVIL-12 induced complete tumor regression in 20% of treated rats and inhibited tumor growth in 60% of cases with an increase in rat survival. Activation of natural killer (NK) cells and inhibition of angiogenesis were found to be antitumor mechanisms set in motion by AdCMVIL-12. Our data indicate that experimental HCC can be efficiently treated by intratumoral or intravascular injection of adenovirus expressing IL-12.


Asunto(s)
Adenoviridae/genética , Carcinoma Hepatocelular/terapia , Terapia Genética , Interleucina-12/genética , Neoplasias Hepáticas/terapia , Animales , Carcinógenos , Carcinoma Hepatocelular/inducido químicamente , Línea Celular , Dietilnitrosamina , Inyecciones Intralesiones , Células Asesinas Naturales/fisiología , Neoplasias Hepáticas/inducido químicamente , Masculino , Neoplasias Primarias Múltiples/terapia , Neovascularización Patológica/prevención & control , Ratas , Ratas Endogámicas BUF , Ratas Wistar
18.
Gene Ther ; 7(21): 1824-32, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11110414

RESUMEN

We have evaluated gene transfer efficiency to tumor nodules in diethylnitrosoamine (DENA)-induced hepatocellular carcinoma (HCC) in rats using adenoviral vectors administered by three different routes: intraportal, intra-arterial and intratumoral injection. Our results showed that intraportal infusion could not transduce tumor nodules greater than 1 mm in diameter while the intra-arterial route allowed transduction of nodules up to 2-5 mm in diameter. Tumors greater than this size were resistant to transduction by intravascular route, but could be transduced by direct intratumoral injection, indicating that the obstacle preventing gene transfer to tumor cells was mainly at the level of tumor vasculature and not at the level of neoplastic cells. We have studied the extracellular matrix in tumoral lesions to assess whether nodules with different size and histological pattern have different profiles in relation to transduction efficacy. Immunohistochemical detection showed a high expression of fibronectin (FN), laminin (LN) and alpha-smooth muscle actin (alpha-SMA) in those large HCC, which were resistant to adenoviral infection. Intra-arterial infusion of vasoactive compounds (histamine, angiotensin II or nitric oxide donor nitroglycerin) before vector administration enhanced gene transfer to tumor nodules that were poorly transduced without pre-treatment. Nitroglycerin was active to enhance transduction of large tumors with trabecular or pseudoglandular histological pattern, which were impermeable to adenoviral vectors even after histamine or angiotensin treatments. Our data indicate the presence of a physical barrier between blood and neoplastic cells, which prevents transduction of the tumor by vectors given by the intravascular route. The thickness and impermeability of the barrier increases as the tumor nodule grows. Vasoactive compounds may be of value in gene therapy of liver cancer by increasing transduction efficiency by intravascularly administered vectors.


Asunto(s)
Terapia Genética/métodos , Neoplasias Hepáticas Experimentales/terapia , Transfección/métodos , Vasodilatadores/uso terapéutico , Actinas/análisis , Adenoviridae/genética , Angiotensina II/uso terapéutico , Animales , Dietilnitrosamina , Matriz Extracelular/química , Fibronectinas/análisis , Expresión Génica , Vectores Genéticos/administración & dosificación , Inmunohistoquímica , Inyecciones Intraarteriales , Operón Lac , Laminina/análisis , Neoplasias Hepáticas Experimentales/patología , Microesferas , Nitroglicerina/uso terapéutico , Sistema Porta , Ratas , Ratas Wistar , Almidón/uso terapéutico
19.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 27(9): 324-328, nov. 2000. tab
Artículo en Es | IBECS | ID: ibc-20960

RESUMEN

Debido a la gran importancia mundial del cáncer de cuello uterino, se analizan los posibles factores de riesgo que pueden estar relacionados con esta neoplasia. Se procesan muestras de 382 mujeres supuestamente sanas y 226 muestras de mujeres diagnosticadas de neoplasia intracervical, realizando una detección de ADN-PVH en endocérvix, así como una encuesta epidemiológica de posibles factores de riesgo (FR) asociados al carcinoma. El procesamiento estadístico se realiza con los programas EpiInfo 6 y SPSS mediante la prueba de la X2 en el análisis bivariante y regresión logística múltiple (RLM) en el multivariante. En el análisis bivariante se encuentra asociación estadísticamente significativa entre neoplasia cervical y 19 de los FR analizados, mientras que en el análisis multivariante encontramos que el modelo de RLM más adecuado contiene sólo tres variables, uso de anticonceptivos orales, presencia de PVH de alto riesgo y tabaco. Al igual que en otros estudios epidemiológicos, la asociación entre el carcinoma cervical y la presencia de PVH en endocérvix es clara, así como el tabaco, que en nuestro modelo de RLM duplica el efecto del anterior FR. La ecuación predice que el efecto de PVH es el más importante (odds ratio [OR] = 40) y además se potencia con el tabaquismo y con el uso de anticonceptivos orales (OR de las tres variables = 241) (AU)


Asunto(s)
Adulto , Femenino , Humanos , Factores de Riesgo , 31574/cirugía , 31574/complicaciones , 31574/diagnóstico , Conización/métodos , Histerectomía/métodos , Análisis Multivariante , Estudios de Casos y Controles , 31574/epidemiología , 31574/etiología , 31574/fisiopatología
20.
Enferm Infecc Microbiol Clin ; 18(3): 120-4, 2000 Mar.
Artículo en Español | MEDLINE | ID: mdl-10905013

RESUMEN

INTRODUCTION: The increasing incidence of Candida yeasts infections and its hospital and community repercussion (vaginal thrush), as well as the will to acquire the knowledge of the new antifungal that were launched to the therapeutic store, have motivated us to identify that type of yeasts from different sources, as well as to study their behaviour against the antifungal, using commercial procedures with easy clinical application. MATERIALS AND METHODS: An amount of 317 Candida yeasts were identified through commercial procedures (CHROMagar Candida and Auxacolor): 108 vaginals, 138 from ICU newborn children and 71 from ICU adults, while the antifungal drug susceptibilities was done to 199 of the isolated ones using another commercial procedure (Fungitest). RESULTS AND CONCLUSIONS: Candida albicans is identified as the most frequent in both hospital and community samples (78.7 and 45.93%, respectively), followed by Candida glabrata (19.44 and 28.23%, respectively). The sensitivity to amphotericin B and to 5-flucytosine was very high in every studied group, while sensitivity to imidazole derivatives depends on the samples source (lower sensitivity in the ICU newborn isolated ones) and the species (C. glabrata is less sensitive than C. albicans).


Asunto(s)
Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Adulto , Candidiasis Bucal/tratamiento farmacológico , Candidiasis Bucal/microbiología , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/microbiología , Farmacorresistencia Microbiana , Femenino , Humanos , Recién Nacido , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana
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