Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease that may undergo periods of activity followed by remission. We aimed to identify the endogenous regulatory mechanisms that may promote disease remission. Transcriptional and protein analysis of the intestinal mucosa revealed that the IL-1 decoy receptor, interleukin-1 receptor type 2 (IL1R2), was upregulated in remission compared with active UC and controls. We identified epithelial cells as being responsible for increased IL-1R2 production during remission. Expression of IL1R2 was negatively regulated by Wnt/beta-catenin signals in colonic crypts or epithelial stem cell cultures; accordingly, epithelial stem cells upregulated IL-1R2 upon differentiation. Blocking IL-1R2 in isolated colonic crypt cultures of UC patients in remission and T-cell cultures stimulated with biopsy supernatant from UC patients in remission boosted IL-1ß-dependent production of inflammation-related cytokines. Finally, IL1R2 transcription was significantly lower in patients that relapsed during a 1-year follow-up period compared with those in endoscopic remission. Collectively, our results reveal that the IL-1/IL-1R2 axis is differentially regulated in the remitting intestinal mucosa of UC patients. We hypothesize that IL-1R2 in the presence of low concentrations of IL-1ß may act locally as a regulator of intestinal homeostasis.

TGF-beta in CAF-mediated tumor growth and metastasis.

TGF-beta signaling is one of the major pathways controlling cell and tissue behavior not only in homeostasis but also in disease. During tumorigenesis TGF-beta orchestrated processes are key due to its dual role as tumor suppressor and tumor promoter. Important functions of this pathway have been described in a context-dependent manner both in epithelial cancer cells and in the tumor microenvironment during tumor progression. Carcinoma-associated fibroblasts (CAFs) are one of the most abundant stromal cell types in virtually all solid tumors. CAFs favor malignant progression by providing cancer cells with proliferative, migratory, survival and invasive capacities. A complex network of signaling pathways underlying their tumor-promoting properties is beginning to take shape. In this review, we examine current evidence on the emerging mechanisms involving TGF-beta in CAF-mediated cancer progression, and discuss their potential as therapeutic targets.

Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis.

Epidermal keratinocytes and hair follicle (HF) stem cells (SCs) expressing oncogenes are competent at developing squamous cell carcinomas (SCCs) in epidermis and HFs, respectively. To determine whether bulge and hair germ (HG) SCs from HF contribute to SCC generation at distant epidermis, the most frequent epidermal region where these lesions arise in human skin, we used a skin cancer mouse model expressing E6 and E7 oncoproteins from Human papillomavirus (HPV) 16 in SCs and basal keratinocytes. This previously described mouse model recapitulates the human skin papillomavirus-induced SCC pathology. We show that E6 and E7 expression promote the expansion of keratin 15 (K15)-expressing cells. These K15(+) aberrant cells exhibit some HGSC markers and diminished expression of Tcf3 and Sox9 hair SC specification genes, which are accumulated in HFs and mislocalized to interfollicular epidermis. Leucine-rich G-protein-coupled receptor 5 (Lgr5)-expressing SCs, localized in the bulge and HG, are the origin of the expanded K15(+) cell population. A large subset of the Lgr5(+) SC progeny, expressing K15 and P-cadherin, is aberrantly mobilized to the upper region of HFs and the epidermis, and accumulates at E6/E7-induced pre-neoplastic lesions and epidermal tumors. These findings indicate that aberrant accumulation of altered SCs in HFs and their subsequent migration to the epidermis contribute to HPV-induced tumor development.

Fibromyalgia in patients with ankylosing spondylitis: prevalence and utility of the measures of activity, function and radiological damage.

OBJECTIVES: To determine the prevalence of fibromyalgia (FM) in ankylosing spondylitis (AS). To evaluate the effect of FM on the measures of activity in AS. To analyse predictive factors in order to identify this group of patients. PATIENTS AND METHODS: A cross-sectional study based on 462 patients with definite ankylosing spondylitis included in the REGISPONSER. Sociodemographic data, clinical features, Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS radiology index (BASRI), Stoke modified index (Sasss-m), laboratory data, Short-Format 12 (SF-12), AS specific quality of life (ASQoL), Fibromyalgia Impact Questionnaire (FIQ) and treatments used were all documented. To diagnose FM, the ACR 1990 criteria had to be fulfilled. All statistical tests were performed using STATA. RESULTS: The prevalence of fibromyalgia in all AS was 4.11%. Among the women with AS, the prevalence of FM increased to 10.83%. The BASDAI, BASFI and total BASRI were strongly influenced by the presence of FM. The inverse relationship between BASDAI or BASFI and total BASRI was taken to generate a ratio. Accordingly, if the patient presented BASDAI/BASRI ≥1.5 or BASFI/BASRI ≥1.08, the probability of having FM was very high. CONCLUSIONS: There is an increased risk of FM in females with AS. The fact of having FM distorts the measures of activity and functional damage of AS. As a result, it is possible that some patients with AS and FM are being overtreated. The BASDAI/BASRI and BASFI/BASRI ratios are very useful to identify these patients.

Relationship between spinal mobility and disease activity, function, quality of life and radiology. A cross-sectional Spanish registry of spondyloarthropathies (REGISPONSER).

OBJECTIVE: To determine the relationship between anthropometric measurements and disease activity, functional capacity, quality of life and radiology in Spanish patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study was made of 842 patients with definite ankylosing spondylitis (REGISPONSER). Sociodemographic data, spinal mobility measurements, Bath AS disease activity index (BASDAI), nocturnal pain, Bath AS radiology index (BASRI), Bath AS functional index (BASFI), the Short-Format 12 (SF-12) and the AS specific quality of life (ASQoL) questionnaire were applied. Pearson correlation coefficient analysis and regression models were constructed. RESULTS: There was moderate correlation between fingertip-to-floor distance and lateral cervical rotation with the BASFI (p<0.01). Good correlation was evident between wall-occiput distance and lateral cervical rotation with the BASRI (p<0.01). Moderate correlation was found between chest expansion, the Schober modified test and fingertip-to-floor distance with the total BASRI (p<0.01). The anthropometric measurement with the lowest correlation value was lateral lumbar flexion. Significant association was found between the Schober modified test and BASFI, BASDAI and BASRI (R(2) = 0.37; p<0.001); chest expansion and BASFI, BASDAI and BASRI (R(2) = 0.25; p<0.001); wall-occiput distance and BASFI, BASRI and ASQoL (R(2) = 0.44; p<0.001); fingertip-to-floor distance and BASFI and BASRI (R(2) = 0.30; p<0.001); and lateral cervical rotation and BASFI and BASRI (R(2) = 0.34; p<0.001). CONCLUSION: In our study, wall-occiput distance and lateral cervical rotation showed the strongest correlation to BASRI. Similarly, fingertip-to-floor distance and lateral cervical rotation exhibited the closest correlation to BASFI.

La detección precoz auditiva de los neonatos / Newborn hearing screening

Internacionalmente está totalmente asumida lanecesidad de la detección precoz auditiva de formauniversal en los neonatos, existiendo protocolos ytecnologías para llevarla a cabo. Se han suscitadocontroversias sobre la sensibilidad, la especificidad ylas técnicas de realización de las mismas.Las metas ideales a alcanzar son: detección precozantes del mes, establecimiento del diagnóstico a los3 meses e inicio de rehabilitación protésica y logopédicaa los 6 meses. Una rehabilitación precoz supone laposibilidad de utilizar plenamente los períodos críticosde aprendizaje y conseguir la maduración de la víaauditiva de forma correcta, obteniéndose una calidadde lenguaje próxima al normooyente.El congreso bianual Newborn Hearing Screening2008 (NHS, 2008) ha supuesto la posibilidad de contrastarnuestros criterios en un foro en el que se hanpresentado más de 60 programas de detección precozauditiva de 30 países distintos.Se incluyen en las conclusiones algunos de los puntosrecogidos en el resumen final de este importantecongreso después del seguimiento de las distintasconferencias sobre la neuropatía y el screening auditivouniversal

It is all over recognized the need of the universal newborn hearing screening, even there are several protocols to perform it. There are some differences about the specificity, sensibility and technical ways to make the tests.The ideal is: detection before one month, diagnosis inthree months and to begin the prothesis and logopedicrehabilitation at six months. An early rehabilitationgives the possibility to use properly the critical periodand to develop the maturation of the nervous hearingsystem, obtaining a quality of language near the normalone.The NHS (Newborn Hearing Screening) 2008 biannualcongress has been a good opportunity to contrast ourcriteria. 60 newborn screening programes have beenpresented from 30 different countries.We present a summary of several aspects mentioned inthe final conclusions of this important congress afterattending thel presentations about neurophathy and universal newborn hearing screening programmes (AU)

Disease pattern of spondyloarthropathies in Spain: description of the first national registry (REGISPONSER) extended report.

OBJECTIVE: The national registry of spondyloarthropathies (REGISPONSER) is launched to classify patients with this group of diseases treated in Spanish rheumatology clinics. This manuscript describes the methodological and organizational background as well as characteristics of patients finally included, and provides a comparative analysis between characteristics of both ankylosing spondylitis and undifferentiated spondyloarthropathy groups of patients. PATIENTS AND METHODS: Twelve members of the GRESSER group have participated in the registry, for a one-year recruitment period. All consecutively registered adult patients treated in their clinics met the classification criteria of the European Spondyloarthropathies Study Group (ESSG). Data collected reflect the socio-demographic characteristics, as well as disease activity and functional status, clinical form at onset, treatment used and quality of life; all measured by standard instruments. RESULTS: Throughout 1 yr, 1385 patients have been included in the registry: 939 males (68%) and 440 females (32%), with an average age of 47 +/- 13 years (mean +/- s.d.), and an average disease duration of 12 +/- 9 years. Diagnoses of the included patients were: AS (n = 842, 61%), PsA (n = 290, 21%), u-SpA (n = 205, 15%), reactive arthritis (n = 16, 1.2%), inflammatory bowel disease arthritis (n = 13, 0.9%) and JCA-spondyloathropathy (n = 13, 0.9%). Regarding clinical form, 54% had axial disease, 20% peripheral disease, 24% mixed disease and 0.6% isolated enthesitic form. Low-back pain was the first symptom reported in 53% of the patients, and most common extra-articular disease manifestations were psoriasis (25%), anterior uveitis (16%) and intestinal inflammatory disease (4%). Some kind of work disability was reported by 353 patients (25.5%). CONCLUSIONS: Such databases are very useful to obtain information about characteristics of SpA patients treated in a certain location or following a specific treatment practice, and provide a tool for assessing the impact of the disease. Data collected in this registry provide an appropriate clinical and demographic profile of patients suffering from SpA in Spain.

Respuesta del panel de expertos / Experts board's reply

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Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer's disease over a 6-month period.

There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p > 0.05). Treatment with AChEIs significantly delays the global cognitive impairment associated with AD for at least 6 months. Our study found no significant differences in efficacy between donepezil, galantamine and rivastigmine. Further studies in the context of daily clinical practice will determine the clinical significance of the changes observed. An important variability of the response to the treatment was observed in treated patients.

Aplicaciones clínicas de la determinación plasmática del péptido natriurético auricular / Clinical applications of auricular natriuretic peptide plasma level quantification

El péptido natriurético auricular tipo B (BNP) es una neurohormona sintetizada en los ventrículos. En el momento actual, la medida del BNP se puede realizar mediante una rápida prueba que está disponible tanto en el ámbito ambulatorio como en el hospitalario. Se ha probado su utilidad en el Servicio de Urgencias para el diagnóstico de la insuficiencia cardíaca congestiva en pacientes con causa no clara de disnea. Se ha estudiado la utilidad de la determinación del nivel de BNP como criterio de ingreso hospitalario, así como en la toma de decisiones respecto a la adecuación del tratamiento durante la hospitalización y el momento del alta. En pacientes ambulatorios, usar el BNP como guía para intensificar la terapéutica farmacológica muestra un prometedor futuro en la disminución de la tasa de eventos adversos asociados con este diagnóstico. La medida del BNP parece también proporcionar información pronóstica en pacientes con insuficiencia cardíaca, así como ser útil en la detección de la disfunción ventricular izquierda asintomática. Además, se intuye su utilidad en otros campos como en el síndrome coronario agudo y el corazón trasplantado, sin olvidar el uso reciente del BNP recombinante humano, nesiritide, en el tratamiento de la insuficiencia cardíaca descompensada (AU)

Neuropsychological profile of Alzheimer's disease in women: moderate and moderately severe cognitive decline.

INTRODUCTION: Alzheimer's disease (AD) is characterised by progressive cognitive and functional decline. There is evidence that AD is more prevalent in women. This study aims at identifying the clinical and sociodemographic variables associated with the cognitive functions and the pattern of decline in women with moderate to moderately severe AD. METHODS: Cross-sectional observational study of 165 women with dementia of the AD type according to NINCDS-ADRDA criteria. The cognitive functions were assessed using the Cambridge Cognitive Examination (CAMCOG). The sociodemographic and clinical data were collected from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) interview, and the Neuropsychiatric Inventory (NPI) was administrated to the caregiver. RESULTS: The number of years of schooling and the score on the CAMDEX depression scale were the variables associated with the CAMCOG score. The effect of these variables was not homogenous for all the CAMCOG subtests. CONCLUSIONS: The number of years of schooling and the presence of depressive symptomatology influence the results of the neuropsychological exploration, but the effect is moderate and not homogenous for all the CAMCOG subtests. The differences in cognitive profile between moderate and moderately severe are characterised by a greater effect on temporal orientation, calculation and perception.

Incidencia clínica de la demencia por cuerpos de Lewy / Clinical incidence of dementia with Lewy bodies

Introducción y objetivos. El reconocimiento de la demencia por cuerpos de Lewy (DCL) como una entidad neurodegenerativa independiente es relativamente reciente. Aún se han realizado pocos estudios epidemiológicos de prevalencia que incluyan la DCL y no existen estudios de incidencia. El objetivo del presente trabajo es de terminar la incidencia clínica anual de la DCL. Pacientes y métodos. Estudio retrospectivo observacional del diagnóstico de todos los sujetos que acudieron a la UVAMID entre los años 1999 y 2001. La valoración clínica se realizó de modo estandarizado según el protocolo de la UVAMID, que incluye la historia clínica realizada a través de una entrevista al paciente y a un informador fiable, un examen médico general y neurológico, una exploración neuropsicológica y un conjunto de pruebas complementarias. Resultados. La incidencia en la práctica clínica de la DCL fue de 26/100.000 casos anuales. Por grupos de edad, se observó un aumento progresivo de la incidencia hasta el intervalo de 80-84 años y el 63 por ciento de los casos de DCL fueron hombres. Conclusiones. Los resultados del presente estudio señalan que los casos de DCL representaron el 2 por ciento del total de casos nuevos anuales. La principal limitación del presente trabajo es que los pacientes, al remitirse a consulta desde los centros de atención primaria, forman una muestra no representativa, clínicamente sesgada, que limita la extrapolación de los resultados (AU)

Introduction and aims. Dementia with Lewy bodies (DLB) has only relatively recently been acknowledged as an independent neurodegenerative entity. Until now few epidemiological prevalence studies have been carried out that include DLB and there are no studies about its incidence. The aim of this study is to determine the annual clinical incidence of DLB. Patients and methods. We performed an observational retrospective study of the diagnosis of all the individuals who were attended at the UVAMID (Memory and Dementia Assessment Unit) between 1999 and 2001. The clinical assessment was performed in a standardised manner following the UVAMID protocol, which includes the medical history, obtained by interviewing the patient and a reliable informant, a general medical and neurological check-up, neuropsychological exploration and a set of complementary tests. Results. The incidence of DLB in clinical practice was found to be 26/100,000 cases per year. By age groups, a progressive increase in incidence was seen until the 80-84 year old bracket and 63% of the cases of DLB were males. Conclusions. The results of this study show that cases of DLB made up 2% of the total number of new annual cases. The main limitation of this study lies in the fact that, because patients were referred to clinic from primary health care centres, they do not constitute a representative sample that is clinically unbiased, and this imposes restraints on the extrapolation of results (AU)

[Tolerance and adverse events of treatment with acetylcholinesterase inhibitors in a clinical sample of patients with very slight and mild Alzheimer s disease over a six-month period]. / Tolerancia y acontecimientos adversos del tratamiento con inhibidores de la acetilcolinesterasa en una muestra clínica de pacientes con enfermedad de Alzheimer de gravedad mínima y leve durante un período de seis meses.

INTRODUCTION: At present acetylcholinesterase inhibitors (AChEI) are used in the treatment of the cognitive deterioration associated with Alzheimer s disease (AD). The side effects of these drugs are linked with the increase in acetylcholine, which limits their effectiveness, and must be adjusted to the patient close to the maximum tolerated dose. PATIENTS AND METHODS: We conducted a comparative retrospective study of the tolerance and the adverse events (AE) of two AChEI in a group of patients with very slight and mild probable AD over a 6 month period. RESULTS: The sample was made up of 175 patients, of which 134 began therapy with 5 10 mg/day of donepezil and 41 with 6 12 mg/day of rivastigmine. 20% of the patients presented AE and 8% abandoned the treatment. Gastrointestinal disorders (GID) were the main AE observed (57.1%). Only 6% of the patients treated with donepezil abandoned the therapy because of the AE as opposed to 14.6% of the patients treated with rivastigmine. Patients treated with rivastigmine displayed a higher incidence of GID and the relative risk of presenting GID was 4.4 times higher than in the patients treated with donepezil. CONCLUSIONS: The GID associated to therapy with AChEI are the main reason for abandoning treatment and occur more frequently in patients treated with rivastigmine.

Tolerancia y acontecimientos adversos del tratamiento con inhibidores de la acetilcolinesterasa en una muestra clínica de pacientes con enfermedad de Alzheimer de gravedad mínima y leve durante un período de seis meses / Tolerance and adverse events of treatment with acetylcholinesterase inhibitors in a clinical sample of patients with very slight and mild alzheimer's disease over a six-month period

Introducción. Actualmente, en el tratamiento del deterioro cognitivo asociado a la enfermedad de Alzheimer (EA) se utilizan los inhibidores de la acetilcolinesterasa (iACh). Los efectos secundariosde estos fármacos se asocian al aumento de acetilcolina, lo que limita su efectividad, y se debe ajustar al paciente hasta la dosis máxima tolerada . Pacientes y métodos. Se realiza un estudio comparativoretrospectivo de la tolerancia y de los acontecimientos adversos (AA) de dos iACh en un grupo de pacientes con EA probable de gravedad mínima y leve durante un período de 6 meses. Resultados. La muestra la formaban 175 pacientes, de los cuales 134 iniciaron tratamiento con donepecilo en 5-10 mg/día y 41 con rivastigmina en 6-12 mg/día. El 20 por ciento de los pacientes presentaron AA y el 8 por ciento abandonó el tratamiento. Los trastornos gastrointestinales (TGI) fueron el principal AA observado (57,1 por ciento). El 6 por ciento de los pacientes tratados con donepecilo abandonaron el tratamiento a causa de los AA frente al 14,6 por ciento de los pacientes tratados con rivastigmina. Los pacientes tratados con rivastigmina presentaron una mayor incidencia de TGI y el riesgo relativo de presentar TGI fue 4,4 veces superior que en los pacientestratados con donepecilo. Conclusiones. Los TGI asociados al tratamiento con iACh son el principal motivo de abandono del tratamiento y se producen con mayor frecuencia en pacientes tratados con rivastigmina (AU)

Introduction. At present acetylcholinesterase inhibitors (AChEI) are used in the treatment of the cognitive deterioration associated with Alzheimer’s disease (AD). The side effects of these drugs are linked with the increase in acetylcholine, which limits their effectiveness, and must be adjusted to the patient close to the maximum tolerated dose. Patients and methods. We conducted a comparative retrospective study of the tolerance and the adverse events (AE) of two AChEI in a group of patients with very slight and mild probable AD over a 6-month period. Results. The sample was made up of 175 patients, of which 134 began therapy with 5-10 mg/day of donepezil and 41 with 6-12 mg/day of rivastigmine. 20% of the patients presented AE and 8% abandoned the treatment. Gastrointestinal disorders (GID) were the main AE observed (57.1%). Only 6% of the patients treated with donepezil abandoned the therapy because of the AE as opposed to 14.6% of the patients treated with rivastigmine. Patients treated with rivastigmine displayed a higher incidence of GID and the relative risk of presenting GID was 4.4 times higher than in the patients treated with donepezil. Conclusions. The GID associated to therapy with AChEI are the main reason for abandoning treatment and occur more frequently in patients treated with rivastigmine (AU)

[Thallium-201 scintigraphy and dobutamine echocardiography in the assessment of myocardial viability]. / Gammagrafía con talio-201 y ecocardiografía con dobutamina en la valoración de viabilidad miocárdica.

BACKGROUND: The possibility of differentiating viable from non-viable tissue among patients with severe coronary artery disease and severe left ventricular impairment entails relevant clinical and therapeutic implications since it may influence the indication of patient revascularization. To evaluate the presence of myocardial viability two techniques are available in the clinical setting: echocardiography with intravenous infusion of dobutamine and scintigraphy with myocardial perfusion with thalliem-201 by means of single-photon emission tomography. OBJECTIVE: To compare prospectively the value of these techniques for detecting viable myocardium. MATERIAL AND METHODS: Thirty-five patients with severe coronary disease and severe left ventricular dysfunction were included in the study. All patients underwent an echocardiogram using incremental doses of dobutamine, from 5 up to 40 micrograms/kg/min in three-minute periods. For thallium-201 scintigraphy the rest redistribution protocol with delayed images at 4 hours was used. The criteria for detecting viability were: a) for thallium-201, the presence of redistribution in delayed images and normal uptake at rest, and b) for dobutamine echocardiography, a sustained improvement in regional motion, biphasic response, and worsening. RESULTS: By considering the segmental improvement post-revascularization as "gold standard" of viability, the statistically significant variables in a logistic regression model and, therefore, predictors of segmental functional recovery were the biphasic response and the sustained response for dobutamine echocardiography and normal uptake at rest and redistribution in the delayed images for thallium-201. Taken together, the result was significant for the biphasic response of dobutamine echocardiography. CONCLUSIONS: The biphasic response with dobutamine echocardiography is the echocardiographic pattern that best predicts the functional recovery of the ischemic myocardium. A normal uptake and redistribution at four hours is the only scintigraphic pattern that can predict functional improvement. Of both patterns, the biphasic response is the best predictor of the functional recovery of the dysfunctional myocardium.

Gammagrafía con talio-201 y ecocardiografía con dobutamina en la valoración de viabilidad miocárdica / Thallium-201 scintigraphy and dobutamine echocardiography in the assessment of myocardial viability

Introducción y objetivo. La posibilidad de diferenciar el tejido viable del no viable en pacientes con enfermedad coronaria severa y disfunción ventricular izquierda tiene implicaciones clínicas y terapéuticas importantes, pues puede influir en la indicación de revascularización del paciente. Para poder evaluar la presencia de viabilidad miocárdica disponemos en la práctica clínica de dos técnicas: la ecocardiografía con infusión intravenosa de dobutamina y la gammagrafía de perfusión miocárdica con talio-201 mediante tomografía por emisión de fotón único. El objetivo de este estudio fue comparar de forma prospectiva el valor de estas dos técnicas en la detección de miocardio viable. Material y métodos. Se incluyeron en el estudio 35 pacientes con enfermedad coronaria y disfunción ventricular severa. A todos ellos se les realizó una ecocardiografía utilizando dosis progresivas de dobutamina desde 5 hasta 40 µg/kg/min en estadios de tres minutos. Para el talio-201 se escogió el protocolo de reposo-redistribución con imágenes tardías a las cuatro horas. Los criterios para la detección de viabilidad fueron: para el talio-201, presencia de redistribución en las imágenes tardías y la captación normal en reposo; para la ecocardiografía con dobutamina, mejoría mantenida del movimiento regional, respuesta bifásica y el empeoramiento. Resultados. Considerando como patrón oro de viabilidad la mejoría segmentaria postrevascularización, las variables que resultaron estadísticamente significativas en un modelo de regresión logística y, por tanto, predictoras de la recuperación funcional segmentaria fueron para la ecocardiografía dobutamina la respuesta bifásica y la respuesta mantenida y para el talio-201 la captación normal en reposo y redistribución en las imágenes tardías. Cuando valoramos estos patrones juntos el resultado fue significativo para la respuesta bifásica de la ecocardiografía con dobutamina. Conclusiones. La respuesta bifásica de la ecocardiografía con dobutamina es el patrón ecocardiográfico que mejor predice la recuperación funcional del miocardio isquémico. La captación normal y redistribución a las cuatro horas es el único patrón gammagráfico con capacidad de predecir mejoría funcional. De los dos patrones, la respuesta bifásica es la que mejor predice la recuperación funcional del miocardio disfuncionante (AU)

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[Comparison of dobutamine echocardiography and rest-redistribution 201-thallium SPECT in the assessment of myocardial viability taking PET as gold standard]. / Comparación entre la eco-dobutamina y talio-201 SPECT reposo-redistribución en la valoración de la viabilidad miocárdica considerando el PET como patrón oro.

BACKGROUND AND AIM: To compare Tl-201 SPECT and dobutamine stress echocardiography for the detection of myocardial viability in patients with severe left ventricular dysfunction using metabolic imaging by positron emission tomography as the standard reference. MATERIAL AND METHODS: We studied 25 consecutive patients with severe coronary artery disease and left ventricular dysfunction that underwent two different diagnostic modalities for evaluating myocardial viability: stress echocardiography with incremental doses of dobutamine from 5 up to 40 g/kg/min in 3 min stages, and 201 Tl SPECT using a rest-redistribution protocol with delayed images obtained at 4 hours. Fluorodeoxyglucose uptake by PET was used as the gold standard. Viability criteria were as follows, for 201Tl SPECT imaging: normal uptake at rest and presence of redistribution in the delayed images, for dobutamine stress echocardiography: sustained improvement and biphasic response. RESULTS: Sensitivity of thallium redistribution was 46%, for normal uptake, plus redistribution 82%, 34% for dobutamine biphasic response and 58% for sustained improvement plus biphasic response. Specificity of biphasic response was 82% and that of redistribution 67%. Stepwise logistic regression indicated that biphasic wall motion response during dobutamine stress echocardiography (2.01 CI 95%; 1.10 to 3.99) and the presence of redistribution plus normal uptake at rest with thallium imaging (2.68 CI 95%; 1.42 to 5.13) were the best predictors of viability. These results were the same when both techniques were analyzed together. CONCLUSIONS: Biphasic wall motion response during dobutamine stress echocardiography and the normal uptake plus presence of redistribution with thallium imaging were the best pre

The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.

The adhesion protein E-cadherin plays a central part in the process of epithelial morphogenesis. Expression of this protein is downregulated during the acquisition of metastatic potential at late stages of epithelial tumour progression. There is evidence for a transcriptional blockage of E-cadherin gene expression in this process. Here we show that the transcription factor Snail, which is expressed by fibroblasts and some E-cadherin-negative epithelial tumour cell lines, binds to three E-boxes present in the human E-cadherin promoter and represses transcription of E-cadherin. Inhibition of Snail function in epithelial cancer cell lines lacking E-cadherin protein restores the expression of the E-cadherin gene.

Adenomatous polyposis coli protein (APC)-independent regulation of beta-catenin/Tcf-4 mediated transcription in intestinal cells.

Alterations in the transcriptional activity of the beta-catenin-Tcf complex have been associated with the earlier stages of colonic transformation. We show here that the activation of protein kinase C by the phorbol ester PMA in several intestinal cell lines increases the levels of beta-catenin detected in the nucleus and augments the transcriptional activity mediated by beta-catenin. The response to PMA was not related to modifications in the cytosolic levels of beta-catenin and was observed not only in cells with wild-type adenomatous polyposis coli protein (APC) but also in APC-deficient cells. Binding assays in vitro revealed that PMA facilitates the interaction of the beta-catenin with the nuclear structure. Our results therefore show that beta-catenin-mediated transcription can be regulated independently of the presence of APC.