Predictors of complications and mortality following left colectomy with primary stapled anastomosis for cancer: results of a multicentric study with 1111 patients.

AIM: Reports detailing the morbidity-mortality after left colectomy are sparse and do not allow definitive conclusions to be drawn. We aimed to identify risk factors for anastomotic leakage, perioperative mortality and complications following left colectomy for colonic malignancies. METHOD: We undertook a STROBE-compliant analysis of left colectomies included in a national prospective online database. Forty-two variables were analysed as potential independent risk factors for anastomotic leakage, postoperative morbidity and mortality. Variables were selected using the 'least absolute shrinkage and selection operator' (LASSO) method. RESULTS: We analysed 1111 patients. Eight per cent of patients had a leakage and in 80% of them reoperation or surgical drainage was needed. A quarter of patients (24.9%) experienced at least one minor complication. Perioperative mortality was 2%, leakage being responsible for 47.6% of deaths. Obesity (OR 2.8, 95% CI 1.00-7.05, P = 0.04) and total parenteral nutrition (TPN) (OR 3.7, 95% CI 1.58-8.51, P = 0.002) were associated with increased risk of leakage, whereas female patients had a lower risk (OR 0.36, 95% CI 0.18-0.67, P = 0.002). Corticosteroids (P = 0.03) and oral anticoagulants (P = 0.01) doubled the risk of complications, which was lower with hyperlipidaemia (OR 0.3, P = 0.02). Patients on TPN had more complications (OR 4.02, 95% CI 2.03-8.07, P = 0.04) and higher mortality (OR 8.7, 95% CI 1.8-40.9, P = 0.006). Liver disease and advanced age impaired survival, corticosteroids being the strongest predictor of mortality (OR 21.5, P = 0.001). CONCLUSION: Requirement for TPN was associated with more leaks, complications and mortality. Leakage was presumably responsible for almost half of deaths. Hyperlipidaemia and female gender were associated with lower rates of complications. These findings warrant a better understanding of metabolic status on perioperative outcome after left colectomy.

Protocolo del estudio: abordaje del sobrepeso en Atención Primaria. Papel de la entrevista motivacional / Tackling child overweight in Primary Care: the role of motivational interviewing

Objetivo: plantear un programa de intervención sobre el sobrepeso, desarrollado por los profesionales de Atención Primaria (AP), basado en la entrevista motivacional. Analizar las variaciones del Z score del índice de masa corporal (IMC), del patrón nutricional, del nivel de actividad física y la concordancia entre dos diferentes escalas para ese fin. Metodología: diseño: estudio de intervención en niños entre 6 y 12 años que en el control del programa de salud infantil de los seis años tengan un IMC > P85 y < P95), pertenecientes a cinco consultas de Pediatría de AP. Serán excluidos los que tengan una obesidad secundaria o aquellos en los que no sea posible realizar un seguimiento adecuado. Se les realizará una intervención de seis sesiones basadas en la entrevista motivacional y se realizará una encuesta nutricional y dos de actividad física, en el momento basal, a los cuatro meses y al final de la intervención. Análisis estadístico: los factores que se asocian con los cambios pre- y posintervención se estudiarán mediante modelos de regresión multivariante. La concordancia entre las escalas de actividad física se estudiará con el índice de Kappa. Los análisis estadísticos se realizarán con el software SPSS® versión 2. Limitaciones: la falta de habilidad en la técnica de la entrevista motivacional por parte de los pediatras. Para superar dicha limitación se ha proyectado realizar un taller de formación específica a los participantes. Otra limitación es la falta de grupo control (AU)

Objective: the primary objective is to assess the impact of a programme for tackling child overweight based on motivational interviewing, by measuring changes in the body mass index Z-scores, eating patterns and physical activity levels. The agreement between two physical activity questionnaires will also be assessed. Methods: we propose to carry out an interventional study on children aged between 6 and 12 years old. All children from five paediatric doctor's lists at the participating primary care health centres identified as overweight in the 6-year-old health check-up will be candidates for this study (body mass index >85th percentile and < 95th percentile). Children with secondary obesity or those who would not be properly followed-up will be excluded from the study. A six-session intervention based on motivational interviewing, will be performed. A nutrition and physical activity questionnaire will be administered at baseline, at 4months and at the end of the intervention. Factors associated to pre-post changes will be studied via multivariate regression models. The agreement between the physical activity questionnaires will be assessed with the Kappa coefficient. Statistical analysis will be performed using SPSS version 21. The greatest limitation of this study is the lack of skills for motivational interviewing among the participating clinicians. To address this limitation, the participating clinicians will attend specific workshops on motivational interviewing focused on child obesity. Another limitation is the lack of a control group (AU)

Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE / Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group

Objetivos: El diagnóstico fotodinámico (DFD) con hexaminolevulinato se ha empezado a utilizar recientemente para mejorar la detección del cáncer vesical no músculo invasivo. Nuestro objetivo principal fue comparar el rendimiento diagnóstico de DFD frente a endoscopia con luz blanca convencional (LB) en nuestro medio. Material y métodos: Se realizó cistoscopia fluorescente con hexaminolevulinato en el momento de la RTU a 305 pacientes de 7 hospitales españoles. Todas las lesiones detectadas con LB y DFD fueron enumeradas y registradas en una base de datos online. Se analizó histopatológicamente cada lesión por separado. En 148 pacientes se tomaron además biopsias múltiples aleatorias (BMA). Resultados: Se biopsiaron un total de 1.659 lesiones: 522 identificadas con DFD y LB, 237 sólo con DFD, 19 sólo con LB y 881 BMA. De 600 neoplasias diagnosticadas DFD detectó 563, LB 441 y BMA 29 (20 CIS). La tasa media de sobredetección de DFD sobre LB fue del 31,9% globalmente, pero en el caso del CIS fue del 209%. La sensibilidad de DFD fue 93,8% y la de LB 78,2%. La especificidad de DFD fue 81,5% y la de LB 90,5%. En el 23% de los pacientes se detectó al menos una lesión neoplásica más con DFD que con LB. Conclusión: La RTU con hexaminolevulinato mejora el rendimiento diagnóstico y la calidad de la resección del cáncer vesical superficial, especialmente del CIS. La mayor sensibilidad de DFD es a costa de una menor especificidad. En nuestro estudio BMA rescató algunos falsos negativos de DFD para detectar CIS (AU)

Objectives: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. Material and methods: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. Results: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. Conclusions: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD (AU)

El papel pronóstico de la invasión perineural en la biopsia prostática / Prognostic role of perineural invasion in prostate biopsy

Introducción: A pesar de que la diseminación celular tumoral a través del sistema nervioso intraprostático se considera un mecanismo de progresión del cáncer prostático, el significado de la invasión perineural en biopsias de próstata para predecir extensión extraprostática y su utilidad como potencial factor pronóstico es controvertido. Material y métodos: Estudio retrospectivo llevado a cabo en una institución sobre 208 pacientes tratados con prostatectomía radical (enero 2007-julio 2010) en los que se ha determinado la presencia de invasión perineural y el score de gleason en la biopsia preoperatoria, así como el estadio clínico y el PSA prequirúrgico. Clasificamos los pacientes en grupos de riesgo según la clasificación de D’Amico. Realizamos análisis estadístico bivariante y multivariante para establecerla correlación entre las distintas variables. Resultados: Se objetivó IPN en el 18,3% de las biopsias prostáticas. Presentaron extensión extraprostática el 71% de los espécimenes de prostatectomía con invasión perineural en la biopsia previa vs. 23,1% cuando no existía este hallazgo (p < 0,0001) y márgenes positivos el 47,4% de los casos con IPN, frente a 18,3% sin invasión perineural (p < 0,0001). De hecho, en el análisis multivariante la invasión perineural demostró ser un factor de riesgo independiente para presentar extensión extraprostática y márgenes positivos en la pieza de prostatectomía. Conclusiones: La presencia de Invasión perineural es un factor pronóstico útil para la predicción de extensión extraprostática y afectación de márgenes quirúrgicos en la pieza de prostatectomía radical. Consideramos que su determinación puede ser una herramienta útil en la mejora del diagnóstico preoperatorio y en la planificación del tratamiento (AU)

Introduction: Despite tumour cell dissemination through the intraprostatic nervous systembeing considered as a prostate cancer progression mechanism, the significance of perineural invasion in prostate biopsies to predict extraprostatic extension and its use as a potential prognosis factor is controversial. Materials and methods: Retrospective study carried out at an institution on 208 patients treated with radical prostatectomy (January 2007 - July 2010) in which the presence of perineural invasion and the Gleason score in the preoperative biopsy were determined, as well as the clinical stage and the pre-surgery PSA. We classified the patients in risk groups in accordance with the D’Amico classification. We performed bivariate and multivariate statistical analyses to establish the correlations between the different variables. Results: We objectified PNI in 18.3% of the prostate biopsies. 71% of the prostatectomy specimens with perineural invasion presented extraprostatic extension in the previous biopsy against 23.1% when this was not found (p < 0.0001) and 47% of the cases showed positive margins with PNI, against 18.3% without perineural invasion (p < 0.0001). In fact, in the multivariate analysis, perineural invasion proved to be an independent risk factor in the presentation of extraprostatic extension and positive margins in the prostatectomy specimen. Conclusions: The presence of perineural invasion is a useful prognostic factor for predicting extraprostatic extension and the involvement of surgical margin in the radical prostatectomy specimen. We believe that determining it may be a useful tool for improving preoperative diagnosis and planning treatment (AU)

[Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group]. / Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE.

OBJECTIVES: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. MATERIAL AND METHODS: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. RESULTS: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. CONCLUSIONS: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.

[Prognostic role of perineural invasion in prostate biopsy]. / El papel pronóstico de la invasión perineural en la biopsia prostática.

INTRODUCTION: Despite tumour cell dissemination through the intraprostatic nervous system being considered as a prostate cancer progression mechanism, the significance of perineural invasion in prostate biopsies to predict extraprostatic extension and its use as a potential prognosis factor is controversial. MATERIALS AND METHODS: Retrospective study carried out at an institution on 208 patients treated with radical prostatectomy (January 2007 - July 2010) in which the presence of perineural invasion and the Gleason score in the preoperative biopsy were determined, as well as the clinical stage and the pre-surgery PSA. We classified the patients in risk groups in accordance with the D'Amico classification. We performed bivariate and multivariate statistical analyses to establish the correlations between the different variables. RESULTS: We objectified PNI in 18.3% of the prostate biopsies. 71% of the prostatectomy specimens with perineural invasion presented extraprostatic extension in the previous biopsy against 23.1% when this was not found (p<0.0001) and 47% of the cases showed positive margins with PNI, against 18.3% without perineural invasion (p<0.0001). In fact, in the multivariate analysis, perineural invasion proved to be an independent risk factor in the presentation of extraprostatic extension and positive margins in the prostatectomy specimen. CONCLUSIONS: The presence of perineural invasion is a useful prognostic factor for predicting extraprostatic extension and the involvement of surgical margin in the radical prostatectomy specimen. We believe that determining it may be a useful tool for improving preoperative diagnosis and planning treatment.

Métodos no invasivos de valoración de la inflamación de la víaaérea / Non-invasive methods of evaluation of the inflammation of the airway

La respuesta inflamatoria es un mecanismo de defensa, deadaptación biológica del organismo ante las agresiones internas oexternas, que pretende devolver la situación basal al mismo unavez eliminados los agentes nocivos y reparadas o cicatrizadas lasestructuras afectadas por la agresión. Enfermedades tan prevalentescomo asma, rinitis, y enfermedad pulmonar obstructiva crónica(EPOC) tienen su sustrato en la inflamación, y su estudio constituyeuno de los aspectos de mayor interés en el campo de la biologíay la medicina. Esta novedosa visión de la patología respiratoriaha suscitado el interés por el desarrollo de métodos que, de formatotalmente no invasiva, nos permitan monitorizar dicha inflamacióny, al mismo tiempo, conocer con mayor detalle los aspectosmás íntimos de los mecanismos subyacentes a diversas enfermedadesde la vía aérea. Con este artículo de revisión se pretende abordarde forma práctica y clara el estado actual de los conocimientosacerca de la inflamación, de las diversas técnicas y biomarcadoresa nuestro alcance para objetivar la magnitud de esa inflamación, yde su utilidad desde el punto de vista clínico asistencial, y no solamenteen el campo de la investigación

The inflammatory response is a defence mechanism of biologicaladaptation of the organism against internal or external aggressions,which attempts to return to the baseline situation as soon asthe harmful agents are eliminated and the structures affected bythe aggression repaired or scarred. Illnesses as prevalent asasthma, rhinitis, and chronic obstructive pulmonary disease(COPD) have their root cause in inflammation, and its study constitutesone of the major aspects of interest in the fields of Biologyand Medicine. This novel vision of respiratory pathology hascaused the interest in the development of methods that allow us tomonitor this inflammation in a completely non invasive mannerand, at the same time, to know the most intimate aspects of theunderlying mechanisms of diverse illnesses of the airway withgreater detail. This review article of the current state of knowledgeattempts a clear and practical approach about inflammation, andthe diverse techniques and biomarkers at our disposal to assess themagnitude of this inflammation, and their utility not only in thefield of research but also with regard to clinical welfare

Generation and characterization of monoclonal antibodies to the neural crest.

The generation of monoclonal antibodies (MAbs) specific for quail neural crest may provide valuable tools for studying the differentiation of embryonic precursor cells. Unfortunately, relatively few antibodies are available because of the difficulty in obtaining sufficient cells for in vivo immunization strategies. We have overcome this problem by using intrasplenic immunization with formaldehyde-fixed cells harvested from neural crest cultures. In addition, booster injections of cultured whole-embryo cells were administered intraperitoneally. Following two fusions, a total of 18 hybridomas were generated with antibody reactivity to the cytoplasm of neural crest cells. Furthermore, 32 were reactive against both somite (a noncrest mesodermal control) and crest cultures, whilst 15 were not reactive. Out of those hybridomas reactive with neural crest, six designated 160D, 164D, OE, 12E, 120E and 124E were further characterized. Interestingly MAb supernatants OE, 12E, 120E, and 124E exhibited reactivity against some but not all neural crest cells suggesting that they might recognise subpopulations. Immunoglobulin isotyping of supernatants revealed that 4 (160D, 164D, OE, and 120E) were IgM and 2 (12E and 124E) were IgG(2b). On assessing their reactivity against human tissue sections, all six hybridoma supernatants cross-reacted with neuroendocrine cells within appendix, colon and rectum. These MAbs could provide novel reagents for the understanding of neural crest development.

Asma bronquial. Correspondencia entre dos clasificaciones según su gravedad

Se realiza una investigación de tipo descriptiva en cinco Consultorios Médicos de Familia pertenecientes al Policlínico “Capitán Roberto Fleites”, en Santa Clara, Cuba, durante el período de enero a diciembre de 1999. Se toman para el estudio a 41 pacientes asmáticos con edades comprendidas entre 5 y 14 años. Primero se clasifica a estos pacientes or los parámetros de Kraeppelin, según la frecuencia e intensidad de las crisis en el año precedente y después esos mismos pacientes son clasificados teniendo en cuenta, además del patrón clínico, la medición del Flujo Espiratorio Pico (FEP), haciéndose una comparación de los resultados de ambas clasificaciones para establecer el grado de concordanciaentre ambas. Un 36,6 por ciento de los pacientes presentaron un FEP obstructivo. El porcentaje de concordancia fue del 70,8 por ciento. A pesar de esas diferencias, no podemos señalar estadísticamente que no existe concordancia en nuestra casuística. Se propone el uso de la Clasificación clínico-funcional en la evaluación del paciente asmático siempre que se disponga de los medios necesarios y aumentar la disponibilidad y uso de los medidores manuales de FEP en Atención Primaria(AU)

Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate.

Glucocorticoid receptor (GR) activation induces apoptosis of granule cells in the hippocampus. In contrast, neuroprotection is seen after mineralocorticoid receptor (MR) activation. To date there is no in vivo evidence for direct interactions between corticosteroids and any of the key regulatory molecules of programmed cell death. In this report, we show that the opposing actions of MR and GR on neuronal survival result from their ability to differentially influence the expression of members of the bcl-2 gene family; specifically, in the rat hippocampus, activation of GR induces cell death by increasing the ratio of the proapoptotic molecule Bax relative to the antiapoptotic molecules Bcl-2 or Bcl-x(L); the opposite effect is observed after stimulation of MR. The same results were obtained in both young and aged animals; however, older subjects (which were more susceptible to GR-mediated apoptosis) tended to express the antiapoptotic genes more robustly. Using a loss-of-function mouse model, we corroborated the observations made in the rat, demonstrating Bax to be essential in the GR-mediated cell death-signaling cascade. In addition, we show that GR activation increases and MR activation decreases levels of the tumor suppressor protein p53 (a direct transcriptional regulator of bax and bcl-2 genes), thus providing new information on the early genetic events linking corticosteroid receptors with apoptosis in the nervous system.

Central LPS-induced c-fos expression in the PVN and the A1/A2 brainstem noradrenergic cell groups is altered by adrenalectomy.

The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipopolysaccharide (LPS). The mechanisms underlying such activation and differences between alternative routes of administration remain unclear. We examined activation of the PVN and A1/A2 cell groups, by assessing c-fos mRNA, or counting Fos-positive neurons in either the PVN or in brainstem A1/A2 cell groups 3 h after intracerebroventricular (i.c.v.) LPS, in control and adrenalectomized (ADX) rats. We also measured corticotropin-releasing hormone (CRH) mRNA in the PVN, and plasma corticosterone (CORT) levels. A group of ADX/CORT-replaced animals received i.c.v. LPS, and CRH mRNA and Fos peptide in the PVN were analysed. ADX increased CRH mRNA in the PVN, as did LPS, but no enhancement of this response was seen in LPS/ADX animals. C-fos mRNA also increased in both the PVN and the A2 cell group following LPS, but this response was potentiated by ADX. Fos peptide-containing cells increased in the PVN and A2 following LPS, and this change was amplified by ADX. Only 11.25% of Fos was found in DBH-positive (putative noradrenergic) neurons, suggesting activation of neurons containing other transmitters. ADX/LPS/CORT animals showed numbers of Fos neurons in the brainstem, and CRH mRNA levels in the PVN which were comparable to intact/LPS animals. Central LPS activates the hypothalamo-pituitary-adrenal axis, a process mediated partly by brainstem noradrenergic neurons, suggesting the involvement of afferent/efferent pathways within the brain. Peripheral administration of LPS involves activation of vagal inputs leading to the nucleus tractus solitarius. We suggest that centrally administered LPS activates the A2 cell group by a mechanism independent of the vagus. In the absence of CORT, despite the lack of a CRH mRNA response, an exaggerated c-fos and peptide response to LPS is observed, which is reversed following CORT pretreatment.

Serotonin depletion does not alter lipopolysaccharide-induced activation of the rat paraventricular nucleus.

We have investigated the effects of serotonin depletion on immune-mediated activation of the hypothalamo-pituitary-adrenal (HPA) axis. Corticotrophin-releasing factor (CRF) mRNA, c-fos mRNA and Fos peptide responses in the paraventricular nucleus (PVN) together with circulating levels of corticosterone were assessed in response to i.p. injections of three doses of lipopolysaccharide (LPS) both in control animals and animals pretreated with p-chlorophenylalanine (PCPA). Conscious animals received either an i.p. injection of 0.5 ml saline or 200 mg/kg PCPA in 0.5 ml saline on 2 consecutive days. This treatment resulted in a 93% depletion of serotonin on the fourth day. On day 4, animals received i.p. injections of LPS (2.5 mg/0.5 ml saline, 250 micrograms/0.5 ml or 50 micrograms/0.5 ml; E. coli 055:B5), or saline injections as controls. Pretreatment with PCPA had no effect on the basal levels of corticosterone, or on the elevated levels induced by the three doses, of LPS. Fos peptide and c-fos mRNA were undetectable in control animals, and Fos-like immunoreactivity increased in a dose-dependent manner following i.p. LPS in both control and PCPA-pretreated animals. C-fos mRNA expression induced by LPS was unaffected by serotonin depletion. Following the lowest dose of LPS, CRF mRNA did not change above control levels, however, the medium and high doses of LPS produced a significant (P < 0.05) increase in CRF mRNA levels in both depleted and intact animals. To confirm the temporal effects of serotonin depletion on activation of the HPA axis we collected plasma at 30 min, 1, 2, 3, 4, 5, and 6 h after LPS in both intact and serotonin-depleted animals. No significant differences in plasma corticosterone levels were found at any of the time points between intact and depleted animals. It appears that, at least under these experimental conditions, serotonergic inputs do not seem to play a major role in mediating the effects of LPS on changes in mRNA levels in the PVN or on the subsequent activation of the HPA axis.

The hypothalamic-pituitary-adrenal axis in autoimmunity.

We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. We have good evidence to suggest that AVP takes over as the major stimulator of the axis. The arthritic rat is unable to mount a response to acute stressors, such as restraint or ip hypertonic saline. However, these animals are able to mount a response to an acute immune challenge. These data provide further evidence for a differential activation of the HPA by acute stress or acute immune stimulation. This presumably reflects an adaptive response to the development of chronic inflammation. We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.

Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity.

The behavioural and endocrine responses to a 10 min white noise stress have been characterized in female virgin and undisturbed lactating Sprague-Dawley rats. Animals were continuously video-taped and frequent blood samples were collected using an automated sampling system. Noise stress caused hypothalamo-pituitary-adrenal (HPA) activation, as indicated by a rapid increase in plasma corticosterone and ACTH in the virgins: corticosterone concentrations peaked 20 min after initiation of the stress before declining rapidly back to basal concentrations. In contrast, noise stress had no significant effect on either plasma corticosterone or ACTH concentrations in the lactating animals. However, 72 h after weaning the corticosterone response of the ex-lactating rats was of comparable magnitude, but longer duration to that seen in the virgins. Plasma prolactin concentrations were significantly higher in the lactating animals and declined in response to the noise whereas, a transient but reproducible increase was seen in the virgin group. In situ hybridization revealed a significantly lower basal expression of CRF mRNA in the paraventricular nucleus of lactating rats as compared to the virgins, but noise stress had no further effect. Virgin animals showed behavioural responses to the stress, including an increase in the total activity, exploratory behaviours (rearing) and displacement behaviours (grooming). Lactating animals also showed behavioural responses to the noise, but their activities were principally directed towards the pups. These data show that although lactating rats showed normal behavioural reactivity to a psychological stress they showed no statistically significant activation of the HPA axis, suggesting a dissociation of behavioural and neuroendocrine responses to this mild stress.

Interleukin-1 beta-induced effects on plasma oxytocin and arginine vasopressin: role of adrenal steroids and route of administration.

The effects of cytokines in stimulating neurohypophysial hormone release have not been well characterized. In the present study, we have investigated the effect of intraperitoneal injection of recombinant human interleukin (IL)-1 beta on oxytocin release in sham-operated controls, adrenalectomized (ADX) rats and ADX rats given either low or high doses of the synthesis glucocorticoid dexamethasone. In a second study, we determined the effect of central injection of IL-1 beta on both oxytocin and arginine vasopressin (AVP) release in sham-operated and ADX rats. We were unable to demonstrate an increase in plasma oxytocin in intact rats in response to intraperitoneal injection of IL-1 beta. In contrast, we found a substantial and sustained increase in plasma oxytocin concentrations in ADX rats. This stimulation was abolished by treatment with dexamethasone at both the low and high doses. Following central injection of IL-1 beta, we were unable to demonstrate any increase in either oxytocin or AVP, despite the ability of this dose of cytokine to stimulate the hypothalamo-pituitary-adrenal axis, as evidenced by increased circulating corticosterone. It appears that circulating glucocorticoids may exert a tonic inhibitory effect on the release of oxytocin in response to peripheral stimulation by IL-1 beta.

Persistent transgene expression in the hypothalamus following stereotaxic delivery of a recombinant adenovirus: suppression of the immune response with cyclosporin.

Replication deficient, recombinant adenoviruses (Ads) have been used successfully to transfect several forebrain and brainstem nuclei, but have yet to be demonstrated as useful vectors for transgene delivery in the structurally diverse and highly vascularised nuclei of the hypothalamus. In the present study we have assessed the ability of an Ad expressing the lac-Z gene to transfect cells of the paraventricular nucleus (PVN) of the hypothalamus in vivo. We show that: (1) we can achieve stable expression of the lacZ gene in cells of the magnocellular PVN for at least 2 months; (2) there were no obvious differences in the level of AVP mRNA in the PVNs injected with Ad compared with those injected with vehicle suggesting that Ad treatment is not disrupting normal cellular function in the injection region; (3) the introduction of Ads results in a limited immune response; (4) systemic treatment with cyclosporin dramatically reduces its magnitude. We conclude that Ad vectors represent useful tools for neuroendocrinological and gene therapeutic studies of the hypothalamus.

Estrogen uncouples noradrenergic activation of Fos expression in the female rat preoptic area.

The preoptic area of the rat brain is a site at which gonadal steroids act to regulate sexual behaviour and gonadotrophin secretion. The expression of the immediate-early gene product, Fos, in the preoptic area was investigated in conscious ovariectomised, vehicle and estrogen-treated animals which had received an intracerebroventricular (i.c.v.) infusion of noradrenaline, and also in anaesthetised proestrous and ovariectomised rats following electrical stimulation of the brainstem A1 or A2 noradrenergic cell groups. In ovariectomised oil-treated rats, a third ventricular infusion of noradrenaline (45 micrograms) resulted in a significant (P < 0.05) increase in the numbers of Fos-immunoreactive cell nuclei throughout the preoptic area, compared to vehicle controls. In contrast, Fos expression in animals which had received estrogen replacement showed no change in response to i.c.v. noradrenaline compared with saline-treated controls. In anaesthetised, ovariectomised animals electrical stimulation of the A1 cell group resulted in a significant increase (P < 0.05) in Fos-like immunoreactivity compared with sham controls, specifically within the ventral preoptic area whilst stimulation of the A2 cell group had no significant effect. In anaesthetised, proestrous rats receiving electrical stimulation no significant changes in Fos-like immunoreactivity were detected within the preoptic area after either A1 or A2 stimulation compared with paired controls. These results show that noradrenaline-induced Fos expression in the preoptic area is dependent on estrogen status and suggest that the estrogenic regulation of reproductive functions may thus involve altered responses to noradrenaline in sub-populations of preoptic neurones.

[Pancreatitis caused by hypercalcemia of malignant origin]. / Pancreatitis por hipercalcemia de origen maligno.

Malignant hypercalcemia is seldom the cause of an acute pancreatitis; this complication is more frequent when hypercalcemia is due to hyperparathyroidism. We present a case of acute pancreatitis triggered by a malignant hypercalcemia as the first sign of the neoplastic process. Solid tumors with bone extension can produce hypercalcemia and may be the origin of hypercalcemic pancreatitis.

Changing patterns of Fos expression in brainstem catecholaminergic neurons during the rat oestrous cycle.

Brainstem catecholaminergic neurons are believed to play an important role in the activation of luteinising hormone-releasing hormone (LHRH) neurons on the afternoon of proestrus which results in the luteinising hormone (LH) surge. To examine the respective roles of brainstem A1 and A2 neurons and the adjoining C1 and C2 adrenergic cells at this time, we have examined the patterns of Fos-immunoreactivity within tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) neurons during diestrus and proestrus. Initial studies demonstrated that the LH surge commenced at approximately 15:00 h in proestrous animals and that peak plasma levels of LH were observed between 16:00 and 17:00 h. Groups of cycling female rats (n = 6) were then perfused between 09:00 and 11:00 (diestrus early) and 18:00 to 19:30 h (diestrus late) on diestrus and at the same times on proestrus (proestrus early and proestrus late). Double-labelling immunocytochemistry revealed little Fos expression by adrenergic neurons of the C1 or C2 cell groups and this did not change significantly between any of the experimental groups. Analysis of the A2 region was divided into rostral, middle and caudal divisions and all regions showed a significant (P < 0.01) increase in the number of Fos-expressing TH neurons (up to 35% of TH cells) in proestrus early animals compared with diestrus and proestrus late rats. In the A1 region, a significant increase in the number of TH neurons expressing Fos (approximately 33%) was detected in both proestrus early (P < 0.05) and diestrus early (P < 0.01) rats compared with animals perfused in the late afternoon (approximately 12%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Muscular tumors of the digestive tract]. / Tumores musculares del tracto digestivo.

We report the experience of the General Surgery Service of Segovia General Hospital. In a 15-years-period (1976-1991), we have cared for 32 patients with muscular tumors of the gastrointestinal tract, including 22 leiomyomas and 11 leiomyosarcomas. These tumors were localized in stomach (46.8%), small intestine (40.6%), esophagus (9.3%) and colon-rectum (3.1%). A histologic study was developed on the basis of the mitosis number in 10 high power fields. Clinical manifestations, histological dates, treatment, and prognosis factors, outstanding the histological grade, size lesser than 10 cm, and tumor origin localization, are reviewed.