Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma / Uso del Conjunto Mínimo Básico de Datos (CMBD), como instrumentode vigilancia epidemológica del mesotelioma

Background:Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma. Methods:Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out.Results:The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez. Conclusion:The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.(AU)

Fundamento: El mesotelioma es un tumor muy agresivo que surge tras varias décadas de exposición al amianto. El Conjunto Mínimo Básico de Datos (CMBD), ha sido validado para conocer la incidencia del mesotelioma en Italia, pero no en España. El objetivo de este trabajo es conocer la prevalencia, incidencia y mortalidad por mesotelioma en la Comunidad de Madrid (CM), evaluar la distribución del riesgo dentro de su territorio y explorar la validez del CMBD en la vigilancia epidemiológica del mesotelioma en España. Material y métodos: Se han utilizado los datos del CMBD de la CM con diagnóstico de mesotelioma y las causas de muerte registradas en el Instituto Nacional de Estadística (INE), durante el periodo 2016-2017. Los cálculos de tasas ajustadas, de distribución geográfica de casos y fallecidos, y de correlación del patrón geográfico a nivel municipal entre ambas fuentes (CMBD eINE), se realizaron mediante los programas R y Excel. Resultados: La incidencia del mesotelioma en la CM fue más alta en 2016 y 2017 que en años precedentes. La mortalidad calculada (INE) y la estimada (CMBD) fueron similares. La correlación entre patrones geográficosde riesgo obtenidos mediante CMBD e INE fue elevada (r = 0.86). La agregación de casos continúa concentrándose en los municipios del sur de la CM, detectándoseel máximo riesgo en Aranjuez. Conclusiones: Tanto el CMBD como el INE representan fuentes adecuadas para monitorizar el riesgo de mesotelioma. Se precisa de nuevos estudios que expliquen laagregación de casos detectada en Aranjuez.(AU)

Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma.

BACKGROUND: Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma. METHODS: Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out. RESULTS: The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez. CONCLUSION: The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.

Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.

Oligomers of ß-amyloid protein (Aß1-42) induce the activation of cyclooxygenase-2 in astrocytes via an interaction with interleukin-1ß, tumour necrosis factor-α, and a nuclear factor κ-B mechanism in the rat brain.

Despite growing evidence indicating the effects of cytokines, including interleukin-1beta (IL-1ß) and tumour necrosis factor-α (TNFα), and the enzyme cyclooxygenase-2 (COX-2) in Alzheimer's diseases, little is known about the signalling mechanisms that mediate its activation in response to beta-amyloid protein (Aß). The aim of this study was first to investigate whether Aß1-42 peptide induced the up-regulation of COX-2. We then examined the expression of COX-2 and cytokines, such as IL-1ß and TNFα, in reactive astrocytes. Finally, we analyzed the role of nuclear factor kappa-B (NF-κB) as a signalling pathway in early stages of Aß-toxicity. In Wistar rats anaesthetised with equitesine, a single microinjection of Aß1-42 oligomers was made in the left retrosplenial cortex. Control animals were injected with Aß42-1 peptide into the corresponding region of the cerebral cortex. By COX-2 immunoblotting, we detected two immunopositive protein bands, at 70 and 50 kDa molecular mass. In the Aß1-42-injected animals the 50 kDa fragment showed a significant increase at 3 and 14 days, as compared with that seen in control animals. The 70 kDa fragment showed a maximal increase at 14 days. In the Aß1-42-injected animals immunoblot staining of NF-κB detected an active protein band at 50 kDa molecular mass, showing a maximal increase at the 72 h time point. Confocal analysis revealed that COX-2 protein co-localized with Aß-IR material at the injection site and in endothelial blood vessels, increasing at 72 h. In the Aß oligomer-treated animals, COX-2, IL-1ß, and TNFα proteins were expressed in reactive astrocytes surrounding the injection site and blood vessels at early stages of Aß toxicity. Double-labelling immunofluorescence studies also revealed that GFAP and COX-2 proteins co-localized with NF-κB-positive material at early time-points. In conclusion, our results suggest that in reactive astrocytes and in COX-2 positive cells NF-κB may mediate pro-, and/or inflammatory gene expression and that, develop strategies that target the GFAP/NF-κB and COX-2/NF-κB pathways might contribute to reducing Aß-induced toxicity.

Cáncer infantil de origen ocupacional: leucemias y linfomas / Childhood cancer of occupations origin: leukemia and lymphomas

Entre lo niños de edades comprendidas entre 5-12 años el cáncer es la segunda causa de mortalidad, precedida solo por los accidentes, y en el grupo de edad de 1-4 años es la 3º causa de mortalidad, después de accidentes y anomalías congénitas. La leucemia es el tipo de cáncer más común entre los niños, con un pico de incidencia entre los 2 y 4 años. El 80% de leucemias a esta edad son del tipo leucemia linfoblástica aguada (LLA). En los últimos años se han revisado factores de riesgo, que incluyen: factores genéticos, características al nacimiento, exposición prenatal a hormonas exógenas, radiaciones prenatales, infecciones virales y radiaciones postnatales. Más recientemente, numerosos estudios han sugerido que la exposición ocupacional de los padres puede estar implicada en la etiología del cáncer infantil. Nosotros hemos realizado una revisión bibliográfica de la literatura sobre estudios observacionales, revisiones sistemáticas y meta-análisis en relación con la exposición ocupacional paterna/materna a pesticidas, solventes, colorantes, petróleo y sus derivados, plomo y componentes de plomo, polvo orgánico, polvo de madera, radiaciones, campos electromagnéticos y otros posibles agentes carcinogénicos como factores de riesgo para el desarrollo posterior de leucémica y linfoma infantil (AU)

Among children between the ages of 5 and 14 years, cancer is the second cause of death, preceded only by accidents, and in the age group of 1 and 4 years, it is the tried cause of death after accidents and congenital anomalies. Leukaemia is the most common cancer among children with a peak incidence between 2 and 4 years old. Almost 80% of the leukaemias in this age group are of the acute lymphoblastic type. In the last few years, risk factors have been reviewed which include: genetic factors, birth characteristics, prenatal exposure to exogenous hormones, irradiation, viral infections and postnatal irradiation. More recently, several studies have suggested that occupational exposure of parents may be involved in the etiology of childhood cancer. We have performed a review of the literature on observational studies, systematic reviews and meta-analysis in relation to paternal/maternal occupational exposure to pesticides, solvents, dyes, petroleum and petroleum products, lead and lead compounds, organic dust, powder wood, radiation fields and other potencial carcinogens as risk factors for later development of leukaemia and lymphoma in children (AU)

Cáncer infantil de origen ocupacional: neuroblastoma y tumores del SNC / Childhood cancer of occupational origin: neuroblastoma and CNS tumors

Numerosos estudios han sugerido que la exposición ocupacional paterna y materna a diferentes sustancias químicas y campos electromagnéticos, puede tener un papel en la etiología del cáncer infantil. La aparición en edades muy tempranas de los casos de cáncer infantil puede estar relacionado con factores etiológicos que influyan en la concepción, embarazo y primera infancia, tales como la ocupación parental. Por su frecuencia en la infancia vamos a centrarnos en los estudios que relacionan la exposición ocupacional parental con la parición de neuroblastoma y tumores del SNC en la descendencia (AU)

Numerous studies have suggested that paternal pre-conceptional occupational exposures may have a role in the aetiology of childhood cancers. Because a remarkable number of childhood cancers occur at very young ages, it has been hypothesized than causes may operate during the prenatal and neonatal period, like parental occupational exposure. Due to the frequency in childhood, we review the studies that establish a relation between occupational exposure in parents and cases of neuroblastoma and central nervous system tumours in offspring (AU)

Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain.

OBJECTIVES: There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. METHODS: This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. RESULTS: The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains. CONCLUSIONS: H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.

Soluble oligomeric forms of beta-amyloid (Abeta) peptide stimulate Abeta production via astrogliosis in the rat brain.

The aim of this study was to investigate the interaction between beta-amyloid (Abeta) peptide and astrogliosis in early stages of Abeta toxicity. In Wistar rats, anaesthetised with equitesine, a single microinjection of Abeta1-42 oligomers was placed into the retrosplenial cortex. Control animals were injected with Abeta42-1 peptide into the corresponding regions of cerebral cortex. Immunocytochemical analysis revealed an intense Abeta immunoreactivity (IR) at the level of Abeta1-42 injection site, increasing from the first 24 h to later (72 h) time point. Control injection showed a light staining surrounding the injection site. In Abeta oligomers-treated animals, Abeta-immunopositive product also accumulates in cortical cells, particularly in frontal and temporal cortices at an early (24 h) time point. Abeta-IR structures-like diffuse aggregates forms were also observed in hippocampus and in several cortical areas, increasing from the first 24 h to later (72 h) time point. In control animals no specific staining was seen neither in cortical cells nor in structures-like diffuse aggregates forms. Injections of Abeta oligomers also induce activation of astrocytes surrounding and infiltrating the injection site. Astrocyte activation is evidenced by morphological changes and upregulation of glial fibrillary acidic protein (GFAP). By GFAP immunoblotting we detected two immunopositive protein bands, at 50 and 48 kDa molecular mass. Confocal analysis also showed that GFAP co-localized with Abeta-IR material in a time-dependent manner. In conclusion, our results indicate that astrocyte activation might have a critical role in the mechanisms of Abeta-induced neurodegeneration, and that should be further studied as possible targets for therapeutic intervention in AD.

Beta-amyloid peptide-induced modifications in alpha7 nicotinic acetylcholine receptor immunoreactivity in the hippocampus of the rat: relationship with GABAergic and calcium-binding proteins perikarya.

The effects of the injected beta-amyloid (Abeta) protein on the alpha7 subtype of nicotinic acetylcholine receptor protein (alpha7nAChR) in the hippocampus were studied in rats. Injections of Abeta into the retrosplenial cortex resulted in a decrease in alpha7nAChR-immunoreactivity in the hippocampus. Quantitative analysis revealed a significant reduction in alpha7nAChR-immunoreactivity in the dorsal part of the CA1 ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that seen in the contralateral hemisphere, which corresponds to the control (PBS)-injected side. A significant decrease in alpha7nAChR-immunoreactivity was also found in the dorsal part of the ipsilateral CA1 as compared with that in the ventral part of the CA1, in CA2, and in CA3 ipsilateral to the Abeta-injected side. The analysis also revealed a significant decrease in alpha7nAChR-immunoreactivity in the dentate gyrus ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that in the PBS-injected side co-localization studies showed that the alpha7nAChR protein is highly localized in GABA- and Parv-immunoreactive cells, while only few Calb-positive cells expressed immunoreactivity for alpha7nAChR. In addition, injections of Abeta protein resulted in a significant reduction in the number of GABA- and Parv-immunoreactive cells in the dorsal part of the ipsilateral CA1 as compared to the corresponding region of non-treated control animals and with that in the corresponding region of the PBS-injected side. Our findings suggest that Abeta induces a reduction in alpha7nAChR-containing cells, which may contribute to impairment of GABAergic synaptic transmission in the hippocampus.

Effects of beta-amyloid protein on serotoninergic, noradrenergic, and cholinergic markers in neurons of the pontomesencephalic tegmentum in the rat.

The effects on serotoninergic, noradrenergic and cholinergic markers on neurons of the pontomesencephalic tegmentum nuclei were studied in rats following local administration of fibrillar beta-amyloid peptide (Abeta1-40) into the left retrosplenial cortex. Focal deposition of Abeta in the retrosplenial cortex resulted in a loss of serotoninergic neurons in the dorsal and median raphe nuclei. The dorsal raphe nucleus showed a statistically significant reduction of 31.7% in the number of serotoninergic neurons and a decrease (up to 17.38%) in neuronal density in comparison with the same parameters in uninjected controls. A statistically significant reduction of 50.3%, together with a significant decrease of 53.94% in the density of serotoninergic neurons, was also observed in the median raphe nucleus as compared with control animals. Furthermore, a significant reduction of 35.07% in the number of noradrenergic neurons as well as a statistically significant decrease of 56.55% in the density of dopamine-beta-hydroxylase-immunoreactive neurons were also found in the locus coeruleus as compared with the corresponding hemisphere in uninjected controls. By contrast, a reduction of 24.37% in the number of choline acetyltransferase-positive neurons and a slight decrease (up to 22.28%) in the density of cholinergic neurons, which were not statistically significant, was observed in the laterodorsal tegmental nucleus in comparison with the same parameters in control animals. These results show that three different neurochemically defined populations of neurons in the pontomesencephalic tegmentum are affected by the neurotoxicity of Abeta in vivo and that Abeta might indirectly affect serotoninergic, noradrenergic and cholinergic innervation in the retrosplenial cortex.

Aspiration cytology of 147 adnexal cysts with histologic correlation.

OBJECTIVE: To assess the usefulness of cytology in the diagnosis of 147 histologically established adnexal cysts. STUDY DESIGN: Retrospective, macro-microscopic study based on fluid aspirated from 132 ovarian and 15 extraovarian cysts and projected as a cytohistologic correlation. RESULTS: Typical macroscopic features were identified in 76% of endometriotic cysts, in 53% of mucinous neoplasms and in 67% of dermoid cysts. Cytology helped to identify 67% of nonneoplastic and 56% of neoplastic cysts. The lowest diagnostic sensitivities were observed in functional cysts and benign serous neoplasms (50%), while the highest were shown by endometriotic cysts (76%) and malignant epithelial neoplasms (71%). Inadequate samples were obtained from all types of cysts, even malignant ones (two mucinous cystadenocarcinomas). Diagnostic cytology was useless in extraovarian cysts (33% sensitivity). An adult granulosa cell tumor was erroneously diagnosed as a follicular cyst by cytologic examination. CONCLUSION: Examination of the cyst fluids obtained by aspiration demonstrated low sensitivity, with 43% of inadequate samples obtained from all types of cysts. Malignant cystic neoplasms may be overlooked in inadequate samples. Our study also revealed that specificity in this type of analysis is high in inadequate samples, provided that the technique is carried out correctly.

Consumption of wine stored in leather wine bottles and incidence of gastric cancer.

The authors conducted a survey among participants of a large-scale case-control study to evaluate a possible association between consumption of wine in leather bottles and incidence of gastric cancer. There were 59 cases and 53 controls in the study. The results suggest that some of the components of the complex mixture (i.e., tar) used in the proofing of leather wine bottles might dissolve in the wine and participate in the etiology of gastric cancer. Nevertheless, the results should be confirmed in an independent study.

Sex as a prognostic factor in gastric cancer.

The aim of this study was to assess whether survival of gastric cancer patients differed between males and females. Although it is well known that the incidence of gastric cancer is higher for men than for women, the existence of a sex-specific prognosis has seldom been addressed. Studies based on population registries have not assessed the role of stage and histology. Cases of histologically confirmed gastric carcinoma were obtained from three Spanish hospitals in Soria (n = 405), Barcelona (n = 249) and Mataró (n = 197). Differences in possible confounders were tested between men and women and survival analyses were performed separately by hospital. Cox's proportional hazards models were used to account for age, tumour stage, histology and tumour sub-location. Only in Mataró was a significant difference in the stage distribution observed between women and men, with a lower proportion of local stage tumours among women (P = 0.047). No statistically significant differences of histological type between men and women were observed in any of the centres. After adjusting for tumour stage and age, women were observed to have significantly better survival in Barcelona (female to male hazard ratio (HR) = 0.578, P < 0.001); this effect was marginal in Soria (HR = 0.788, P = 0.092) and non-significant in Matar-o (HR = 0.895, P = 0.54). Age-adjusted hazard ratios were calculated within each tumour stage. For Barcelona, the effect of better prognosis among women was most marked at local stage (HR = 0.320, P = 0.013), and in Soria at the regional stage (HR = 0.426, P = 0.002). Although in Mataró all HRs were below unity, none were statistically significant. Little effect was observed at the disseminated stage. The other covariables exerted no influence. Women appear to have a better prognosis than men, and the difference could be tumour stage dependent. Confirmation of these findings would give a valuable insight into gastric cancer growth and ultimately be of use in planning treatment.

[Eosinophilic cholecystitis associated with rupture of hepatic hydatid cyst of the bile ducts]. / Colecistitis eosinofílica asociada a ruptura de un quiste hidatídico hepático en vías biliares.

Eosinophilic cholecystitis is a rare finding characterized by an inflammatory infiltrate composed primarily of eosinophils. We report a case of eosinophilic cholecystitis associated with hepatic hydatic cyst ruptured into the biliary tract. The release of hydatid cyst content into the biliary tract may have induced a hypersensitivity reaction with numerous eosinophils in the gallbladder wall.

Organization of serotoninergic projections from the raphé nuclei to the anterior thalamic nuclei in the rat: a combined retrograde tracing and 5-HT immunohistochemical study.

We combined retrograde transport of horseradish peroxidase (HRP) with 5-hydroxytryptamine (5-HT) immunohistochemistry to study serotoninergic projections to the anterior thalamic nuclei (ATN) of the rat. Small iontophoretic injections of HRP into the anterodorsal thalamic nucleus resulted in double-labelled neurons predominantly in the ventromedial and also in the ventrolateral part of the ipsilateral dorsal raphé (DR). A smaller number of double-labelled neurons was also found in the dorsomedial part of the nucleus, predominantly ipsilaterally, and in the median raphé nucleus (MnR), close to the midline. After injection into the medial subdivision of the anteroventral thalamic nucleus, the pattern of labelling in DR and MnR was similar to that detected following injections into the anterodorsal thalamic nucleus. However, injection into the posterior subdivision of the anteroventral thalamic nucleus resulted in bilateral retrograde labelling of a few 5-HT-containing neurons in the dorsolateral part of the DR. Labelling in the ventromedial, ventrolateral and dorsomedial regions of DR and MnR was similar to that detected after injections into the medial subdivision of the anteroventral thalamic nucleus. After all injections into the ATN, double-labelled cells were found throughout the rostrocaudal extent of MnR and throughout the rostral two-thirds of DR. The caudal extension of DR was devoid of double-labelled cells. Although double-labelled cells were observed bilaterally in the dorsolateral part of the DR, the projection from DR to ATN was predominantly ipsilateral. These results show that there is an internal organization within DR such that subnuclei of the DR can be defined on the basis of their efferent projections to specific subdivisions of the ATN.

Immunohistochemical localization of GABA in the mammillary complex of the rat.

The distribution and synaptic organization of GABAergic elements in the mammillary nuclei of rats have been examined by the immunocytochemical localization of GABA at the light and electron microscope levels. The distribution of GABA-immunoreactive fibres and terminals in the mammillary body is non-homogeneous. By light microscopy, small scattered immunoreactive terminals are observed in the pars medianus, pars posterior and ventral region of the pars medialis of the medial mammillary nucleus. Larger labelled terminals are found in the pars lateralis, the dorsal region of the pars medialis of the medial mammillary nucleus and the lateral mammillary nucleus. At the ultrastructural level, GABA-immunoreactive synaptic endings in the different subdivisions of the medial mammillary nucleus exhibit a widespread somadendritic distribution. By contrast, GABA-immunoreactive terminals within the lateral mammillary nucleus are located predominantly in the neuropil and less frequently on neuronal somata. GABA-immunoreactive synaptic endings contain pleiomorphic synaptic vesicles and have symmetrical synaptic contact zones with the somata and dendrites in the lateral and medial mammillary nuclei. After in vivo inhibition of GABA metabolism with amino-oxyacetic acid, light microscopic examination of the mammillary nuclei reveals numerous small GABA-immunoreactive cells in various subdivisions of the medial mammillary nucleus. No immunoreactive cells are observed, however, in the lateral mammillary nucleus. Electron microscopic examination demonstrates that the GABA-immunoreactive cells are astrocytes. In the labelled astrocytes, immunohistochemical reaction product is localized throughout the nucleus and cytoplasm of the cells, in thin sheet-like processes surrounding neuronal elements and in end-feet lining the basal lamina of capillaries. The results indicate that the mammillary nuclei in the rat receive a strong GABAergic innervation. Most if not all, of the GABA-immunoreactive synaptic endings in the mammillary nuclei probably arise from extrinsic inhibitory sources. The possible sources of the GABA-immunoreactive input to the mammillary complex are discussed.

[Blue nevus of the prostate]. / Nevus azul de la próstata.

The presence of melanin in the prostatic gland's stroma is a histopathological finding of extreme rarity. It receives the name of blue nevus as a result of its similitude to the skin's blue nevus. The paper describes the finding of melanin stores in the fibromuscular stroma of a patient's prostate and reviews the theories on its source.