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Langerhans cell histiocytosis (LCH) is a disease characterized by proliferation of CD1a+dendritic cells with local or diffuse organ compromise. The identification of recurrent gene mutations has confirmed the hypothesis of LCH as a true neoplasm. Lymphomatoid papulosis (LyP) belongs to the spectrum of CD30+primary cutaneous lymphomas. LCH has been described in association with other lymphoproliferative disorders. However, lesions constituted by Langerhans cells (LC) have been commonly considered reactive, related to cytokines produced by the lymphoma-microenvironment interaction. Some authors designate these lesions as "Langerhans cells-like lesions". We present the case of a 28-years-old woman with multisystem LCH and simultaneous PyL lesions with reactive LC hyperplasia.

This study was aimed at determining whether an in vivo subcutaneous exposure to n-butylparaben (n-ButP) during one complete spermatogenic cycle could be harmful to the reproductive system of young male rats. Animals were subcutaneously given 0, 150, 300 and 600 mg/kg/day of n-ButP with vehicle (peanut oil). Body and organ weights, n-ButP excretion, biochemical parameters, sperm and spermatid count, sperm motility, viability, maturity and morphology were examined. Results showed that after a completed spermatogenic cycle, although n-ButP did not induce dose-related changes in the different biochemical parameters, a significant decrease of triacylglicerides (TAG) –due to the vehicle-was found. Furthermore, no effects of n-ButP on body weight gain and relative organ weight changes were noted. Regarding sexual organs, prostate relative weight was significantly increased at the high dose of n-ButP. On the other hand, a significant increase of abnormal sperm morphology due to n-ButP exposure, accompanied by different alterations in sexual organs histopathology, was found. The current results indicate that subcutaneous exposure of n-ButP in young male rats induced toxic effects on the reproductive system, which could affect the capacity of fertilization of animals.

Chemokines, particularly chemokine (C-C- motif) ligand 2 (CCL2), control leukocyte migration into the wall of the artery and regulate the traffic of inflammatory cells. CCL2 is bound to functional receptors (CCR2), but also to atypical chemokine receptors (ACKRs), which do not induce cell migration but can modify chemokine gradients. Whether atherosclerosis alters CCL2 function by influencing the expression of these receptors remains unknown. In a necropsy study, we used immunohistochemistry to explore where and to what extent CCL2 and related receptors are present in diseased arteries that caused the death of men with coronary artery disease compared with unaffected arteries. CCL2 was marginally detected in normal arteries but was more frequently found in the intima. The expression of CCL2 and related receptors was significantly increased in diseased arteries with relative differences among the artery layers. The highest relative increases were those of CCL2 and ACKR1. CCL2 expression was associated with a significant predictive value of atherosclerosis. Findings suggest the need for further insight into receptor specificity or activity and the interplay among chemokines. CCL2-associated conventional and atypical receptors are overexpressed in atherosclerotic arteries, and these may suggest new potential therapeutic targets to locally modify the overall anti-inflammatory response.

This study was aimed at determining whether dienestrol (DIES) affects reproduction in male offspring of rats following oral maternal exposure during gestation and lactation. Pregnant rats were treated from GD 6 to PND 21. Animals received 0 (control-vehicle), 0.75, 1.5, 3.12, 6.25, 12.5, 50, 75 µg/kg bw/d of DIES. A control group -without vehicle- was also included. High DIES concentrations caused abortions at 75 and 50 µg/kg bw/d, while at 12.5 µg/kg bw/d had still miscarriages. Ten male rats per group were kept alive until PND 90 to ensure sexual maturity. Body and organ weights, anogenital distance (AGD) at PNDs 21 and 90, biochemical and sperm parameters like motility, viability, morphology, spermatozoa and resistant spermatid counts, and histopathology for sexual organs and liver were determined. An increase in organ weight (liver and sexual organs) and a decrease in AGD due to vehicle were found. A reduction of sperm motility and viability, and an increase of abnormal sperm morphology were caused by DIES, which provoked a dose-dependent prostatitis. Maternal exposure to DIES induced toxicity on the reproductive system of the male offspring, which could affect the capacity of fertilization.

Effects of oral exposure to silver nanoparticles on the sperm of rats It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200 mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters. © 2016 Elsevier Inc.

Oral subchronic exposure to silver nanoparticles in rats DOI: 10.1016/j.fct.2016.04.010 Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic exposure to polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) in adult male rats. We also assessed if oral PVP-AgNPs exposure could alter the levels of various metals (Fe, Mg, Zn and Cu) in tissues. Rats were orally given 0, 50, 100 and 200 mg/kg/day of PVP-AgNPs. Silver (Ag) accumulation in tissues, Ag excretion, biochemical and hematological parameters, metal levels, as well as histopathological changes and subcellular distribution following PVP-AgNPs exposure, were also investigated. After 90 days of treatment, AgNPs were found within hepatic and ileum cells. The major tissue concentration of Ag was found in ileum of treated animals. However, all tissues of PVP-AgNPs-exposed animals showed increased levels of Ag in comparison with those of rats in the control group. No harmful effects in liver and kidney, as well as in biochemical markers were noted at any treatment dose. In addition, no hematological or histopathological changes were found in treated animals. However, significant differences in Cu and Zn levels were found in thymus and brain of PVP-AgNPs-treated rats.

Objectives Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. Methods Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. Results HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants. Although developmental neurotoxicity of PBDEs has been already investigated, little is still known about their potential neurotoxic effects in adulthood. In this study, we assessed the oxidative damage in brain sections and the possible behavioral effects induced by exposure to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Adult male rats (10/group) received BDE-99 by gavage at single doses of 0, 0.6 or 1.2mg/kg/body weight. Forty-five days after exposure, the following behavioral tests were conducted: open-field activity, passive avoidance and Morris water maze. Moreover, cortex, hippocampus and cerebellum were processed to examine the following oxidative stress (OS) markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS). In cerebellum, BDE-99 significantly decreased SOD, CAT and GR activities at the highest BDE-99 dose. A decrease in CAT and SOD activities was also observed in cortex and hippocampus, respectively. In the behavioral tests, no BDE-99 effects were observed, while histopathological examination of the brain regions was normal. The current results show that the brain antioxidant capacity is affected by BDE-99 exposure, mainly in cerebellum. Oxidative damage could be a mechanism for BDE-99 neurotoxicity in adult rats.

The pro-oxidant activity of uranium (U) was assessed in kidney and testes of male rats, tissues in which toxic effects of this metal are well established. Eight groups of Sprague-Dawley rats received uranyl acetate dihydrate (UAD) in the drinking water at 0, 10, 20, and 40 mg/kg day for 3 months. Rats in four groups were concurrently subjected to restraint during 2 h/day throughout the study. Histopathological examination of the kidneys revealed an angiomatose transformation in U-treated animals. In kidney, thiobarbituric acid-reactive substances (TBARS) levels and oxidized glutathione (GSSG) activity were correlated with U exposure. The superoxide dismutase (SOD) activity was significantly enhanced in both kidney and testis. Oral UAD administration induced a decrease of glutathione reductase (GR) and reduced glutathione (GSH) in the male reproductive tract. The results of this study suggest that graded doses of U elicit depletion of the antioxidant defence system of the rat and induce oxidative stress in testes and kidneys. Although at the current U doses, restraint stress scarcely showed additional adverse effects, its potential influence should not be underrated.

The role of chemokine (C-C motif) ligand 2 (CCL2) in peripheral artery disease is unclear. We measured the difference between serum and plasma levels of CCL2 in patients with chronic ischemia threatening the lower extremities following the observation that atypical chemokine receptors in blood and tissue cells may prevent CCL2 from entering the circulation and consequently modulate its function of attracting monocytes to the site of lesion. To identify the influence of CCL2, we compared the patients’ values to those in bio-banked samples from a control population. Further, we explored the association with the Asp42Gly polymorphism (rs12075) in Duffy antigen chemokine receptor; one of these atypical chemokine receptors. When possible, we evaluated in surgically excised normal and affected arteries the calcium burden as well as the expression of CCL2 and related receptors reflecting the inflammatory status. Our findings indicate that circulating CCL2 was significantly associated with the severity and presence of the disease (OR 0.966, 95% CI 0.944 to 0.988, p = 0.003). Circulating CCL2 was dependent on the rs12075 genotype (AA>AG>GG), which, probably, indicates a higher expression of chemokine receptor in the arteries of AA subjects. The associations with genetic variants and the over-expression of atypical chemokine receptors in diseased arteries may have potential implications and our data indicate that CCL2 may represent a previously unrecognized factor that needs to be considered in the screening of patients with risk factors for peripheral artery disease.

Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance.Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of ≥ 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of < 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden).Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P < 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P < 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P < 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections.Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome. © 2014 Hanberger et al.; licensee BioMed Central Ltd.

Neurilemmomas are benign tumors that arise from Schwann cells. They are rarely found on bone. We describe a neurilemmoma in a 45-year-old patient that affected the distal metaphysis of the radius. Only 1 previous case has been described in the literature. We discuss the clinical presentation, the radiographic aspect, particularly the magnetic resonance imaging characteristics, and the microscopic findings.

Rodríguez-Gallego, Esther [et alt.]; 20 p.-11 fig., Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study. © 2013 Esther Rodríguez-Gallego et al., The Unitat de Recerca Biomédica is part of the Campus of International Excellence Southern Catalonia and is currently being supported by the program of consolidated groups from the Universitat Rovira i Virgili and Grants from the Fondo de Investigación Sanitaria (FIS PI08/1032, PI08/1381, and PI11/2187 PI11/00130). Esther Rodríguez-Gallego is the recipient of a Fellowship from the Generalitat de Catalunya (2012FI B 00389), Marta Riera-Borrull is the recipient of a Fellowship from the Universitat Rovira i Virgili (2010PFRURV-B2-58), and Anabel García-Heredia is the recipient of a Fellowship from Insituto de Salud Carlos III (FI12/00133).

To study the sediment yield on gypsiferous soils from semiarid degraded regions of the middle Ebro Depression, two experimental areas with different vegetation associations were selected. At La Puebla de Alfinden site the vegetation is a mixture of Helianthememun squamati and Rosmarineto-Linetum, whereas in the Mediana de Aragon it is Helianthememun squamati and Ononido tridentatae are found. This latter vegetation association is indicative of a lower degree of degradation. Two experimental plots with different vegetation cover were set up, on north and the other on a south facing's slopes. During the three year study period, the mean sediment yield was: Rosmarineto-Linetum association with a 28% vegetation cover 10.42 Tn/Ha/year; Rosmarineto-Linetum association with 70 % vegetation cover 7.53 Tn/Ha/year; Ononidetum tridentatae association with 35 % vegetation cover 1.48 Tn/Ha/year; and Ononidetum tridentatae association with 65 % vegetation cover 1.01 Tn/Ha/year. These values show that the erosion processes are controlled primarily by the vegetation association type and to a lesser extent by the vegetation cover percentage.

The reproductive toxicology of aluminum was studied in mice. Adult male mice were treated intraperitoneally with aluminum nitrate at doses of 0, 50, 100, and 200 mg/kg/day for 4 weeks before mating with untreated females. Decreased body weight was seen in all aluminum-treated groups. Decreased pregnancy rate was observed in the females mated with males previously treated with 100 or 200 mg/kg/day of aluminum nitrate. High-dose male mice showed significantly decreased testicular and epididymal weights, as well as significant decreases in testicular and spermatid counts and epididymal sperm counts. Spermatid counts were also reduced at 100 mg/kg/day. However, the sperm motility was unaffected, and the percentages of morphological normal spermatozoa in all mice exposed to aluminum were comparable to the values in control mice. Histological changes, including necrosis of spermatocytes/spermatids, were observed in the testes of male mice treated with 100 and 200 mg/kg/day of aluminum nitrate, whereas the tubular diameters were unaffected by aluminum administration. The current study demonstrates adverse effects of parenteral aluminum exposure on the mouse male reproductive system. The "no observable adverse effect level" (NOAEL) was 50 mg/kg/day.

Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs.Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters.HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P 0.001) and HDLc (r = 0.216; P = 0.005).HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

Reproduction studies were performed with gallium nitrate, an antihypercalcaemic drug that is also used as a chemotherapeutic agent for the treatment of certain malignancies. Male mice were injected subcutaneously with gallium nitrate at doses of 0 (controls), 24, 48 and 96 mg/kg/day every other day for 14 days before mating with untreated females. Fertility and reproductive performance in the gallium nitrate-treated groups did not differ significantly from controls. No significant changes were observed in the relative testes and epididymis weights. Sperm counts in the gallium nitrate-dosed groups were comparable with those in the control group, whereas the percentage of motile cells was similar between treated and untreated animals. Histopathological examination of the testes and epididymis did not reveal any changes at any dose of gallium nitrate. The no-observed-adverse effect level was 96 mg/kg body weight. This dose is about 30 times higher than the current doses of gallium nitrate administered to humans.

hemangioblastomas are benign neoplasias that are originated in the central nervous system and constitute between 1.5-2.5% of intracranial tumors. The majority of them are infratentorial, mainly affecting the cerebellum (76%). Supratentorial lessions are rare, being in these cases the frontal, parietal or temporal lobes the most common locations. Meningeal involvement is infrequent. Only eight cases have been reported in the literature. In 30% of the cases, these tumors are associated with von Hippel Lindau syndrome (VHL).67 year old woman without any medical or family history. She presented with 4 month evolution neurological symptoms. The cranial MRI scan showed a solitary solid-cystic lesion on the right paramedian frontal lobe, in contact with the falx cerebri. The pathological analysis showed a cellular proliferation composed of polygonal cells with clear cytoplasm due to the presence of intracytoplasmic vacuoles and round or oval nucleus without cytologic atypia. These cells were accompanied by a rich vascular network of capillary type and blood extravasation. She was diagnosed of supratentorial hemangioblastoma.the preoperative diagnosis of these neoplasms is difficult because the clinical suspicion is low in supratentorial location. Imaging techniques are useful but definitive diagnosis is made through pathologic examination. The use of immunohistochemical techniques is helpful for the differential diagnosis with lesions that are more common in this region. The importance of a correct diagnosis of these histologically benign tumors, lies on the possible association with VHL syndrome and its complications.

Las metastasis de neoplasias primarias de diferentes localizaciones a cabeza y cuello son un hecho infrecuente. La localizacion mas habitual de recepcion de dichas metastasis es el hueso temporal, sitio que usualmente es afectado por neoplasias que se diseminan a los huesos en general. Sin embargo, las neoplasias al conducto auditivo externo son muy raras, habiendose publicado pocos casos en la literatura . Presentamos el caso de un varon de 81 anos con clinica de dolor, acufenos y otorrea derecha. La otomicroscopia demostro una lesion polipoide en el conducto auditivo extemo derecho. La biopsia objetivo una proliferacion de celulas epiteliales atipicas que formaban luces glandulares anomalas con positividad para citoqueratina 20yantigeno carcinoembrionario. Se diagnostico como metastasis de adenocarcinoma de probable origen colonico y posteriormente se conocieron antecedentes de colectomfa 9 anos antes por adenocarcinoma de recto-sigma. Las metastasis de adenocarcinoma de colon al conducto auditivo externo son un hecho infrecuente y de aparicion tardia. Requieren un diagnostico diferencial con metastasis de adenocarcinomas de otras localizaciones y, en menor medida debido a su baja frecuencia, con tumores primarios. Entre estos ultimos, los que plantean mayores dificultades diagnosticas son los adenocarcinomas ceruminosos.

Bellini duct carcinoma or collecting duct carcinoma (CDC) is a rare but aggressive primary renal neoplasm. The coexistence of two synchronous neoplasms in the same kidney is highly infrequent. As a result, it is hardly surprising that there are no references to renal cell carcinoma (RCC) combined with CDC of the same kidney in the literature. Histology and immunohistochemistry are important tools for differentiating between the two types of tumors involved. We present the first case of a synchronous occurrence of RCC and CDC of the same kidney.

An outbreak of Trypanosoma evansi infection that occurred in mainland Spain is described. The outbreak occurred on an equine and camel farm to which dromedary camels from an infected area of the Canary Islands had recently been introduced. One of these camels developed clinical signs and T. evansi was discovered in a blood smear examination. The herd was evaluated in order to determine the extent of the disease. The results showed that 76% of the camels, 35% of the donkeys and 2% of the horses were affected. The animals were isolated and treated using Cymelarsan((R)) (0.5mg/kg). After treatment, three blood analysis using parasitological methods revealed negative results. This is the first T. evansi outbreak to have occurred in mainland Spain and the second in mainland Europe, both occurring after the introduction of dromedary camels from the Canary Islands.

Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day.

Assessment of respiratory function is the principal tool in the study of patients with lung diseases, allowing physiopathological alterations to be detected, and the severity of the process, its clinical course, and treatment response to be identified. Nowadays, assessment of respiratory function is among the investigations used by Spanish pediatricians. The Techniques Group of the Spanish Society of Pediatric Pneumology undertook the design of a protocol for the study of pulmonary function in children that would incorporate the most recent published consensus documents on basic pulmonary function assessment (spirometry and bronchodilator reversibility testing) and on airway hyperreactivity evaluation using nonspecific provocation tests. The aim of this protocol is to provide a guide to good clinical practice until new changes, based on scientific evidence, are produced.

Caspases are the main point in the apoptotic process. We have collected some information from 210 cases of Ductal breast cancer (pT1 - pT2) such as tumour size, histological differentiation degree, lymph node status and tumor necrosis in the infiltrating component and we have evaluated the number of apoptotic cells or bodies by TUNEL technique as well as immunohistochemical studies to evaluate the expression of caspase 3 and caspase 6, and proliferation index. Our results show that lymph node status and cell atypism are independent prognostic factors for recurrence and mortality and only tumour size is an independent prognostic factor for recurrence. However, the apoptotic index and the immunohistochemical expression of caspases and cell proliferation index have not turned out to be independent prognostic factors neither for recurrence nor mortality. These results show that classic prognostic factors known until now are the most important factors to predict the evolution of the illness.

Objetivos. Analizar la frecuencia y espectro de las patologías más relevantes encontradas en el estudio necrópsico. Valorar la asociación entre estancia en la Unidad de Cuidados Intensivos (UCI) inferior a 24 horas y la tasa de errores diagnósticos. Material y métodos. Estudio retrospectivo observacional durante un período de 46 meses en una UCI polivalente. Las diferencias entre el diagnóstico clínico y anatomopatológico se establecieron en función de la clasificación de Goldman. Resultados. Se realizaron 85 autopsias de un total de 520 exitus (16,3%). Cinco pacientes fueron excluidos por información incompleta. De los 80 casos, encontramos 30 pacientes con errores mayores, 21 con repercusión terapéutica y pronóstica, y 9 en los que la estrategia terapéutica no se hubiera modificado. El diagnóstico más frecuentemente encontrado en el error tipo I fue la infección bacteriana seguida de la patología cardiovascular. La tasa de errores mayores con repercusión terapéutica fue superior en los pacientes con una estancia en UCI inferior a 24 horas (40% frente a 21%; p < 0,05). Conclusiones. La autopsia continúa siendo una herramienta útil para evaluar la calidad del diagnóstico clínico. Los errores diagnósticos con repercusión terapéutica son las infecciones bacterianas y la patología cardiovascular. Los pacientes con una estancia en la UCI inferior a 24 horas presentan una tasa mayor de errores diagnósticos tipo I.

BACKGROUND The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.

In a 56-year-old Caucasian woman an ulcerated malignant mass was found at the gastric antrum in a endoscopicalstudy due to chronic anemia. The microscopical study exhibited a malignant tumor composed of two different epithelialcell types (Fig. 1), with an infiltrating growth pattern, and wide necrotic and hemorrhage areas. Nearly 60% of the tumorwas an atypical polygonal cell proliferation with intercellular bridges, keratin, and presence of pearl corns (Fig. 2), whichwas a squamous carcinoma. The rest of the tumor (40%) was an atypical glandular proliferation with back-to-back pheno-menon corresponding to an adenocarcinoma. The mitotic rate was high in both components. The tumor was perforated, sothe patient had a secondary sepsis and died a few days after surgery.Adenosquamous gastric carcinoma represents about 1% of all gastric tumors (1), with most of them occurring in Asianpatients. Only a few cases have been published in our country, and most of them in Asian patients too (2,3); thus, the inte-rest of this case is that it happened in a Caucasian patient. The origin of these tumors is controversial; the squamous com-ponent may develop from previous foci of squamous metaplasia or from the dedifferentiation of primitive cells. Electronicmicroscopical studies done in these types of tumors demonstrate that some individual cells contain both specific ultras-tructural components such as tonofibrils and mucous vacuoles (2,4).The differential diagnosis includes poor differentiated adenocarcinoma, collision tumors, pure squamous gastric carci-noma, mucoepidermoid carcinoma, and metastatic tumors. Finally, adenosquamous gastric carcinoma has a worse prog-nosis and more aggressive behavior

Apoptosis or programmed cell death produces cells breaking into several fragments of nuclei, cytoplasm or both nuclei and cytoplasm, known as apoptotic bodies which can be visualized in haematoxylin-eosin staining. Some genes (promoters and suppressors) control this process and certain mutations may induce the expression of abnormal proteins, which can be detected by immunohistochemical staining. Apoptosis can be detected by the TUNEL method either identifying apoptotic bodies or cells at the initial stages of the fragmentation process. We have studied 186 cases of infiltrating ductal breast carcinoma, stages pT1-pT2, and analysed the prognostic significance of tumour recurrence and overall survival of apoptotic index (AI) through univariate and multivariate analysis. We have also studied the immunohistochemical protein expression of apoptosis promoter and suppressors gene (p53, nuclear expression; bcl-2 and Bax, cytoplasm expression; BAG-1, nuclear and cytoplasm expression). The results indicate prognostic significance of p53 and bcl-2 related to patient death and bcl-2 and tumour size to tumour recurrence, bcl-2 acting as a protector factor (apoptotic suppressor) in both situations. On the other hand, we have not found useful prognostic information of AI either to tumour recurrence or overall survival in univariate or multivariate studies. In this study, Bax expression does not provide a new prognostic role in breast carcinoma, although it contrasts to the bcl-2 action and accelerates death.

The sixth child of non-consanguineous parents, who had suffered from severe arthrogryposis syndrome and microcephalia, died at the age of two days. Post-mortem study revealed unique morphological brain anomalies characterized by severe cerebral and cerebellar atrophy, focal cerebral mycrogiria and ectopic masses of immature cells in the periventricular region and cerebral white matter; pachygyria was absent. In addition, muscular examination was consistent with severe muscular dystrophy. These findings suggest that new forms of combined cerebral abnormalities and muscular dystrophy of congenital origin can be recognized in isolated cases.

Both inorganic mercury and uranium are known nephrotoxicants in mammals. In this study, the renal toxicity of a concurrent exposure to inorganic mercury and uranium was compared with the nephrotoxic effects of the individual metals in a rat model. Eight groups of rats, 10 animals per group, were subcutaneously given a single administration of mercuric chloride (HgCl2, 0.34 mg/kg and 0.68 mg/kg), uranyl acetate dihydrate (UAD, 2.5 mg/kg and 5 mg/kg), or combinations of both compounds at the same doses. A ninth group of rats received sc injections of 0.9% saline and was designated as the control group. Necrosis of proximal tubules, which was observed in all experimental groups, was the most relevant morphologic abnormality. Marked changes, which were remarkably greater than those induced by the individual elements, were noted in some urinary parameters in the groups concurrently exposed to HgCl2 and UAD. It could be an indicator of a synergistic interaction between mercury and uranium. In contrast, compared with the urinary levels found after individual administration of the highest doses of mercury and uranium, significant reductions in the urinary concentrations of these elements were noted following simultaneous exposure to both metals. At these doses, the reduction in the urinary metal excretion was also accompanied by significant decreases in the renal content of mercury and uranium. Whereas the results of some parameters pointed out a possible synergistic interaction between mercury and uranium, other measures hinted that an antagonistic interaction between these elements is also present.

The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results and the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate analysis show that the independent predictors related to recurrence are tumour size, lymph-node metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who presented lymph-node metastases at the time of diagnosis.

To draw pediatrician's attention to the risks of the use of designer drugs among adolescents and to review the problem.We report the case of a 15-year-old girl admitted for seizures, who rapidly developed acute liver failure and died. Clinical and pathological details are reviewed.The use of designer drugs has increased considerably amongst Spanish adolescents and has been related to deaths in young adults with a variety of symptoms. Differential diagnosis should be made with the adverse effects of recreational drugs when clinical symptoms are confusing and in any unexplained deaths. Information on the effects of designer drugs should be disseminated among the population.

operative anaesthetic care, we can obtain a better definition of the tumour mass preoperatively and accept the challenge of demanding surgical procedures. Retroperitoneal lipomata are uncommon and have an indolent presentation. Lipomas occurring in this site are a different proposition than those in other sites and require meticulous pre-operative evaluation and an exacting surgical approach if recurrence and potential malignant transformation is to be avoided.

To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p < 0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p < 0.01), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.

A case of obstructive jaundice due to extrahepatic intraductal biliary metastasis from a breast carcinoma is reported. This clinical picture was a late manifestation and the first evidence of spread of the disease. The patient was treated by surgical decompression with relief of jaundice but died 5 months later. In patients with a history of carcinoma of the breast, the possibility of extrahepatic biliary metastasis should always be considered in the differential diagnosis of jaundice. Because this condition is amenable to palliation, it is important to differentiate it from jaundice due to hepatic involvement by this tumor.

In the Ebro Basin, piping is an ubiquitous erosion process in badland areas, occurring in two main situations: on slopes of exposed Tertiary clays and in recently incised silty-clay Holocene valley-fill sediments. The quantitative importance of the main factors controlling piping processes in those conditions was obtained by statistical analysis based on multiple and stepwise regressions. Piping erosion is strongly related to a high sodium absorption ratio (SAR) which favours clay dispersion. However, the statistical analysis indicates that the chemical characteristics and the physical-chemical behaviour are a necessary condition but are not sufficient on their own to develop piping processes. On the slopes, piping is controlled by the physical and chemical properties of the material such as the dispersion index, the granulometric fraction smaller than 4 μm, pH and crack density. In the valley-fill sediments, piping is mainly controlled by the sulphate concentration in the water extract from saturated paste, which is also associated with high SAR values, and the dispersion index. In both geomorphic situations, piping is always related to high crack density and high topographic gradient., Partial financial support was provided by Projects I + D (CICYT) NAT89-1010 and LUCDEME (ICONA).

Monocytoid B-cell lymphoma, considered as a low-grade lymphoma, is seen most frequently in persons of advanced age, chiefly women. It is often diagnosed in lymph-node phase, in low stages (I-II), and peripheral blood, bone-marrow or spleen are seldom involved. The morphologic and immunohistochemical study of two patients with monocytoid B-cell lymphoma is presented. The characteristic cell morphology, with homogeneous nuclei, low number of mitoses, and clear, wide cytoplasm, was present in both. Tumour cells expressed CD45, CD20, HLA-DR and monoclonal IgM-lambda and lambda chains, respectively. Case no. 1 had more irregular nuclei, protruding nucleoli, advanced stage at diagnosis and shorter clinical course. An epithelioid granulomatous reaction was present in case no. 2, which delayed the diagnosis until relapse. The diverse forms of clinical onset of monocytoid B-cell lymphoma, as well as its possibly aggressive course, association with other types of lymphoma and the difficulties for an adequate morphologic identification are commented.