Changes in neuronal excitability and synaptic transmission in nucleus accumbens in a transgenic Alzheimer's disease mouse model.

Several previous studies showed that hippocampus and cortex are affected in Alzheimer's disease (AD). However, other brain regions have also been found to be affected and could contribute with new critical information to the pathophysiological basis of AD. For example, volumetric studies in humans have shown a significant atrophy of the striatum, particularly in the nucleus Accumbens (nAc). The nAc is a key component of the limbic reward system and it is involved in cognition and emotional behaviors such as pleasure, fear, aggression and motivations, all of which are affected in neurodegenerative diseases such as AD. However, its role in AD has not been extensively studied. Therefore, using an AD mouse model, we investigated if the nAc was affected in 6 months old transgenic 2xTg (APP/PS1) mice. Immunohistochemistry (IHC) analysis in 2xTg mice showed increased intraneuronal Aß accumulation, as well as occasional extracellular amyloid deposits detected through Thioflavin-S staining. Interestingly, the intracellular Aß pathology was associated to an increase in membrane excitability in dissociated medium spiny neurons (MSNs) of the nAc. IHC and western blot analyses showed a decrease in glycine receptors (GlyR) together with a reduction in the pre- and post-synaptic markers SV2 and gephyrin, respectively, which correlated with a decrease in glycinergic miniature synaptic currents in nAc brain slices. Additionally, voltage-clamp recordings in dissociated MSNs showed a decrease in AMPA- and Gly-evoked currents. Overall, these results showed intracellular Aß accumulation together with an increase in excitability and synaptic alterations in this mouse model. These findings provide new information that might help to explain changes in motivation, anhedonia, and learning in the onset of AD pathogenesis.

Role of membrane GM1 on early neuronal membrane actions of Aß during onset of Alzheimer's disease.

The ability of beta-amyloid peptide (Aß) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aß was dependent on GM1 levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aß clustering at the membrane (Aß fluorescent-punctas/20µm, control=16.2±1.1 vs. D-PDMP=6.4±0.4, p<0.001). Interestingly, membrane perforation with Aß occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control=7.8±2 vs. low GM1=12.1±0.5, p<0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aß. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control=7.8±2 vs. GM1=6.2±1min, p<0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aß with GM1 attenuated membrane perforation significantly. Furthermore, pretreatment with CTB decreased the membrane association of Aß (fluorescent-punctas/20µm, Aß: control=14.8±2.5 vs. CTB=8±1.4, p<0.05), suggesting that GM1 also plays a role in both association of Aß with the membrane and in perforation. In addition, blockade of the Aß association with CTB inhibited synaptotoxicity. Taken together, our results strongly suggest that membrane lipid composition can affect the ability of Aß to associate and subsequently perforate the plasma membrane thereby modulating its neurotoxicity in hippocampal neurons.

Prevalencia de obesidad según la estadificación de Edmonton en las consultas de Medicina Interna. Resultados del estudio OBEMI / Prevalence of obesity according to Edmonton staging in the Internal Medicine consultations. Results of the OBEMI study

Objetivos. Estimar la prevalencia de obesidad y clasificarla según la estadificación de Edmonton (EOSS) en pacientes atendidos por Medicina Interna. Material y métodos. Estudio observacional, descriptivo y transversal. Incluyó pacientes ambulatorios mayores de 18 años con un índice de masa corporal (IMC)>30, procedentes de 38 hospitales, entre el 1 y el 14 de febrero de 2016. Se clasificaron según EOSS y se analizaron variables clínicas, analíticas y sociodemográficas. Se consideró significación estadística con p<0,05. Resultados. De 1.262 pacientes vistos en las consultas se seleccionaron 298 y se analizaron 265. La prevalencia de obesidad fue del 23,6%, la edad, de 62,47±15,27 años y el IMC, de 36,1±5,3kg/m2. Por EOSS (0, 1, 2, 3 y 4) la prevalencia fue de 4,9, 14,7, 62,3, 15,5 y 2,64%, respectivamente. Aquellos pacientes con EOSS>2 tenían significativamente más edad y comorbilidades. El análisis multivariante relacionó la edad (OR 1,06, p<0,0003), la glucemia (OR 1,04, p<0,0006), el colesterol total (OR 0,98, p<0,02) y el ácido úrico (OR 1,32, p<0,02) con un EOSS>2. Un análisis de correspondencias agrupó, con un porcentaje explicativo del 78,2%, a los pacientes según su EOSS, comorbilidad, nivel de estudios, situación laboral y capacidad funcional. Conclusiones. La prevalencia de obesidad en pacientes atendidos por Medicina Interna es similar a la de la población general, aunque los pacientes son de mayor edad e IMC. El EOSS es útil para hacer una aproximación integral de los pacientes obesos, independientemente del IMC, lo que puede posibilitar la obtención de mejores resultados en salud y en calidad de vida (AU)

Objectives. To estimate the prevalence of obesity in patients treated by departments of Internal Medicine and to classify the patients according to the Edmonton Obesity Staging System (EOSS). Material and methods. An observational, descriptive cross-sectional study included outpatients older than 18 years, with a body mass index (BMI)>30, from 38 hospitals between the 1st and 14th of February, 2016. We classified the patients according to the EOSS and analysed their clinical, laboratory and demographic variables. A value of P<.05 was considered statistically significant. Results. Of the 1,262 patients treated in consultations, we recruited 298 and analysed 265. The prevalence of obesity was 23.6%, the mean age was 62.47±15.27 years, and the mean BMI was 36.1±5.3kg/m2. According to EOSS stage (0, 1, 2, 3 and 4), the prevalence was 4.9, 14.7, 62.3, 15.5 and 2.64%, respectively. Those patients with EOSS>2 were significantly older and had significantly more comorbidities. The multivariate analysis related age (OR 1.06; P<.0003), blood glucose (OR 1.04; P<.0006), total cholesterol (OR 0.98; P<.02) and uric acid (OR 1.32; P<.02) levels with an EOSS>2. An analysis of correspondence grouped, with an explanatory percentage of 78.2%, the patients according to their EOSS, comorbidity, education level, employment status and functional capacity. Conclusions. The prevalence of obesity in the patients treated by Internal Medicine departments is similar to that of the general population, although the patients are older and have a higher BMI. EOSS is useful for implementing a comprehensive approach for patients with obesity, regardless of the BMI, which can help achieve better health and quality-of-life results (AU)

Prevalence of obesity according to Edmonton staging in the Internal Medicine consultations. Results of the OBEMI study. / Prevalencia de obesidad según la estadificación de Edmonton en las consultas de Medicina Interna. Resultados del estudio OBEMI.

OBJECTIVES: To estimate the prevalence of obesity in patients treated by departments of Internal Medicine and to classify the patients according to the Edmonton Obesity Staging System (EOSS). MATERIAL AND METHODS: An observational, descriptive cross-sectional study included outpatients older than 18 years, with a body mass index (BMI)>30, from 38 hospitals between the 1st and 14th of February, 2016. We classified the patients according to the EOSS and analysed their clinical, laboratory and demographic variables. A value of P<.05 was considered statistically significant. RESULTS: Of the 1,262 patients treated in consultations, we recruited 298 and analysed 265. The prevalence of obesity was 23.6%, the mean age was 62.47±15.27 years, and the mean BMI was 36.1±5.3kg/m2. According to EOSS stage (0, 1, 2, 3 and 4), the prevalence was 4.9, 14.7, 62.3, 15.5 and 2.64%, respectively. Those patients with EOSS>2 were significantly older and had significantly more comorbidities. The multivariate analysis related age (OR 1.06; P<.0003), blood glucose (OR 1.04; P<.0006), total cholesterol (OR 0.98; P<.02) and uric acid (OR 1.32; P<.02) levels with an EOSS>2. An analysis of correspondence grouped, with an explanatory percentage of 78.2%, the patients according to their EOSS, comorbidity, education level, employment status and functional capacity. CONCLUSIONS: The prevalence of obesity in the patients treated by Internal Medicine departments is similar to that of the general population, although the patients are older and have a higher BMI. EOSS is useful for implementing a comprehensive approach for patients with obesity, regardless of the BMI, which can help achieve better health and quality-of-life results.

Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease.

Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published. Using data from the National Center for Health Statistics from 1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p<0.0001); males: 72.0 versus 74.4 yrs (p<0.0001)). Decedents with pulmonary fibrosis had a significantly greater risk of VTE. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone. These data suggest a link between a pro-fibrotic and a pro-coagulant state.

Encondroma versus condrosarcoma de bajo grado en el esqueleto apendicular. Criterios clínico-radiológicos / Enchondroma versus low grade chondrosarcoma in the appendicular skeleton: Clinical-radiological criteria

Objetivos. Determinar la validez de las características clínico-radiológicas con la biopsia y contrastar los resultados de la biopsia con el juicio clínico basado en la historia y las pruebas radiológicas. Material y método. Se incluyó a 96 pacientes con lesiones de aspecto cartilaginoso indicativas de encondroma (E) o condrosarcoma de bajo grado (CBG) según los datos clínicos y radiográficos, la anamnesis, la exploración física, la radiografía simple, la tomografía computarizada, la resonancia magnética y la gammagrafía ósea con tecnecio 99 de todo el esqueleto. Las hipótesis se constataron con el diagnóstico anatomopatológico de E o CBG. Resultados. De los 82 pacientes estudiados completamente, se consideró que 56 presentaban E (68,29%), 8 presentaban condrosarcomas (8,33%) y en 18 (18,75%) no se pudo emitir un juicio definitivo y se consideró la sospecha de CBG. En estos casos, la biopsia mostró 3 E (25%), 9 CBG (50%) y 3 no fueron definitivos, por lo que se trataron como CBG. Resultados. Por otra parte, de los 56 casos juzgados como E, se biopsiaron 15 y se diagnosticó a 5 de CBG (33,3%). Los 8 casos juzgados como CBG se biopsiaron y solo 4 biopsias (50%) confirmaron el juicio inicial. Resultados. Ninguna de las características clínico-radiológicas estudiadas mostró diferencias estadísticamente significativas que permitieran asociarlas al diagnóstico de E o CBG. Asimismo, el análisis de correlación entre el juicio emitido inicialmente y el resultado de la biopsia arrojó un valor de 0,69 (coeficiente kappa), lo que se considera una correlación buena. Conclusión. El juicio clínico-radiológico emitido a partir de la clínica y las pruebas de imagen no ha tenido validez definitiva a la hora de decidirse por simple observación o por biopsia y tratamiento en estos pacientes (AU)

Objectives. To determine the validity of the clinical-radiological characteristics with the biopsy, and contrast the biopsy results with the clinical diagnosis based on the history and radiological tests. Material and method. The study included 96 patients with cartilage type lesions suggestive of an enchondroma (E) or a low grade chondrosarcoma (LGC) according to the clinical and X-ray data, the anamnesis, physical examination, simple X-ray, computerised tomography (CT), nuclear magnetic resonance (MRI) and a Technetium-99 bone scan of the whole skeleton. The hypotheses were contrasted with the histopathological diagnosis of enchondroma or low grade chondrosarcoma. Results. Of the 82 patients studied completely, 56 were considered enchondromas (68.29%), 8 as chondrosarcomas (8.33%) and in 18 (18.75%) a definitive diagnosis could not be made and were considered as suspected LGC. Of these, the biopsy showed 3 enchondromas (25%), 9 LGC (50%) and 3 were not definitive (and were treated as LGC). Results. On the other hand, of the 56 cases diagnosed as enchondromas, 15 were biopsied, with 5 of them being diagnosed as LGC (33.3%). The 8 cases diagnosed as LGC, were also biopsied and only 4 biopsies (50%) confirmed the initial diagnosis. Results. None of the clinical-radiological characteristics study showed any statistically significant differences that would enable them to be associated with an E or a LGC. Likewise, the correlation analysis between the diagnosis issued initially and the biopsy result gave a value of 0.69 (kappa coefficient), which was considered a good correlation. Conclusion. The clinical-radiological diagnosis deduced from the clinical picture and the imaging test did not have definitive validity when deciding on simple observation or biopsy and treatment in these patients (AU)

Intraoperative ventilator settings and acute lung injury after elective surgery: a nested case control study.

BACKGROUND: While acute lung injury (ALI) is among the most serious postoperative pulmonary complications, its incidence, risk factors and outcome have not been prospectively studied. OBJECTIVE: To determine the incidence and survival of ALI associated postoperative respiratory failure and its association with intraoperative ventilator settings, specifically tidal volume. DESIGN: Prospective, nested, case control study. SETTING: Single tertiary referral centre. PATIENTS: 4420 consecutive patients without ALI undergoing high risk elective surgeries for postoperative pulmonary complications. MEASUREMENTS: Incidence of ALI, survival and 2:1 matched case control comparison of intraoperative exposures. RESULTS: 238 (5.4%) patients developed postoperative respiratory failure. Causes included ALI in 83 (35%), hydrostatic pulmonary oedema in 74 (31%), shock in 27 (11.3%), pneumonia in nine (4%), carbon dioxide retention in eight (3.4%) and miscellaneous in 37 (15%). Compared with match controls (n = 166), ALI cases had lower 60 day and 1 year survival (99% vs 73% and 92% vs 56%; p<0.001). Cases were more likely to have a history of smoking, chronic obstructive pulmonary disease and diabetes, and to be exposed to longer duration of surgery, intraoperative hypotension and larger amount of fluid and transfusions. After adjustment for non-ventilator parameters, mean first hour peak airway pressure (OR 1.07; 95% CI 1.02 to 1.15 cm H(2)O) but not tidal volume (OR 1.03; 95% CI 0.84 to 1.26 ml/kg), positive end expiratory pressure (OR 0.89; 95% CI 0.77 to 1.04 cm H(2)O) or fraction of inspired oxygen (OR 1.0; 95% CI 0.98 to 1.03) were associated with ALI. CONCLUSION: ALI is the most common cause of postoperative respiratory failure and is associated with markedly lower postoperative survival. Intraoperative tidal volume was not associated with an increased risk for early postoperative ALI.

Apoplejía pituitaria: ¿es una urgencia quirúrgica? / Pituitary apoplexy: is a surgical urgency?

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Hiperaldosteronismo e hiperparatiroidismo: ¿causalidad o casualidad? / Hyperaldosteronism and hyperparathyroidism: causality or coincidence?

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Shock anafilático inmediato tras la administración de omeprazol por vía intravenosa / Inmediate antphylactic shock after the administration of intravenous omeprazol

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Panhipopituitarismo secundario a traumatismo craneoencefálico / Panhypopytuitarism secondary to cranioencephalic trauma

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[Neurosarcoidosis mimicking cerebral tumor]. / Neurosarcoidosis simulando un tumor cerebral.

We report a case of neurosarcoidosis, which simulated a cerebral tumor located at the floor of the III ventricle, associated to an aseptic meningitis and diabetes insipidus. It was the first and only manifestation of the illness. The response to steroid therapy was very favourable, with complete clinical recuperation and radiological resolution.

Pelvic-peritoneal tuberculosis simulating ovarian carcinoma: report of three cases with elevation of the CA 125.

We report three cases of women with abdominal pathology in which an elevated serum CA 125 tumor marker could have led to an erroneous diagnosis of ovarian carcinoma. However, after peritoneal biopsies were taken, tuberculosis was diagnosed. Furthermore, specific tuberculostatic treatment normalized serum CA 125 levels.