Relationship between inflammatory mediators, Aß levels and ApoE genotype in Alzheimer disease.

Activation of inflammatory processes is observed within the brain as well as periphery of subjects with Alzheimer's disease (AD). Whether or not inflammation represents a possible cause of AD or occurs as a consequence of the disease process, or, alternatively, whether the inflammatory response might be beneficial to slow the disease progression remains to be elucidated. The cytokine IL-18 shares with IL-1 the same pro-inflammatory features. Consequent to these similarities, IL-18 and its endogenous inhibitor, IL-18BP, were investigated in the plasma of AD patients versus healthy controls (HC). An imbalance of IL-18 and IL-18BP was observed in AD, with an elevated IL-18/IL-18BP ratio that might be involved in disease pathogenesis. As part of the inflammatory response, altered levels of RANTES, MCP-1 and ICAM- 1, molecules involved in cell recruitment to inflammatory sites, were observed in AD. Hence, correlations between IL-18 and other inflammatory plasma markers were analyzed. A negative correlation was observed between IL-18 and IL-18BP in both AD and HC groups. A positive correlation was observed between IL-18 and ICAM-1 in AD patients, whereas a negative correlation was evident in the HC group. IL-18 positively correlated with Aß in both groups, and no significant correlations were observed between IL-18, RANTES and MCP-1. An important piece of evidence supporting a pathophysiologic role for inflammation in AD is the number of inflammatory mediators that have been found to be differentially regulated in AD patients, and specific ones may provide utility as part of a biomarker panel to not only aid early AD diagnosis, but follow its progression.

Biological behavior due to cell proliferation markers of gastrointestinal stromal tumors.

BACKGROUND/AIMS: The mitotic index and tumor size are currently the main prognostic indicators of gastrointestinal stromal tumors (GIST). The purpose of this study is to investigate the expression of different immunohistochemical markers and their relation to mortality and relapse, and especially concerning high-risk tumors. METHODOLOGY: We did a retrospective study of 68 patients who underwent surgery from 1997 to 2007 with a diagnostic of gastrointestinal stromal tumor. RESULTS: The median follow-up period was 29 months. Relapse and mortality rates were 35.3% (24 cases) and 41.2% (28 cases), respectively. The mitotic index was related to p53 and the cellular proliferation index -Ki67- (p = 0.006 and p = 0.003, respectively). Considering both high and intermediate-risk neoplasms, a significant relation to Ki67 was obtained (p = 0.008). Relapse was related to the mitotic index (p = 0.032) and Ki67 (p = 0.024). Concerning mortality, statistically significant results were obtained with necrosis variables (p = 0.02), mitotic index (p = 0.013), p53 (p = 0.024) and Ki67 (p = 0.033). CONCLUSIONS: Ki67 could be considered a prognostic marker for both relapse and mortality. Concerning high risk GIST, the usefulness the p53 protein and Ki67 nuclear antigen markers was also evident concerning relapse and mortality.

[Quality indicators in bariatric surgery: weight loss valoration]. / Indicadores de calidad en cirugía bariátrica: Valoración de la pérdida de peso.

The medical management of MO may be effective in the short and intermediate terms, although it usually fails then leading to surgical management. Our goal is to assess Capella's surgical technique by means of quality indicators including weight loss. The present work has been performed with surgical MO patients at the 12 de Octubre University Hospital during 2000-2001, and registering the follow-up checkups for the period 2000-2001/2003-2004. We reviewed the clinical charts of 23 patients. The average Body Mass Index (BMI) was 52.24 +/- 10.07 kg/m(2), (range, 41-74.41). When compiling the statistical results, we observed statistically significant post-surgical decreases with no differences whether the PEIMCP outcome was excellent (>or= 65%), fair (= 50-65%) or failure (or= 60 kg/m(2).

Indicadores de calidad en cirugía bariátrica. Valoración de la pérdida de peso / Quality indicators in bariatric surgery. Weight loss valoration

El tratamiento médico de la OM puede resultar efectivo a corto y medio plazo, pero generalmente termina por fracasar, recurriéndose entonces al tratamiento quirúrgico. Nuestro objetivo es evaluar la técnica quirúrgica de Capella mediante unos indicadores de calidad entre los que se encuentra la valoración de la pérdida de peso. El presente estudio se ha llevado a cabo en los pacientes intervenidos quirúrgicamente de OM en el Hospital Universitario 12 de Octubre durante el bienio 2000-2001, recogiéndose los controles evolutivos del trienio 2000-2001/2003-2004. Se analizaron las historias de 23 pacientes. El Índice de Masa Corporal (IMC) medio fue de 52,24 ± 10,07 kg/m2, (rango, 41-74,41). Compendiando los resultados estadísticos se constataron descensos postoperatorios estadísticamente significativos, no percibiéndose diferencias para estas variables en función de si el resultado del PEIMCP fue excelente (≥ 65%), bueno (= 50-65%) o fracaso (≤ 50%), en los siguientes parámetros: IMC (p ≤ 0,001). Comorbilidades (p ≤ 0,001). Hemoglobinemia (p ≤ 0,005). Glucemia (p ≤ 0,001). Triglicéridemia (p ≤ 0,001). Colesterolemia Total (p ≤ 0,001). Sideremia (p ≤ 0,001). Cianocobalamina Sérica (p ≤ 0,001). Sin poder demostrarse alteraciones estadísticamente significativas en los parámetros restantes. Pero con la presunción de que la ausencia de evidencia no significa evidencia de ausencia; es decir, los resultados han sido obtenidos para un tamaño muestral pequeño (N = 23), por lo que no se pueden considerar necesariamente concluyentes. Considerando el porcentaje del exceso del índice de masa corporal perdida como uno de los índices de calidad en cirugía bariátrica, podríamos afirmar que el by-pass gástrico de Capella resulta eficiente en los pacientes obesos con un IMC ≤ 50 kg/m2, dudosamente efectivo en pacientes con un IMC comprendido entre los 50-60 kg/m2 e ineficaz en los pacientes superobesos con un IMC ≥ 60 kg/m2 (AU)

The medical management of MO may be effective in the short and intermediate terms, although it usually fails then leading to surgical management. Our goal is to assess Capella's surgical technique by means of quality indicators including weight loss. The present work has been performed with surgical MO patients at the 12 de Octubre University Hospital during 2000-2001, and registering the follow-up checkups for the period 2000-2001/2003-2004. We reviewed the clinical charts of 23 patients. The average Body Mass Index (BMI) was 52.24 ± 10.07 kg/m2, (range, 41-74.41). When compiling the statistical results, we observed statistically significant post-surgical decreases with no differences whether the PEIMCP outcome was excellent (≥ 65%), fair (= 50-65%) or failure (≤ 50%) in the following parameters: BMI (p ≤ 0.001); Comorbidities (p ≤ 0.001); Hemoglobinemia (p ≤ 0.005); Glycemia (p ≤ 0.001); Triglyceridemia (p ≤ 0.001); Total cholesterolemia (p ≤ 0.001); Sideraemia (p ≤ 0.001); and serum cianocobalamine (p ≤ 0.001). We could not demonstrate statistically significant changes in the remaining parameters. However, under the presumption that the lack of evidence does not mean the evidence of the absence, that is to say, the results have been obtained from a small sample (N = 23) so that they may not be considered definitely conclusive. Considering the percentage of the loss of Body Mass Index excess as one of the quality indexes in bariatric surgery, we may state that Capella's gastric by-pass is efficient in obese patients with BMI ≤ 50 kg/m2, doubtfully effective in patients with BMI 50-60 kg/m2, and ineffective in super obese patients with BMI ≥ 60 kg/m2 (AU)

Peripheral cytokines profile in Parkinson's disease.

Higher levels of proinflammatory cytokines are found in Parkinson's disease (PD) patient's brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of proinflammatory cytokines act on the endothelium of blood-brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this upregulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease, Br. J. Pharmacol. 50, 963-976; Kortekaas, R., Leenders, K.L., Van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176-179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha were significantly higher in PD patients than in HC subjects (p<0.001), as determined by RT-PCR and Elisa methods. Cyto/chemokine levels were significantly correlated with UPDRS III and H/Y stage (p<0.001). The Pearson's correlation coefficient (R) was also used to assess the strength of the relationship between NF-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD.

Determinación inmunohistoquímica y utilidad pronóstica del receptor del factor de crecimiento epidérmico en los tumores estromales gastrointestinales / No disponible

Introducción: el receptor del factor de crecimiento epidérmico,EGFR(HER-1), es un receptor de tirosina quinasas cuya activaciónpermite un aumento de la proliferación celular, angiogénesis,proceso metastásico y disminución de la apoptosis celular. Nuestroobjetivo es conocer el valor pronóstico de la inmunotinción deEGFR en tumores estromales gastrointestinales (GIST).Pacientes y método: estudio retrospectivo que incluye todoslos GIST intervenidos quirúrgicamente entre 1995-2007 en elServicio de Cirugía General y del Aparato Digestivo del HospitalGeneral de Ciudad Real. Variables clínicas: edad, sexo, clínica,mortalidad, recidiva. Variables patológicas: a) macroscópicas: localización,diámetro; b) microscópicas: necrosis tumoral, índicemitótico, tipo celular; y c) inmunohistoquímicas: vimentina (V9,Dako A/s); actina del músculo liso (HHF-35, Biogenex); CD34(QBEND/10); S100 (Policlonal Dako A/S); CD117 (c-kit Rabbit,antihuman polyclonal antibody, 1:600); PDGFR-alfa (Rabbitpolyclonal antibody, 1:50, Sta. Cruz Biotechnology). Variablesmoleculares pronósticas: P-53, PAb240 (DakoCytomation), 1:75,Ki-67, clona MIB1 (Dako), 1:120 y EGFR pharmDx™ Dako Autostainer(Dako, Dinamarca). Criterios de malignidad: criteriosde Fletcher.Resultados: entre 1995 y 2007, 35 GIST, fueron intervenidosquirúrgicamente en nuestro Servicio. Edad media: 61,11 ±11,02, siendo mujeres en el 62,9% de los casos. Debutaron conhemorragia digestiva en un 40%. La mediana de seguimiento fuede 28 meses (3-133). La mortalidad fue de 54,3%, con recidivadel 40%. Variables morfológicas: la localización más frecuente fuegástrica, 51,4% (18). Existió necrosis tumoral en un 57,1%, 20.El patrón celular fue fusocelular en un 57,1%, y epitelioide en un14,3%. El diámetro máximo fue de 9,58 ± 6,29. El índice mitóticopor 50 campos de gran aumento fue de 13,44 ± 16,08. En un51,45%, 18, fueron neoplasias de alto riesgo. Valores inmunohistoquímicos:CD117+, 85,7%. PDGFRA+, 85,7%. CD34+,77,1%. EGFR+, 62,9%. S100+, 34,3%. Actina+, 20%. Vimentina+,100%. p53+, 40%. ki67+, 10,71 ± 10,82. La expresión deEGFR no se relacionó con la recidiva y/o mortalidad del enfermo p = 0,156, y p = 0,332, respectivamente. El índice mitótico serelacionó con la mortalidad del enfermo, p = 0,02, y recidiva neoplásica,p = 0,013.Conclusión: en nuestra muestra no existió relación entre lainmunotinción de EGFR y el pronóstico del tumor estromal gastrointestinal

Introduction: the epidermal growth factor receptor, EGFR(HER-1), is a tyrosine kinase receptor. EGFR activation plays animportant role in increased cell proliferation, angiogenesis, anddecreased apoptosis. Our objective was to study EGFR immunoexpressionin GIST, as well as its prognostic value.Patients and method: a retrospective study that included allpatients operated on with a histologic diagnosis of GIST at Departmentof Surgery, Hospital General, Ciudad Real, between1995 and 2007. Clinical features: age, sex, manifestations, mortality,recurrence. Pathological features: origin, size, tumoralnecrosis, mitotic index, cell type. Immunohistochemical features:vimentin, (V9, Dako A/s); smooth muscle actin (HHF-35,Biogenex); CD34 (QBEND/10); S100 (Policlonal Dako A/S),CD117, (c-kit Rabbit, antihuman polyclonal antibody, 1:600);PDGFR-alfa (Rabbit polyclonal antibody, 1:50, Sta. Cruz Biotechnology).Prognostic molecular features: P-53, PAb240 (DakoCytomation)1:75; Ki-67, clona MIB1 (Dako), 1:120 y (EGFR)pharmDx™ Dako Autostainer (Dako, Denmark). Malignancycritera: Fletcher's critera.Results: from 1995 to 2007, 35 GISTs were resected in ourDepartment. Mean age: 61.11 ± 11.02, with a female predominanceof 62.9%. Initial clinical manifestation included digestivehemorrhage in 40%. Median follow-up was 28 months (3-133).Mortality was 54.3%, and recurrence rate was 40%. The mostfrequent origin was the stomach, 51.4%, (18). There was tumornecrosis in 57.1% (20). There were spindle-like cells in 57.1%,and epithelioid cells in 14.3%. Mean size was 9.58 ± 6.29. Mitoticindex per 50 high-power fields was 13.44 ± 16.08; 51.45%(18) were high-risk tumors. Immunohistochemical expression:CD117+, 85.7%. PDGFRA+, 85.7%. CD34+, 77.1%. EGFR+,62.9%. S100+, 34.3%. Actin+, 20%. Vimentin+, 100%. p53+,40%. ki67+, 10.71 ± 10.82. There was no correlation betweenEGFR expression and recurrence and/or mortality, p = 0.156and p = 0.332, respectively. Mitosis index related to mortality, p= 0.02, and recurrence, p = 0.013. Conclusion: in our study there was no relation betweenEGFR immunohistochemical expression and the prognosis of GIST (AU)

Hemorragia digestiva secundaria a lipoma duodenal / No disponible

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Íleo biliar subsecuente a una fístula colecistoduodenal (síndrome de Bouveret) / No disponible

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Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone).

Free radicals have been found in high concentrations within inflammatory multiple sclerosis (MS) lesions. The superoxide anion (O(2)(-)) reacts rapidly with nitric oxide (NO), producing peroxynitrite (ONOO(-)). Glatiramer acetate (GA) is a specific MS immunomodulator that induces the synthesis of Th2 cytokines, and reduces the frequency of relapses and the formation of active brain lesions. Proinflammatory cytokines could play a role in free radicals production in the peripheral immune system as well as in the central nervous system (CNS). The effect of GA on iNOS, superoxide radicals (O(2)(-)) and 3-nitrotyrosine production by peripheral blood adherent mononuclear cells (PBAMs) was assessed. Our findings demonstrate that in vitro GA reduced spontaneous and LPS-induced iNOS, 3-nitrotyrosine, NO and O(2)(-) production, and that similar inhibition can be demonstrated ex vivo in mononuclear cells obtained from GA-treated patients. The inhibition of the production of free radicals in PBAMs may represent a new therapeutic mechanism against inflammation during MS.

Expression and phosphorylation of protein kinase C isoforms in Abeta(1-42) activated T lymphocytes from Alzheimers disease.

The protein kinase C (PKC) family of enzymes is a regulator of transmembrane signal transduction. There is evidence demonstrating altered activity of some PKC isoforms (PKC-alpha, PKC-delta and PKC-zeta) in the neurons of brains of Alzheimers Disease (AD) sufferers, but little is known about their involvement in the intracellular machinery of amyloid beta protein-reactive T lymphocytes in AD. By applying a modified, split-well culture system, for Abeta(1-42) reactivity, we carried out flow cytometry analysis and biochemical investigations on the possible involvement of PKC-alpha, PKC-delta and PKC-zeta in the signalling system activated in Abeta-reactive T cells purified from peripheral blood mononucleate cells (PBMC) from healthy subjects and patients with AD. Flow cytometry analysis of Abeta(1-42) activated T lymphocytes in the majority of AD patients highlighted a distinct cellular cluster highly expressing phospho-PKC-delta (P-PKC-delta), while most full-blown AD patients highly expressed two distinct P-PKC-delta and phospho-PKC-zeta (P-PKC-zeta) bright sub-populations. The same investigation performed in freshly purified peripheral T lymphocytes, did not highlight any subpopulation, suggesting that the detection of P-PKC-delta and P-PKC-zeta bright subpopulations is specifically linked to Abeta(1-42) activated T lymphocytes. The data presented here, therefore, suggest possible novel hallmarks to discriminate between healthy elderly subjects and beginning or full-blown Alzheimers Disease patients.

[Immunohistochemical expression of epidermal growth factor and its prognostic value for gastrointestinal stromal tumors]. / Determinación inmunohistoquímica y utilidad pronóstica del receptor del factor de crecimiento epidérmico en los tumores estromales gastrointestinales.

INTRODUCTION: The epidermal growth factor receptor, EGFR (HER-1), is a tyrosine kinase receptor. EGFR activation plays an important role in increased cell proliferation, angiogenesis, and decreased apoptosis. Our objective was to study EGFR immuno-expression in GIST, as well as its prognostic value. PATIENTS AND METHOD: A retrospective study that included all patients operated on with a histologic diagnosis of GIST at Department of Surgery, Hospital General, Ciudad Real, between 1995 and 2007. CLINICAL FEATURES: age, sex, manifestations, mortality, recurrence. Pathological features: origin, size, tumoral necrosis, mitotic index, cell type. Immunohistochemical features: vimentin, (V9, Dako A/s); smooth muscle actin (HHF-35, Biogenex); CD34 (QBEND/10); S100 (Policlonal Dako A/S), CD117, (c-kit Rabbit, antihuman polyclonal antibody, 1:600); PDGFR-alfa (Rabbit polyclonal antibody, 1:50, Sta. Cruz Biotechnology). Prognostic molecular features: P-53, PAb240 (DakoCytomation) 1:75; Ki-67, clona MIBI (Dako, Denmark). Malignancy criteria: Fletcher's criteria. RESULTS: From 1995 to 2007, 35 GISTs were resected in our Department. Mean age: 61.11 +/- 11.02, with a female predominance of 62.9%. Initial clinical manifestation included digestive hemorrhage in 40%. Median follow-up was 28 months (3-133). Mortality was 54.3%, and recurrence rate was 40%. The most frequent origin was the stomach, 51.4%, (18). There was tumor necrosis in 57.1% (20). There were spindle-like cells in 57.1%, and epithelioid cells in 14.3%. Mean size was 9.58 +/- 6.29. Mitotic index per 50 high-power fields was 13.44 +/- 16.08; 51.45% (18) were high-risk tumors. Immunohistochemical expression: CD117+, 85.7%. PDGFRA+, 85.7%. CD34+, 77.1%. EGFR+, 62.9%. S100+, 34.3%. Actin+, 20%. Vimentin+, 100%. p53+, 40%. ki67+, 10.71 +/- 10.82. There was no correlation between EGFR expression and recurrence and/ or mortality, p = 0.156 and p = 0.332, respectively. Mitosis index related to mortality, p = 0.02, and recurrence, p = 0.013. CONCLUSION: In our study there was no relation between EGFR immunohistochemical expression and the prognosis of GIST.

Perfil molecular del cáncer colorrectal sin afectación ganglionar de mal pronóstico mediante la determinación inmunohistoquímica de p53, ki67, VEGF y metaloproteinasa 9. ¿Es útil como modelo pronóstico de recidiva? / Molecular pattern of poor prognostic colorectal cancer without nodular involvement by inmunohistochemical determination of p53, ki67, VEGF and metaloproteinase 9. It is useful as prognostic marker of recurrency?

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Masa multiquística benigna de cabeza de páncreas que simula la existencia de neoplasia quística pancreática / Benign multicystic mass in the head of pancreas simulating a pancreatic cystic neoplasia

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Compound A, formaldehyde and methanol concentrations during low-flow sevoflurane anaesthesia: comparison of three carbon dioxide absorbers.

AIM: To determine compound A, formaldehyde and methanol concentrations in low-flow anaesthesia using different carbon dioxide absorbers. METHODS: Fifteen patients scheduled for general or urological surgery were exposed to low-flow (500 ml/min) anaesthesia with sevoflurane. The patients were randomly allocated to three groups: soda lime, DrägerSorb Free or Amsorb Plus. The concentrations of compound A, formaldehyde and methanol were sampled and analysed from the limbs of the anaesthesia circuit at T30 (30 min after the start of low-flow sevoflurane anaesthesia), T90 (90 min) and T150 (150 min). The temperatures of the absorbers were measured at the same time. RESULTS: Statistically significant differences (P < 0.05) were found in the production of compound A from soda lime (with the highest values), DrägerSorb Free and Amsorb Plus at each measurement time. Only traces of methanol (ranging from < 0.131 to 3.799 mg/m(3)) were measured, higher with Amsorb Plus (statistically significant differences were found only at T90). The formaldehyde values (ranging from < 0.1227 to 17.79 mcg/m(3) p.p.b.) were higher with soda lime, and the difference was statistically significant at T150 and, in the inspiratory limb only, at T90. The temperatures of the absorbers were higher for soda lime and lower for Amsorb Plus; the difference was statistically significant at T0 in the upper canister and at T30 in both canisters. CONCLUSION: The concentrations of harmful products in the circuit were negligible and were lower using the new-generation absorbers. Using Amsorb Plus, the temperatures in the canisters were lower than with the other two absorbers.

Papilomatosis juvenil de la mama. Enfermedad del "queso suizo" / Juvenile papilomatosis of the breast

Presentamos un caso de papilomatosis juvenil de la mama, describimos la epidemiología, características clínicas y anatomopatológicas, así como los métodos diagnósticos, tipos de tratamiento y el significado pronóstico de una patología relativamente infrecuente (AU)

We present a case of juvenile papillomatosis of the breast, and describe the epidemiology, clinical and anatomopathological characteristics; also diagnostic methods, types of treatment and the prognostic significance of a relatively infrequent pathology (AU)

Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families.

Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disorder due to mutations in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13. AVED patients have progressive spinocerebellar symptoms and markedly reduced plasma levels of vitamin E. We studied neurological phenotype at diagnosis, and long-term effect of vitamin E supplementation in 16 patients from 12 Italian families. The most common mutations were the 744delA and 513insTT. Two novel TTPA mutations were identified: a severe truncating mutation (219insAT) in a homozygous patient, and a Gly246Arg missense mutation (G246R) in a compound heterozygous patient. The missense mutation was associated with a mild and slowly progressive form of the disease. Vitamin E supplementation therapy allowed a stabilization of the neurological conditions in most of the patients. However, development of spasticity and retinitis pigmentosa was noted in a few patients during therapy. Prompt genetic characterization of AVED patients may allow an effective early treatment and an adequate genetic counseling.