Selenium speciation studies in cancer patients to evaluate the responses of biomarkers of selenium status to different selenium compounds.

This work presents the first systematic comparison of selenium (Se) speciation in plasma from cancer patients treated orally with three Se compounds (sodium selenite, SS; L-selenomethionine, SeMet; or Se-methylselenocysteine, MSC) at 400 µg/day for 28 days. The primary goal was to investigate how these chemical forms of Se affect the plasma Se distribution, aiming to identify the most effective Se compound for optimal selenoprotein expression. This was achieved using methodology based on HPLC-ICP-MS after sample preparation/fractionation approaches. Measurements of total Se in plasma samples collected before and after 4 weeks of treatment showed that median total Se levels increased significantly from 89.6 to 126.4 µg kg-1 Se (p < 0.001), particularly when SeMet was administered (190.4 µg kg-1 Se). Speciation studies showed that the most critical differences between treated and baseline samples were seen for selenoprotein P (SELENOP) and selenoalbumin after administration with MSC (p = 5.8 × 10-4) and SeMet (p = 6.8 × 10-5), respectively. Notably, selenosugar-1 was detected in all low-molecular-weight plasma fractions following treatment, particularly with MSC. Two different chromatographic approaches and spiking experiments demonstrated that about 45% of that increase in SELENOP levels (to ~ 8.8 mg L-1) with SeMet is likely due to the non-specific incorporation of SeMet into the SELENOP affinity fraction. To the authors' knowledge, this has not been reported to date. Therefore, SELENOP is probably part of both the regulated (55%) and non-regulated (45%) Se pools after SeMet administration, whereas SS and MSC mainly contribute to the regulated one.

Accumulation of molybdenum in major organs following repeated oral administration of bis-choline tetrathiomolybdate in the Sprague Dawley rat.

Molybdenum is an essential dietary trace element required for several critical enzyme systems. High intake is associated with toxicity in ruminants and animal studies. The proposed therapeutic use of molybdenum-based drugs poses a potential risk for accumulation through chronic administration of therapeutic doses of this element. The current experiment was designed to study the effect of daily dosing of a molybdenum compound, bis-choline tetrathiomolybdate (TTM), in Sprague Dawley rats using laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-ToF-MS) and two dosing levels of TTM for up to 3 months. To investigate if molybdenum accumulation was associated with tissue toxicity, histopathology, haematology and clinical biochemistry markers of toxicity were incorporated into the study design. There were no behavioural signs of toxicity to the rats, and no clinical or anatomic pathology was associated with treatment. The current data did show a progressive accumulation of molybdenum within the adrenal gland, kidneys, liver, spleen, brain and testes. Although this was not associated with tissue toxicity within the 3-month study design, greater exposure over a longer period of time has the potential for producing adverse pathophysiological cellular function. Tissue toxicity, as a result of local excessive accumulation of molybdenum over time, has clear implications for the therapeutic use of molybdenum in humans and demands sensitive monitoring of tissue molybdenum levels to avoid toxicity. The current study highlights the shortcomings of conventional biomonitoring approaches to detect molybdenum accumulation with the goal of avoiding molybdenum-associated toxicity.

Simulation of thermal sanitization of air with heat recovery as applied to airborne pathogen deactivation.

The technique of air sterilization by thermal effect was revisited in this work. The impact of incorporating a high efficiency heat recovery exchanger to a sterilizing cell was especially assessed. A mathematical model was developed to study the dynamics and the steady state of the sterilizer. Computer simulation and reported data of thermal inactivation of pathogens permitted obtaining results for a proof-of-concept. The simulation results confirmed that the incorporation of a heat recovery exchanger permits saving more than 90% of the energy needed to heat the air to the temperature necessary for sterilization, i.e., sterilization without heat recovery consumes 10-20 times the energy of the same sterilization device with heat recovery. Sanitization temperature is the main process variable for sanitization, a fact related to the activated nature of the thermal inactivation of viruses and bacteria. Heat recovery efficiency was a strong function of the heat transfer parameters but also rather insensitive to the cell temperature. The heat transfer area determined the maximum capacity of the sterilizer (maximum air flowrate) given the restrictions of minimum sanitization efficiency and maximum power consumption. The proposed thermal sterilization device has important advantages of robustness and simplicity over other commercial sterilization devices, needing practically no maintenance and eliminating a big variety of microorganisms to any desired degree. For most pathogens, the inactivation can be total. This result is not affected by the uncertainties in thermal inactivation data, due to the Arrhenius-like dependence of inactivation. Temperature can be adjusted to achieve any removal degree.

A fit-for-purpose copper speciation method for the determination of exchangeable copper relevant to Wilson's disease.

Exchangeable copper (CuEXC), mainly comprised copper (Cu) bound to albumin, has been proposed as a specific marker of Cu overload in Wilson's disease (WD). To the author's knowledge, there are no methods capable of determining reliably CuEXC to meet the requirements and challenges faced by a clinical trial. The present work describes a novel speciation strategy for the determination of the main Cu-species in human serum by anion-exchange high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). A label-free protein quantification approach was conducted where the concentration of Cu associated to the protein fraction was based on its relative peak area distribution and the total Cu concentration in the sample. Such a methodology was characterized in terms of selectivity, sensitivity, precision, and robustness. Due to the lack of speciated Cu-reference materials, protein recovery was assessed by comparison with that of species-specific (SS) isotope dilution (ID). For this, a double SS HPLC-ICP-IDMS method for Cu-albumin was developed and presented here for the first time. Three human sera (two frozen LGC8211 and ERM®-DA250a, and the lyophilised Seronorm™ Human) were analyzed using both the relative and ID quantification methods. The validated relative approach, with relative expanded uncertainties (k = 2) between 5.7 and 10.1% for Cu-albumin concentrations ranging from 112 to 455 µg kg-1 Cu, was found to be able to discriminate between healthy and WD populations in terms of Cu-albumin content. Also, using such methodology, underestimation of CuEXC by the classical EDTA/ultrafiltration method was demonstrated. The methodology developed in this work will be invaluable for quality control assessment and WD drug monitoring. This work describes a Cu-protein quantification approach for the determination of exchangeable Cu relevant to Wilson's Disease.

Assessment of changes in autophagic vesicles in human immune cell lines exposed to nano particles.

BACKGROUND: Safe and rational development of nanomaterials for clinical translation requires the assessment of potential biocompatibility. Autophagy, a critical homeostatic pathway intrinsically linked to cellular health and inflammation, has been shown to be affected by nanomaterials. It is, therefore, important to be able to assess possible interactions of nanomaterials with autophagic processes. RESULTS: CEM (T cell), Raji (B lymphocyte), and THP-1 (human monocyte) cell lines were subject to treatment with rapamycin and chloroquine, known to affect the autophagic process, in order to evaluate cell line-specific responses. Flow cytometric quantification of a fluorescent autophagic vacuole stain showed that maximum observable effects (105%, 446%, and 149% of negative controls) were achieved at different exposure durations (8, 6, and 24 h for CEM, Raji, and THP-1, respectively). THP-1 was subsequently utilised as a model to assess the autophagic impact of a small library of nanomaterials. Association was observed between hydrodynamic size and autophagic impact (r2 = 0.11, p = 0.004). An ELISA for p62 confirmed the greatest impact by 10 nm silver nanoparticles, abolishing p62, with 50 nm silica and 180 nm polystyrene also lowering p62 to a significant degree (50%, 74%, and 55%, respectively, p < 0.05). CONCLUSIONS: This data further supports the potential for a variety of nanomaterials to interfere with autophagic processes which, in turn, may result in altered cellular function and viability. The association of particle size with impact on autophagy now warrants further investigation.

Demethylation of Methylmercury in Bird, Fish, and Earthworm.

Toxicity of methylmercury (MeHg) to wildlife and humans results from its binding to cysteine residues of proteins, forming MeHg-cysteinate (MeHgCys) complexes that hinder biological functions. MeHgCys complexes can be detoxified in vivo, yet how this occurs is unknown. We report that MeHgCys complexes are transformed into selenocysteinate [Hg(Sec)4] complexes in multiple animals from two phyla (a waterbird, freshwater fish, and earthworms) sampled in different geographical areas and contaminated by different Hg sources. In addition, high energy-resolution X-ray absorption spectroscopy (HR-XANES) and chromatography-inductively coupled plasma mass spectrometry of the waterbird liver support the binding of Hg(Sec)4 to selenoprotein P and biomineralization of Hg(Sec)4 to chemically inert nanoparticulate mercury selenide (HgSe). The results provide a foundation for understanding mercury detoxification in higher organisms and suggest that the identified MeHgCys to Hg(Sec)4 demethylation pathway is common in nature.

Chemical Proteomics Uncovers EPHA2 as a Mechanism of Acquired Resistance to Small Molecule EGFR Kinase Inhibition.

Tyrosine kinase inhibitors (TKIs) have become an important therapeutic option for treating several forms of cancer. Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR), is in clinical use for treating non-small cell lung cancer (NSCLC) harboring activating EGFR mutations. However, despite high initial response rates, many patients develop resistance to gefitinib. The molecular mechanisms of TKI resistance often remain unclear. Here, we describe a chemical proteomic approach comprising kinase affinity purification (kinobeads) and quantitative mass spectrometry for the identification of kinase inhibitor resistance mechanisms in cancer cells. We identified the previously described amplification of MET and found EPHA2 to be more than 10-fold overexpressed (p < 0.001) in gefitinib-resistant HCC827 cells suggesting a potential role in developing resistance. siRNA-mediated EPHA2 knock-down or treating cells with the multikinase inhibitor dasatinib restored sensitivity to gefitinib. Of all dasatinib targets, EPHA2 exhibited the most drastic effect (p < 0.001). In addition, EPHA2 knockdown or ephrin-A1 treatment of resistant cells decreased FAK phosphorylation and cell migration. These findings confirm EPHA2 as an actionable drug target, provide a rational basis for drug combination approaches, and indicate that chemical proteomics is broadly applicable for the discovery of kinase inhibitor resistance.

Estimación semiautomática de la densidad mamaria con DM-Scan / Semiautomatic estimation of breast density with DM-Scan software

Objetivo. Evaluar la reproducibilidad del cálculo de la densidad mamaria con la aplicación informática DM-Scan, basada en la segmentación semiautomática del tejido fibroglandular, y compararla con la de la inspección visual. Material y métodos. El estudio incluyó 655 mamografías digitales directas en proyección cráneo-caudal. Tres expertos radiólogos analizaron la densidad de las mamografías con DM-Scan, y se calcularon las concordancias inter e intraobservador entre pares de radiólogos para las escalas Boyd y BI-RADS®, utilizando el índice de correlación intraclase. Las concordancias se compararon con las obtenidas previamente para la inspección visual, en el mismo conjunto de imágenes, utilizando el índice Kappa. Resultados. Con el análisis visual, la concordancia media interobservador fue de 0,876 (IC 95%: 0,873-0,879) para la escala de Boyd, y 0,823 (IC 95%: 0,818-0,829) para la clasificación BI-RADS®. La concordancia intraobservador fue de 0,813 (IC 95%: 0,796-0,829) para la escala de Boyd, y 0,770 (IC 95%: 0,742-0,797) para la clasificación BI-RADS®. Con DM-Scan, la concordancia media inter e intraobservador fue de 0,92, notablemente superior a las concordancias de la clasificación visual. Conclusión. El cálculo de la densidad mamaria con la aplicación semiautomática DM-Scan es más fiable y reproducible, y disminuye la subjetividad y variabilidad de la estimación visual (AU)

Objective. To evaluate the reproducibility of the calculation of breast density with DM-Scan software, which is based on the semiautomatic segmentation of fibroglandular tissue, and to compare it with the reproducibility of estimation by visual inspection. Material and methods. The study included 655 direct digital mammograms acquired using craniocaudal projections. Three experienced radiologists analyzed the density of the mammograms using DM-Scan, and the inter- and intra-observer agreement between pairs of radiologists for the Boyd and BI-RADS® scales were calculated using the intraclass correlation coefficient. The Kappa index was used to compare the inter- and intra-observer agreements with those obtained previously for visual inspection in the same set of images. Results. For visual inspection, the mean interobserver agreement was 0,876 (95% CI: 0,873-0,879) on the Boyd scale and 0,823 (95% CI: 0,818-0,829) on the BI-RADS® scale. The mean intraobserver agreement was 0,813 (95% CI: 0,796-0,829) on the Boyd scale and 0,770 (95% CI: 0,742-0,797) on the BI-RADS® scale. For DM-Scan, the mean inter- and intra-observer agreement was 0,92, considerably higher than the agreement for visual inspection. Conclusion. The semiautomatic calculation of breast density using DM-Scan software is more reliable and reproducible than visual estimation and reduces the subjectivity and variability in determining breast density (AU)

Radiología del carcinoma renal / Imaging renal cell carcinoma

El carcinoma de células renales es la octava neoplasia maligna más frecuente en el adulto y la más frecuente del riñón. Es, por tanto, una enfermedad muy común para el radiólogo. El objetivo de esta revisión es hacer una aproximación general a las diferentes técnicas de imagen utilizadas para diagnosticar, caracterizar y ayudar a planificar el tratamiento del carcinoma de células renales, así como hacer consideraciones básicas sobre la estadificación, el tratamiento percutáneo guiado con técnicas de imagen y el seguimiento en las situaciones clínicas más habituales (AU)

Renal cell carcinoma is the eighth most common malignancy in adults and the most common malignancy in the kidney. It is thus a very common disease for radiologists. This review aims to provide a general overview of the imaging techniques used to diagnose, characterize, and help plan the treatment of renal cell carcinoma as well as to review basic aspects related to staging, imaging-guided percutaneous treatment, and follow-up in the most common clinical scenarios (AU)

Semiautomatic estimation of breast density with DM-Scan software.

OBJECTIVE: To evaluate the reproducibility of the calculation of breast density with DM-Scan software, which is based on the semiautomatic segmentation of fibroglandular tissue, and to compare it with the reproducibility of estimation by visual inspection. MATERIAL AND METHODS: The study included 655 direct digital mammograms acquired using craniocaudal projections. Three experienced radiologists analyzed the density of the mammograms using DM-Scan, and the inter- and intra-observer agreement between pairs of radiologists for the Boyd and BI-RADS® scales were calculated using the intraclass correlation coefficient. The Kappa index was used to compare the inter- and intra-observer agreements with those obtained previously for visual inspection in the same set of images. RESULTS: For visual inspection, the mean interobserver agreement was 0,876 (95% CI: 0,873-0,879) on the Boyd scale and 0,823 (95% CI: 0,818-0,829) on the BI-RADS® scale. The mean intraobserver agreement was 0,813 (95% CI: 0,796-0,829) on the Boyd scale and 0,770 (95% CI: 0,742-0,797) on the BI-RADS® scale. For DM-Scan, the mean inter- and intra-observer agreement was 0,92, considerably higher than the agreement for visual inspection. CONCLUSION: The semiautomatic calculation of breast density using DM-Scan software is more reliable and reproducible than visual estimation and reduces the subjectivity and variability in determining breast density.

[Imaging renal cell carcinoma]. / Radiología del carcinoma renal.

Renal cell carcinoma is the eighth most common malignancy in adults and the most common malignancy in the kidney. It is thus a very common disease for radiologists. This review aims to provide a general overview of the imaging techniques used to diagnose, characterize, and help plan the treatment of renal cell carcinoma as well as to review basic aspects related to staging, imaging-guided percutaneous treatment, and follow-up in the most common clinical scenarios.

Diophantine analysis complements electrospray-Q-TOF data for structure elucidation of transferrin glycoforms used for clinical diagnosis in human serum and cerebrospinal fluid.

The use of ESI-Q-TOF in combination with theoretical mapping of possible glycan variants by Diophantine mass analysis allows identification of transferrin (Tf) glycoforms in different biological fluids including human serum and cerebrospinal fluid (CSF). In order to restrict the structural variations, a chromatographic separation (HPLC) of the forms with different number of sialic acids is initially conducted. The individual fractions are purified, preconcentrated, and analyzed by ESI-Q-TOF. The results obtained experimentally are compared with those predicted by Diophantine calculations and the structures proposed. Each one of the found masses can be ascribed to a single Tf glycoform with a mass difference that ranged between -1 and -26 Da (average masses). Thus, the methodology can be used for structural characterization of Tf glycoforms relevant for clinical diagnosis without enzymatic digestion.

The potential of mass spectrometry to study iron-containing proteins used in clinical diagnosis.

Many proteins contain iron as metal ion either within their own structures or bound to their active sites. These iron-containing proteins are involved in numerous biological processes and some of them serve as biomarkers of clinical pathologies, not only related to iron homeostasis but also to other physiological disorders. Thus, a variety of analytical strategies have been developed over the last years in order to conduct studies on Fe-containing proteins. Among them, mass spectrometric (MS) methods still remain as preferred tools since they provide the capabilities of structure elucidation together with quantitative possibilities. Therefore, in this work we have tried to summarize the most recent applications of elemental and molecular mass spectrometric-based methods for the characterization (mostly qualitative but quantitative in some cases) of the high abundant Fe-containing proteins used for clinical diagnosis.

Stable isotope labelling and FPLC-ICP-SFMS for the accurate determination of clinical iron status parameters in human serum.

Iron is involved in the function of all living cells and, in fact, many diseases arise from imbalances in iron homeostasis. Therefore, the development of analytical methodologies to improve and automate the measurement of clinical indices of iron status has increased tremendously over the years. This work describes the development of two complementary methodologies to evaluate transferrin (Tf) saturation, total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC) and serum iron based on the use of iron-selective monitoring by inductively coupled plasma mass spectrometry (ICP-MS). The first methodology is based on the saturation of transferrin (Tf) with natural Fe3+ followed by separation of the different sialoforms in an anion exchange column (Mono-Q) to quantify the iron in each Tf sialoform and total Tf by ICP-MS using post-column isotope dilution analysis. In the second part, the saturation is done with an iron tracer (57Fe) and the application of pattern deconvolution analysis permits the direct quantification of the Tf saturation, the serum iron and the unsaturated iron-binding capacity. These strategies are validated by using a reference serum certified for total Tf and tested also in serum samples from individuals suffering from hemochromatosis and Fe-supplemented patients. The results obtained for all the parameters related to Fe status were in good agreement with those obtained by clinical tests. The use of stable isotope labelling in connection with the on-line coupling of fast protein liquid chromatography (FPLC) to ICP-MS allows the accurate determination of several parameters of great clinical relevance in iron homeostasis by means of two independent chromatographic runs. The main advantage of the proposed methodology is the number of parameters that can be simultaneously obtained.

Accurate determination of human serum transferrin isoforms: Exploring metal-specific isotope dilution analysis as a quantitative proteomic tool.

Carbohydrate-deficient transferrin (CDT) measurements are considered a reliable marker for chronic alcohol consumption, and its use is becoming extensive in forensic medicine. However, CDT is not a single molecular entity but refers to a group of sialic acid-deficient transferrin isoforms from mono- to trisialotransferrin. Thus, the development of methods to analyze accurately and precisely individual transferrin isoforms in biological fluids such as serum is of increasing importance. The present work illustrates the use of ICPMS isotope dilution analysis for the quantification of transferrin isoforms once saturated with iron and separated by anion exchange chromatography (Mono Q 5/50) using a mobile phase consisting of a gradient of ammonium acetate (0-250 mM) in 25 mM Tris-acetic acid (pH 6.5). Species-specific and species-unspecific spikes have been explored. In the first part of the study, the use of postcolumn addition of a solution of 200 ng mL(-1) isotopically enriched iron (57Fe, 95%) in 25 mM sodium citrate/citric acid (pH 4) permitted the quantification of individual sialoforms of transferrin (from S2 to S5) in human serum samples of healthy individuals as well as alcoholic patients. Second, the species-specific spike method was performed by synthesizing an isotopically enriched standard of saturated transferrin (saturated with 57Fe). The characterization of the spike was performed by postcolumn reverse isotope dilution analysis (this is, by postcolumn addition of a solution of 200 ng mL(-1) natural iron in sodium citrate/citric acid of pH 4). Also, the stability of the transferrin spike was tested during one week with negligible species transformation. Finally, the enriched transferrin was used to quantify the individual isoforms in the same serum samples obtaining results comparative to those of postcolumn isotope dilution and to those previously published in the literature, demonstrating the suitability of both strategies for quantitative transferrin isoform determination in real samples.

Quantification and characterization of carotid calcium with multi-detector CT-angiography.

OBJECTIVE: The aim of this study was to assess the accuracy of CT-angiography for identification and measurement of calcification of carotid atherosclerotic plaques and to characterise the content and distribution pattern of mineral calcium (hydroxyapatite, Ca) in carotid bifurcations and investigate its relationship with neurological symptoms. METHODS: Twenty-six patients with ICA stenosis > 60% (13 symptomatic, 13 asymptomatic) were selected for study. Ca was estimated from the weight of the ashed remnants of carotid endarterectomy (CEA) specimens in 11 patients. Calcium content (calcification volume (mm3),CV), and average calcium density (Hounsfield units (HU),CD), were determined by CT-angiography. The distribution pattern of calcium within the lesion (base (posterior), shoulder or luminal surface) was assessed in all cases. RESULTS: CT-derived estimation of CV and Ca mass (modified Agatston Score, (mAS) = CV x CD) showed a good correlation with its direct measurement in CEA specimens (r = 0.911 and 0.993 respectively, p < 0,005). Asymptomatic patients with ICA stenosis > 60% showed statistically significant higher content of Ca than those who were symptomatic (mAS: 122.6 +/- 138.0 HU mm3 vs 42.8 +/- 59.1 HU mm3, p = 0.04). Calcification on the surface of the plaque was observed more commonly in asymptomatic patients (9/12 vs 3/15, p = 0.006). Non-calcified or plaques with posterior calcification were 12 times more likely to be symptomatic (OR: 12, 95%CI 1.5-91.1, p = 0.021). CONCLUSIONS: CT-angiography permits the reliable quantification of calcification of carotid plaques. A lower content of calcium in carotid plaques, as well as its distribution in the base of the lesion, was associated with a greater prevalence of neurological symptoms. These parameters may be useful to identify those patients at higher risk of stroke.

Preparation and properties of an immobilized pectinlyase for the treatment of fruit juices.

Pectinlyase, present in different commercial pectinases used in juice technology, was immobilized on alginate beads. The optimal conditions were: 0.17 g alginate ml(-1), 1.2% (w/v or v/v) enzyme concentration and acetic-HCl/glycine-HCl buffer at pH 3.6 or tris-HCl/imidazole buffer at pH 6.4. Maximum percentage of immobilization (10.6%) was obtained with Rapidase C80. Kinetic parameters of free and immobilized pectinlyase were also determined. The pH and temperature at which activity of soluble and immobilized enzyme was maximum were 7.2 and 55 degrees C. Thermal stability was not significantly altered by immobilization, especially at 40 degrees C, showing two periods of different stability. Free and immobilized preparation reduced the viscosity of highly esterified pectin from 1.09 to 0.70 and 0.72 mm(2) s(-1), respectively, after 30 min at 40 degrees C. Furthermore, the immobilized enzyme could be re-used through 4 cycles and the efficiency loss in viscosity reduction was found to be only 9.2%.

Strategies to study human serum transferrin isoforms using integrated liquid chromatography ICPMS, MALDI-TOF, and ESI-Q-TOF detection: application to chronic alcohol abuse.

Variations in the distribution of sialoforms of human serum transferrin (Tf) in correlation with pathological states, which are associated with abnormalities in glycosylation, is of great clinical interest. In such studies, the methodologies of analysis are required to be sensitive and selective for observing small variations among isoforms and able to characterize the molecular structure of such forms. Thus, the present work describes, in the first part, the separation of transferrin isoforms, after iron saturation of the protein, by high-performance liquid chromatography (HPLC) and the on-line specific atomic detection of the iron present on each of the separated isoforms by on-line coupling the HPLC system to an inductively coupled plasma mass spectrometer (ICPMS). This allowed low detection levels for the different isoforms (L.D. 0.03 microMTf). After screening of the isoforms containing iron by ICPMS, structural characterization of each isoform can be independently carried out. Thus, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF) and electrospray mass spectrometry (ESI-Q-TOF) are compared in the second part of this study. The different atomic and molecular MS methods revealed the presence of elevated carbohydrate-deficient transferrin (CDT) isoforms in human serum samples from chronic alcohol consumption patients. MALDI-TOF appeared to be sensitive to concentration levels of the analytes, and the observed mass accuracy was highly compromised by the protein heterogeneity (peak width at half-maximum approximately 2000 Da for every fraction). On the other hand, ESI-Q-TOF allowed good mass accuracy (m < or = 0.05%) and peak width of 45 Da in the deconvoluted spectra; while ICPMS detection could be preferable for sensitive protein isoforms determinations, ESI-Q-TOF turns out to be an excellent "fingerprinting" technique for alcoholism diagnosis.

Vacunación antigripal en promoción de la salud de un colectivo de empleados postales / Influenza vaccination in health promotion to one population of postal workers

En este estudio se ha descrito el modelo de distribución del brote epidémico por influenza, correspondiente al 2001, en una población de 5.801 empleados postales. En dicha distribución se encontraron mayores niveles de exposición a la infección en los empleados de menor edad, así como en las mujeres, con respecto a la población general, que cabe atribuir a su menor nivel de vacunación. Asimismo, se encontraron mayores niveles de exposición en el colectivo de los empleados expuestos a trabajos penosos y a intemperie, que cabe atribuir a estas condiciones de trabajo. Por último, la mayor incidencia de la influenza en este período con respecto al de 2000 cabe interpretarla en función de las menores temperaturas en este período. La menor reincidencia en el brote de 2001, con respecto al de 2000, podría explicarse por la existencia de una única onda en el 2001, cuando en el 2002 hubieron dos. Concluye el estudio recomendando la vacunación en los colectivos de riesgo, ancianos, inmunodeprimidos y enfermos crónicos, así como en los cuidadores de estos, y en los trabajadores en puestos de mayor susceptibilidad, como en trabajos penosos e intemperie (AU)

Agreement between CSF flow dynamics in MRI and ICP monitoring in the diagnosis of normal pressure hydrocephalus. Sensitivity and specificity of CSF dynamics to predict outcome.

OBJECTIVES: The aims of the study were 1) to assess the degree of agreement between CSF flow dynamics determined by MR and ICP monitoring in the diagnosis of NPH, and 2) to determine the sensitivity and specificity of CSF flow dynamics studied by MR in predicting improvement after shunting. PATIENTS AND METHODS: A prospective study was carried out in 35 consecutive patients with suspected NPH. CSF velocity (Phase Contrast) through the aqueduct was determined in sagittal plane. Patients were classified as "normal" or hyperdynamic in comparison with a control group of 27 healthy volunteers. Continuous extradural ICP monitoring was performed for at least 72 hours and patients were classified as having active, compensated, or ex-vacuo hydrocephalus. Patients with active or compensated hydrocephalus were shunted. RESULTS: The degree of agreement between MR dynamics and ICP monitoring was 82%. Sensitivity of CSF velocity was 90% and specificity was 50%. CONCLUSIONS: The degree of agreement between ICP monitoring and CSF velocity is high. High CSF velocity through the aqueduct is a good predictor of improvement after surgery. However, patients with normal velocity in MR required additional tests before a diagnosis of NPH is ruled out.