Diagnostic reference levels and complexity indices in interventional radiology: a national programme.

OBJECTIVES: To propose national diagnostic reference levels (DRLs) for interventional radiology and to evaluate the impact of the procedural complexity on patient doses. METHODS: Eight interventional radiology units from Spanish hospitals were involved in this project. The participants agreed to undergo common quality control procedures for X-ray systems. Kerma area product (KAP) was collected from a sample of 1,649 procedures. A consensus document established the criteria to evaluate the complexity of seven types of procedures. DRLs were set as the 3rd quartile of KAP values. RESULTS: The KAP (3rd quartile) in Gy cm2 for the procedures included in the survey were: lower extremity arteriography (n = 784) 78; renal arteriography (n = 37) 107; transjugular hepatic biopsies (THB) (n = 30) 45; biliary drainage (BD) (n = 314) 30; uterine fibroid embolization (UFE) (n = 56) 214; colon endoprostheses (CE) (n = 31) 169; hepatic chemoembolization (HC) (n = 269) 303; femoropopliteal revascularization (FR) (n = 62) 119; and iliac stent (n = 66) 170. The complexity involved the increases in the following KAP factors from simple to complex procedures: THB x4; BD x13; UFE x3; CE x3; HC x5; FR x5 and IS x4. CONCLUSIONS: The evaluation of the procedure complexity in patient doses will allow the proper use of DRLs for the optimization of interventional radiology. KEY POINTS: • National DRLs for interventional procedures have been proposed given level of complexity • For clinical audits, the level of complexity should be taken into account. • An evaluation of the complexity levels of the procedure should be made.

Screening antimutagenic and antiproliferative properties of extracts isolated from Jackfruit pulp (Artocarpus heterophyllus Lam).

The present focused on the study of the antimutagenic and antiproliferative potential of pulp Jackfruit (Artocarpus heterophyllus Lam) extract, using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line M12.C3.F6 (murine B-cell lymphoma), respectively. Jackfruit pulp extract was sequentially fractionated by chromatography (RP-HPLC) and each fraction was tested for antimutagenic and antiproliferative activities. The organic extracts obtained from Jackfruit pulp reduced the number of revertants caused by aflatoxin B1 (AFB1) and proliferation of cells M12.C3.F6; a dose-response relationship was showed. Sequential RP-HPLC fractionation of the active extracts produced both antimutagenic and/or antiproliferative fractions. These results suggested that the Jackfruit contained compounds with chemoprotective properties to reduce the mutagenicity of AFB1, also proliferation of a cancer cell line.

A universal dose-response curve for radiochromic films.

PURPOSE: This paper presents a model for dose-response curves of radiochromic films. It is based on a modified version of single-hit model to take into account the growth experienced by lithium salt of pentacosa-10,12-diynoic acid polymers after irradiation. METHODS: Polymer growth in radiochromic films is a critical phenomenon that can be properly described by means of percolation theory to provide an appropriate distribution function for polymer sizes. Resulting functional form is a power function featuring a critical exponent and two adjustable parameters. Moreover, these parameters act as scaling factors setting a natural scale for sensitometric curves where the dependence on channel sensitivity is removed. A unique reduced response curve is then obtained from all the color channels describing film behavior independently of film dosimetry system. RESULTS: Resulting functional form has been successfully tested in several sensitometric curves from different Gafchromic EBT models, providing excellent agreement with experimental data in a wide dose range up to about 40 Gy and low dose uncertainty. CONCLUSIONS: The model presented in this paper describes accurately the sensitometric curves of radiochromic films in wide dose ranges covering all typical ranges used in external radiotherapy. Resulting dose uncertainty is low enough to render a reasonably good performance in clinical applications. Due to cross-correlation, only one of the adjustable parameters is totally independent and characterizes film batches.

p27Kip1 represses transcription by direct interaction with p130/E2F4 at the promoters of target genes.

The cyclin-cdk (cyclin-dependent kinase) inhibitor p27Kip1 (p27) has a crucial negative role on cell cycle progression. In addition to its classical role as a cyclin-cdk inhibitor, it also performs cyclin-cdk-independent functions as the regulation of cytoskeleton rearrangements and cell motility. p27 deficiency has been associated with tumor aggressiveness and poor clinical outcome, although the mechanisms underlying this participation still remain elusive. We report here a new cellular function of p27 as a transcriptional regulator in association with p130/E2F4 complexes that could be relevant for tumorigenesis. We observed that p27 associates with specific promoters of genes involved in important cellular functions as processing and splicing of RNA, mitochondrial organization and respiration, translation and cell cycle. On these promoters p27 co-localizes with p130, E2F4 and co-repressors as histone deacetylases (HDACs) and mSIN3A. p27 co-immunoprecipitates with these proteins and by affinity chromatography, we demonstrated a direct interaction of p27 with p130 and E2F4 through its carboxyl-half. We have also shown that p130 recruits p27 on the promoters, and there p27 is needed for the subsequent recruitment of HDACs and mSIN3A. Expression microarrays and luciferase assays revealed that p27 behaves as transcriptional repressor of these p27-target genes (p27-TGs). Finally, in human tumors, we established a correlation with overexpression of p27-TGs and poor survival. Thus, this new function of p27 as a transcriptional repressor could have a role in the major aggressiveness of tumors with low levels of p27.

Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population.

OBJECTIVE: To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population. METHODS: We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires. RESULTS: The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated with greater BMI, following a co-dominant pattern (P = 0.009), whereas in the OHP this association was recessive (P = 0.004). Conversely, we did not find a significant association with BMI in the HCR group (P < 0.596). In the GP we found a significant interaction between the FTO SNP and education (P = 0.048). In the stratified analysis, no association of the FTO SNP with greater BMI in university subjects was detected (P = 0.786), whereas the association was observed in non-university subjects (P = 0.001). The FTO × education interaction (P = 0.020) was also observed in determining obesity risk in the GP. A-allele carriers had a greater risk of being obese only if they had no university education (OR: 1.56; 95%CI: 1.09-2.23 for TA and OR: 2.01; 95%CI: 1.27-3.26 for AA subjects). The interaction of the FTO with education remained significant even after adjustment for PA. CONCLUSIONS: The association of the FTO SNP with greater BMI and obesity risk in the GP was strongly modulated by education.

Scanning tunnelling spectroscopy study of paramagnetic superconducting ß''-ET(4)[(H(3)O)Fe(C(2)O(4))(3)]·C(6)H(5)Br crystals.

Scanning tunnelling spectroscopy (STS) and microscopy (STM) were performed on the paramagnetic molecular superconductor ß''-ET(4)[(H(3)O)Fe(C(2)O(4))(3)]·C(6)H(5)Br. Under ambient pressure, this compound is located near the boundary separating superconducting and insulating phases of the phase diagram. In spite of a strongly reduced critical temperature T(c) (T(c) = 4.0 K at the onset, zero resistance at T(c) = 0.5 K), the low temperature STS spectra taken in the superconducting regions show strong similarities with the higher T(c) ET κ-derivatives series. We exploited different models for the density of states (DOS), with conventional and unconventional order parameters to take into account the role played by possible magnetic and non-magnetic disorder in the superconducting order parameter. The values of the superconducting order parameter obtained by the fitting procedure are close to the ones obtained on more metallic and higher T(c) organic crystals and far above the BCS values, suggesting an intrinsic role of disorder in the superconductivity of organic superconductors and a further confirmation of the non-conventional superconductivity in such compounds.

[Time to first antibiotic dose in community-acquired pneumonia diagnosed in an emergency department]. / Tiempo hasta la administración de la primera dosis de antibiótico en las neumonías adquiridas en la comunidad en un Servicio de Urgencias Hospitalario.

BACKGROUND: Early antibiotic administration to patients diagnosed of community-acquired pneumonia (CAP) has been associated with a lower mortality. In the USA, its administration within four hours has been implanted as a quality standard. The objective of this work was to analyze, in a Spanish emergency department, the performance with patients with CAP, focusing on the administration of the first dose of antibiotic. PATIENTS AND METHOD: Clinics, welfare and organizational aspects have been analysed on 93 patients diagnosed of CAP in an emergency department in order to identify their influence on antibiotic administration within 4 hours. RESULTS: 46.2% of patients received antibiotics within 4 hours. The fact that patients were assisted in the higher complexity level showed a positive association with the antibiotic administration within 4 hours. On the contrary, presence of more than 10 patients waiting to be admitted showed a negative association. CONCLUSIONS: Early antibiotic administration in the CAP is possible. On order to guarantee a higher number of patients taking antibiotics within 4 hours we have to improve quality of care in both the emergency department (to guarantee correct classification according to the level of complexity) and in the hospital (management of beds to avoid delay in the admission of the patients).

Tiempo hasta la administración de la primera dosis de antibiótico en las neumonías adquiridas en la comunidad en un Servicio de Urgencias Hospitalario / Time to fi rst antibiotic dose in community-acquired pneumonia diagnosed in an emergency department

Introducción: La administración precoz de antibiótico en pacientes diagnosticados de una neumonía adquirida en comunidad (NAC) condiciona una disminución de la mortalidad. En EE. UU. Se ha implantado como estándar de calidad su administración en las primeras cuatro horas. El objetivo de este trabajo ha sido analizar retrospectivamente en un Servicio de Urgencias hospitalario (SUH) de nuestro medio la actuación con estos pacientes en lo que respecta a la administración de la primera dosis de antibiótico. Pacientes y método: Se han analizado aspectos clínicos, asistenciales y organizativos en 93 pacientes diagnosticados de NAC en un SUH para identificar su influencia en la administración de antibiótico en un plazo inferior a 4 horas. Resultados: El 46,2% de los pacientes recibió el antibiótico en las primeras cuatro horas. La asistencia en el área de mayor complejidad se asoció de forma positiva con la administración del antibiótico en las cuatro primeras horas. Por el contrario, la presencia de un mayor número de pacientes pendientes de ingreso en el SUH condicionó un menor cumplimiento de esta medida. Conclusiones: La administración precoz de antibiótico en la NAC es posible. El incremento en el cumplimiento de esta medida debe contemplar la mejora de la calidad asistencial tanto en aspectos organizativos propios del SUH (por ejemplo, con una adecuada clasificación inicial que garantice la atención de los pacientes acorde a su nivel de complejidad) como ajenos a él (gestión de camas hospitalarias que evite la demora en el ingreso desde el servicio) (AU)

Background: Early antibiotic administration to patients diagnosed of community-acquired pneumonia (CAP) has been associated with a lower mortality. In the USA, its administration within four hours has been implanted as a quality standard. The objective of this work was to analyze, in a Spanish emergency department, the performance with patients with CAP, focusing on the administration of the first dose of antibiotic. Patients and method: Clinics, welfare and organizational aspects have been analysed on 93 patients diagnosed of CAP in an emergency department in order to identify their influence on antibiotic administration within 4 hours. Results: 46.2% of patients received antibiotics within 4 hours. The fact that patients were assisted in the higher complexity level showed a positive association with the antibiotic administration within 4 hours. On the contrary, presence of more than 10 patients waiting to be admitted showed a negative association. Conclusions: Early antibiotic administration in the CAP is possible. On order to guarantee a higher number of patients taking antibiotics within 4 hours we have to improve quality of care in both the emergency department (to guaranty correct classification according to the level of complexity) and in the hospital (management of beds to avoid delay in the admission of the patients) (AU)

Quilotórax espontáneo en una lactante de 16 meses / Spontaneous chylothorax in a 16-month-old child

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Nuevas posibilidades de prevención y tratamiento de la enfermedad tromboembólica venosa / New prevention and therapy possibilities for thromboembolic venous disease

Fondaparinux es el primero de una nueva clase de antitrombóticos, los pentasacáridos sintéticos. Actúa inhibiendo el factor X activado. Ha demostrado ser superior a las heparinas de bajo peso molecular (HBPM) en la prevención de la enfermedad tromboembólica venosa (ETEV) tras cirugía ortopédica mayor, cirugía oncológica y enfermos médicos hospitalizados. Es tan eficaz y seguro como las HBPM en el tratamiento inicial de la trombosis venosa profunda y que la heparina no fraccionada en el tratamiento agudo de la embolia pulmonar sin inestabilidad hemodinámica. Puede sustituir a las HBPM en la profilaxis de ETEV y en el tratamiento de la trombosis venosa profunda con o sin embolia pulmonar y de la embolia pulmonar, hemodinámicamente estable, con o sin trombosis venosa (AU)

Fondaparinux is the leading molecule among a new class of antithrombotic drugs, the “synthetic pentasaccharides”. It acts by inhibiting activated Factor X. It has shown itself to be superior to low-molecular-weight heparins (LMWH) in the prevention of thromboembolic venous disease (TVD) after major orthopaedic surgery, oncologic suregry, and in hospitalised medical patients. It is as safe and effective as LMWH on the initial management of deep venous thrombosis, and as effective as non-fractionated heparin in the acute management of pulmonary embolism without haemodynamic instability. It may well replace LMWH in TVD prophylaxis and in the therapeutic management of deep venous thrombosis with or without pulmonary embolism and of haemodynamically stable pulmonary embolism with or without venous thrombosis (AU)

Taponamiento cardíaco: complicación grave e inusual en vías centrales / Cardiac tamponade: A severe and unusual complication in central lines

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Lesiones escleróticas diseminadas / Disseminated sclerotic lesions

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Prevalence of the methylenetetrahydrofolate reductase 677C > T mutation in the Mediterranean Spanish population. Association with cardiovascular risk factors.

Methylenetetrahydrofolate reductase (MT-HFR) is a key enzyme involved in folate metabolism. A common cytosine (C) to a thymine (T) mutation at nucleotide 677 (677C > T) in the MTHFR gene which converts an alanine residue to a valine, has been related with several biochemical phenotypes and with cardiovascular risk, depending on the population studied. Our objective was to estimate the prevalence of the 677C > T mutation in a large and randomly selected sample (289 men and 427 women) from the Mediterranean Spanish population, and to test the association between this genetic variant and some cardiovascular risk factors. For both genders, the prevalence of CC, CT and TT subjects was 32.0, 52.2 and 15.8%, respectively. The frequency (95% confidence interval) of the 677T allele was 0.44 (0.40-0.48) in men and 0.40 (0.37-0.44) in women. This prevalence was significantly different from other European countries, and among the highest reported in the world for any healthy population. We found no association between the 677C > T gene variants and age, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or diastolic blood pressure in men and women. However, in men, a statistically significant increase of systolic blood pressure with the number of mutant alleles was found (122.2 mmHg in CC, 125.1 mmHg in CT and 128.5 mmHg in TT subjects; p for trend = 0.030). This association remained significant (p = 0.047) even after adjustment for age, BMI, alcohol consumption, tobacco smoking, education and physical activity.

Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation.

OBJECTIVE: To investigate the association between the Trp64Arg beta3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18-68 years). MEASUREMENTS: Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism. RESULTS: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women. However, after adjustment for covariates, these associations only remained statistically significant (P < 0.02) in women. Moreover, in women, a statistically significant interaction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women. CONCLUSIONS: The Trp64Arg mutation was associated with BMI and lipids in men. In women, an additional gene-gene interaction with the LPL-HindIII polymorphism may explain the results.

[Sensitivity, specificity and predictive value of the genetic analysis of SLC3A1 gene variants used for the diagnosis of cystinuria among the spanish population]. / Sensibilidad, especificidad y valor predictivo del análisis genético de variantes en el gen SLC3A1 aplicado al diagnóstico de cistinuria en población española.

OBJECTIVE: To test the clinical usefulness of the analysis of point mutations R452W, M467T, 114C > A, 231T > A, 1136 + 3delT and 1332 + 7T > C in the gene SLC3A1 as well as their possible haplotypes used for the diagnosis of cystinuria in the mediterranean spanish population. MATERIAL AND METHODS: A total of 48 patients with cystinuria, 44 relatives without cystinuria, and 81 healthy controls were studied. A genetic analysis was conducted in order to identify variants in the gene SLC3A1. The sensitivity, specificity, and predictive value for each genetic variant and for the possible haplotypes were calculated. RESULTS: The specificity of mutations M467T, R452W, and 231T > A used for the diagnosis of cystinuria in the general population or for the different subtypes of cystinuria in involved families, was higher than 90%; nevertheless, none of the analysed variants reached a sensitivity higher than 80%. In the study of haplotypes, the highest sensitivity was obtained with the haplotype CTTT (83.8%); however, its specificity and predictive value were low (20.6% and 53.4%, respectively). CONCLUSIONS: The studied genetic variants did not show enough clinical usefulness.

Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: ecogenetic studies in a Mediterranean Spanish population.

To investigate APOE gene--environment interaction effects on plasma lipid concentrations, we conducted a cross-sectional study in a Mediterranean Spanish population consisting of 396 men and 513 women aged 18 to 66 years. The frequency of the epsilon 4 variant was 0.071 (95% confidence interval 0.059, 0.082), confirming the lower frequency of this allele in Southern Europe. In general, the carriers of the epsilon 2 variant had lower concentrations (P <.05) of total and low-density lipoprotein cholesterol (LDL-C), carriers of the epsilon 3 variant had intermediate concentrations, and carriers of the epsilon 4 variant had higher concentrations (P <.05) in both sexes, even after multivariate adjustment for age, body mass index, alcohol consumption, tobacco smoking, physical activity, marital status, and education. However, when the homogeneity of allelic effects according to environmental factors was tested, significant interaction terms were found. In women, an important interaction between alcohol consumption and the APOE polymorphism in determining LDL-C concentrations was found (P <.003). LDL-C concentrations in female drinkers with the epsilon 2 variant were significantly lower (P <.014) than in nondrinkers with the epsilon 2 variant. Likewise, in female drinkers with the epsilon 4 variant, LDL-C concentrations were also significantly (P <.010) lower than in nondrinkers with the epsilon 4 variant. Moreover, in female drinkers, LDL-C concentrations did not differ between carriers of the epsilon 4 and the epsilon 3 variants, and in nondrinkers, LDL-C concentrations did not differ between carriers of the epsilon 2 and the epsilon 3 variants. We also found a statistically significant interaction effect (P <.001) between the APOE polymorphism and physical activity in determining high-density lipoprotein cholesterol concentrations in men. Our results indicate that environmental factors are important modulators of the effect of the APOE polymorphism on plasma lipid concentrations.

Hybrid molecular materials based upon organic pi-electron donors and metal complexes. Radical salts of bis(ethylenethia)tetrathiafulvalene (BET-TTF) with the octahedral anions hexacyanoferrate(III) and nitroprusside. The first kappa phase in the BET-TTF family.

The synthesis, structure, and physical characterization of two new radical salts formed with the organic donor bis(ethylenethia)tetrathiafulvalene (BET-TTF) and the octahedral anions hexacyanoferrate(III), [Fe(CN)(6)](3-), and nitroprusside, [Fe(CN)(5)NO](2-), are reported. These salts are (BET-TTF)(4)(NEt(4))(2)[Fe(CN)(6)] (1) (monoclinic space group C2/c with a = 38.867(7) A, b = 8.438(8) A, c = 11.239(6) A, beta = 90.994(9) degrees, V = 3685(4) A(3), Z = 4) and (BET-TTF)(2)[Fe(CN)(5)NO].CH(2)Cl(2) (2) (monoclinic space group C2/c with a = 16.237(6) A, b = 18.097(8) A, c = 12.663(7) A, beta = 106.016(9) degrees, V = 3576(3) A(3), Z = 4). In salt 1 the organic BET-TTF molecules are packed in orthogonal dimers, forming the first kappa phase observed for this donor. The analysis of the bond distances and the electronic and IR spectra suggests a degree of ionicity of 1/4 per BET-TTF molecule, in agreement with the stoichiometry of the salt. The electrical properties show that 1 is a semiconductor with a high room-temperature conductivity (11.6 S cm(-1)) and a low activation energy (45 meV), in agreement with the band structure calculations. The magnetic susceptibility of 1 shows, besides the paramagnetic contribution from the anion, a temperature-independent paramagnetism (TIP) of the Pauli type due to the electronic delocalization observed at high temperatures in the organic sublattice. This Pauli type paramagnetism is confirmed by the ESR spectra that also show a Dysonian line when the magnetic field is parallel to the conducting plane, typical of metallic and highly conducting systems. Salt 2 presents an unprecedented packing of the organic molecules that form zigzag tunnels where the anions and the solvent molecules are located. The stoichiometry indicates that all the BET-TTF molecules bear a charge of +1, and accordingly, 2 behaves as a semiconductor with a very low room-temperature conductivity. The magnetic properties of this salt indicate that the unpaired electrons on the organic molecules are strongly antiferromagnetically coupled, giving rise to a diamagnetic behavior of 2, as the nitroprusside anion is also diamagnetic.

Sensibilidad, especificidad y valor predictivo del análisis genético de variantes en el gen SLC3A1 aplicado al diagnóstico de cistinuria en población española / Sensitivity, specificity and predictive value of the genetic analysis of SLC3A1 gene variants used for the diagnosis of cystinuria among the spanish population

Objetivo. Estimar la validez clínica del análisis de las mutaciones puntuales R452W, M467T, 114C > A, 231T > A, 1136 + 3delT y 1332 + 7T > C en el gen SLC3A1, así como de sus posibles haplotipos aplicados al diagnóstico de cistinuria en población mediterránea española. Material y métodos. Se han estudiado 48 pacientes con cistinuria, 44 familiares sin cistinuria y 81 controles sanos. Se realizó un análisis genético para la identificación de variantes en el gen SLC3A1. Se calculó la sensibilidad, especificidad y valor predictivo para cada variante genética y para los posibles haplotipos. Resultados. La especificidad de las mutaciones M467T, R452W y 231T > A aplicadas al diagnóstico de cistinuria en población general o para los diferentes subtipos de cistinuria en familias afectadas fue superior al 90 por ciento; sin embargo, ninguna variante analizada alcanzó una sensibilidad superior al 80 por ciento. En el estudio de haplotipos, la sensibilidad más alta se obtuvo con el haplotipo CTTT (83,8 por ciento); sin embargo, su especificidad y valor predictivo fueron bajos (20,6 por ciento y 53,4 por ciento, respectivamente).Conclusiones. Las variantes genéticas estudiadas no mostraron suficiente validez clínica (AU)