A novel risk prediction tool for contrast-induced nephropathy in patients with chronic kidney disease who underwent diagnostic coronary angiography.

OBJECTIVE: The incidence of contrast-induced nephropathy (CIN) is higher than 20% in patients with chronic kidney disease. In this study, we sought to define the predictors of CIN and develop a risk prediction tool in patients with chronic kidney disease. PATIENTS AND METHODS: Patients aged 18 years and older who underwent invasive coronary angiography with an iodine-based contrast media between March 2014 and June 2017 were retrospectively analyzed. Independent predictors for CIN development were identified and a new risk prediction tool was created that included these predictors. RESULTS: In total, 283 patients included in the study were divided into those who developed CIN (n=39, 13.8%) and those who did not (n=244, 86.2%). Male gender (OR: 4.874, 95% CI: 2.044-11.621), LVEF (OR: 0.965, 95% CI: 0.936-0.995), diabetes mellitus (OR: 1.711, 95% CI: 1.094-2.677), and e-GFR (OR: 0.880, 95% CI: 0.845-0.917), were identified as independent predictors for the development of CIN in the multivariate analysis. A new scoring system has been designed that can score a minimum of 0 and a maximum of 8 points. Patients with a new scoring system score of ≥4 were at approximately 40 times higher risk of developing CIN than others (OR: 39.9, 95% CI: 5.4-295.3). The area under the curve value of CIN's new scoring system was 0.873 (95% CI, 0.821-0.925). CONCLUSIONS: We found that four easily accessible and routinely collected variables, including sex, diabetes status, e-GFR, and LVEF, were independently associated with the development of CIN. We believe that using this risk prediction tool in routine clinical practice may guide physicians to use preventive medications and techniques in high-risk patients for CIN.

Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM. RESULTS: Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001). CONCLUSIONS: Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Effect of Decorin and Bevacizumab on oxygen-induced retinopathy in rat models: A comparative study.

Purpose: The aims of this study were to evaluate the effects of decorin (DCN) in rat oxygen-induced retinopathy (OIR) model and to compare the results with those of bevacizumab. Methods: Twenty-eight newborn Sprague-Dawley rats were randomly divided into four groups. Group I (control): normoxia plus intraperitoneal (ip) normal saline (NS), Group II (sham): OIR plus ip NS, Group III (DCN): OIR plus ip 0.1 mg/kg DCN, and Group IV (bevacizumab): OIR plus ip 2.5 mg/kg bevacizumab. The OIR model was induced by cycling the oxygen concentration between 50% and 10% every 24 h for 14 days following their birth. In all groups, injections were administered on postnatal day (PD) 15. All animals were sacrificed and their right eyes were enucleated on PD 18. The nuclei of neovascular endothelial cells on the vitreal side of the inner limiting membrane were counted, and vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF)-α immunoreactivity were detected in histopathological and immunohistochemical examinations. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses of the data. Results: In Groups II, III, and IV, the mean neovascular cell nuclei counts were 13.14 ± 1.34, 6.57 ± 1.51, and 6.71 ± 1.49, respectively. The mean neovascular cell nuclei count was significantly reduced in treatment groups compared with sham group (P < 0.001). In immunohistochemical staining, the immunoreactivity of VEGF was 0.07 ± 0.02, 0.97 ± 0.21, 0.37 ± 0.12, and 0.23 ± 0.17, respectively. Likewise, immunoreactivity of TNF-α was 0.02 ± 0.02, 1.11 ± 0.36, 0.37 ± 0.13, and 0.62 ± 0.21, respectively. VEGF and TNF-α immunoreactivity increased markedly in the sham group compared with those in the control group (P < 0.001). VEGF and TNF-α immunoreactivity of treatment groups decreased significantly compared to sham group (P < 0.001). Conclusion: The beneficial effects obtained by DCN administration in OIR model were comparable to the effects of bevacizumab.

Towards the Limits of Existence of Nuclear Structure: Observation and First Spectroscopy of the Isotope

The most remote isotope from the proton dripline (by 4 atomic mass units) has been observed: ^{31}K. It is unbound with respect to three-proton (3p) emission, and its decays have been detected in flight by measuring the trajectories of all decay products using microstrip detectors. The 3p emission processes have been studied by the means of angular correlations of ^{28}S+3p and the respective decay vertices. The energies of the previously unknown ground and excited states of ^{31}K have been determined. This provides its 3p separation energy value S_{3p} of -4.6(2) MeV. Upper half-life limits of 10 ps of the observed ^{31}K states have been derived from distributions of the measured decay vertices.

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.

BACKGROUND: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. PATIENTS AND METHODS: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. RESULTS: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. CONCLUSIONS: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. CLINICALTRIALS.GOV NUMBER: NCT01704703. EUDRACT NUMBER: 2012-001955-38.

Expression of radial glial markers (GFAP, BLBP and GS) during telencephalic development in the catshark (Scyliorhinus canicula).

Radial glial cells (RGCs) are the first cell populations of glial nature to appear during brain ontogeny. They act as primary progenitor (stem) cells as well as a scaffold for neuronal migration. The proliferative capacity of these cells, both in development and in adulthood, has been subject of interest during past decades. In contrast with mammals where RGCs are restricted to specific ventricular areas in the adult brain, RGCs are the predominant glial element in fishes. However, developmental studies on the RGCs of cartilaginous fishes are scant. We have studied the expression patterns of RGCs markers including glial fibrillary acidic protein (GFAP), brain lipid binding protein (BLBP), and glutamine synthase (GS) in the telencephalic hemispheres of catshark (Scyliorhinus canicula) from early embryos to post-hatch juveniles. GFAP, BLBP and GS are first detected, respectively, in early, intermediate and late embryos. Expression of these glial markers was observed in cells with radial glia morphology lining the telencephalic ventricles, as well as in their radial processes and endfeet at the pial surface and their expression continue in ependymal cells (or tanycytes) in early juveniles. In addition, BLBP- and GS-immunoreactive cells morphologically resembling oligodendrocytes were observed. In late embryos, most of the GFAP- and BLBP-positive RGCs also coexpress GS and show proliferative activity. Our results indicate the existence of different proliferating subpopulations of RGCs in the embryonic ventricular zone of catshark. Further investigations are needed to determine whether these proliferative RGCs could act as neurogenic and/or gliogenic precursors.

Scattering of the Halo Nucleus

Angular distributions of the elastic, inelastic, and breakup cross sections of the halo nucleus ^{11}Be on ^{197}Au were measured at energies below (E_{lab}=31.9 MeV) and around (39.6 MeV) the Coulomb barrier. These three channels were unambiguously separated for the first time for reactions of ^{11}Be on a high-Z target at low energies. The experiment was performed at TRIUMF (Vancouver, Canada). The differential cross sections were compared with three different calculations: semiclassical, inert-core continuum-coupled-channels and continuum-coupled-channels ones with including core deformation. These results show conclusively that the elastic and inelastic differential cross sections can only be accounted for if core-excited admixtures are taken into account. The cross sections for these channels strongly depend on the B(E1) distribution in ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and halo degrees of freedom in ^{11}Be.

Observation and Spectroscopy of New Proton-Unbound Isotopes ³°Ar and ²9Cl: An Interplay of Prompt Two-Proton and Sequential Decay.

Previously unknown isotopes (30)Ar and (29)Cl have been identified by measurement of the trajectories of their in-flight decay products (28)S+p+p and (28)S+p, respectively. The analysis of angular correlations of the fragments provided information on decay energies and the structure of the parent states. The ground states of (30)Ar and (29)Cl were found at 2.25(-0.10)(+0.15) and 1.8±0.1 MeV above the two- and one-proton thresholds, respectively. The lowest states in (30)Ar and (29)Cl point to a violation of isobaric symmetry in the structure of these unbound nuclei. The two-proton decay has been identified in a transition region between simultaneous two-proton and sequential proton emissions from the (30)Ar ground state, which is characterized by an interplay of three-body and two-body decay mechanisms. The first hint of a fine structure of the two-proton decay of (30)Ar*(2(+)) has been obtained by detecting two decay branches into the ground and first-excited states of the (28)S fragment.

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale.

The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens.

PURPOSE: We are trying to identify predictive factors of high risk of toxicity by analyzing candidate genes in the irinotecan pathways in order to identify useful tools to improve mCRC patient management under real practice conditions. METHODS: Genomic DNA was genotyped for UGT1A1 (*28, *60 and *93) from all 101 patients, and irinotecan dose was 180 mg/m(2) every second week. Clinical data were obtained by retrospective chart review. The primary endpoint is to find out whether the pharmacogenetic test in the clinical practice may predict toxicity. RESULTS: Grade 3/4 diarrhea occurred in twelve patients and required dose reduction in six patients, and neutropenia reached grade 3/4 in 19 patients (only one patient with *28/*28 genotype). The UGT1A1*93 seemed to relate with grade 3/4 neutropenia but only in the heterozygote state (G/A), p = 0.071, and UGT1A*60 showed no association with neutropenia. Twenty-eight percentage of patients required the use of G-CSF; 64.3% of them harbored *1/*28 or *28/*28 genotypes, p = 0.003. Thirty-seven (36.6%) patients required dose reduction of irinotecan and/or 5-FU owing to toxicity, mainly neutropenia and diarrhea. No significant association was detected between *28, *60 and *93 UGT1A variants and severe irinotecan-associated hematologic or GI toxicity. CONCLUSION: The impact of increased risk of toxicity attributed to the UGT1A variants may be offset by irinotecan in clinical practice by dose reduction or the use of colony-stimulating factor.

Asociación de otras drogas de abuso en la intoxicación por cocaína / Cocaine intoxication in association with other drugs of abuse

El objetivo del presente trabajo ha sido llevar a cabo un análisis de las urgencias atendidas en un hospital urbano de tercer nivel que se han relacionado con el consumo de cocaína. Para ello se ha realizado un estudio retrospectivo, con exclusión del área de pediatría y ginecología, durante los años 2005 y 2006. Se revisaron todas las asistencias clínicas que consultaron por intoxicación por cocaína. Los datos fueron analizados con el paquete estadístico SPSS 15.0 para windows. Durante el periodo de estudio se produjeron 1.531 intoxicaciones (1,2% del total de las urgencias). De éstas, 327 eran por cocaína (21,4% de las intoxicaciones). La edad media fue de 31 (8) años y la moda de 26 años. Un 76,5% eran varones. El 69,1% ingresaron en ambulancia. La mayor afluencia se produjo en fin de semana (46,8%) y en horario nocturno (54,1%). El 53,2% eran consumidores habituales y el 25,4% esporádicos. Un 55,7% asociaron más de 2 drogas: el 53,5% alcohol, el 31,2% opiáceos, el 17.4% benzodiacepinas, el 17,1% cannabis, el 11,3% GHB y el resto otras drogas. El 77,1% consumieron en un lugar público. Tenían antecedentes de intoxicaciones previas un 59,3%. El 93% presentaban síntomatología: (52,6% neurológicos, 48% conductuales, 28,4% cardiovasculares, 19% respiratorios y 8,3% digestivos). Se administraron antídotos a un 20,5%. El destino final fue alta en las primeras 12 horas en el 60,9%, con solo un 5,7% de ingresos. Se realizó valoración psiquiátrica en el 21,1%. En conclusión, el perfil del usuario que consulta por intoxicación por cocaína es un varón de 26 años traído en ambulancia de un lugar público, en fin de semana, en horario nocturno, consumidor habitual, con sintomatología cardiológica y neurológica y dado de alta en menos de 12 horas. La intoxicación aguda por cocaína no es pura. Destaca la asociación de alcohol, opiáceos y benzodiacepinas. Menos de una cuarta parte fueron valorados por Psiquiatría (AU)

The main of this study was to analyze all patients with cocaine intoxication attended in the emergency department of a tertiary-care hospital. For this, a retrospective study for the years 2005 and 2006, excluding peadiatric and gynecological areas, has been carried out. All cases in which the main reason for seeking urgent medical care was cocaine intoxication were reviewed. Data were analyzed with the SPSS statistical package (version 15.0) for Windows. During the study period, a total of 1531 subjects with drug of abuse intoxication were attended, which accounted for 1.2% of all patients attended in the emergency department. Cocaine was the drug of abuse responsible for the intoxication in 327 cases (21.4% of all intoxications). The mean (SD) age of the patients was 31 (8) years (mode 26 years). A total of 76.5% were men, and 69.1% arrived to the emergency department in ambulance. A large percentage of subjects were attended on weekends (46.8%) and during the night shift (54.1%). A total of 53.2% were regular cocaine consumers and 25.4% consumed the drug sporadically. In 55.7% of the cases, more than two drugs were concomitantly consumed, including alcohol in 53.5% of cases, opioids in 31.2%, benzodiazepines in 17.4%, cannabis in 17.1%, gamma hydroxybutyric acid in 11.3%, and other drugs in the remaining cases. Drugs were consumed in a public place in 77.1% of cases. History of previous episodes of intoxication was recorded in 59.3% of cases. Symptoms were present in 93% of subjects (neurological in 52.6%, behavioural in 48%, cardiovascular in 28.4%, respiratory in 19%, and gastrointestinal in 8.3%). Antidotes were administered in 20.5% of cases. A total of 60.9% of subjects were discharged from the emergency department within the first 12 hours and only 5.7% were admitted to the hospital. Twenty-one percent of subjects underwent psychiatric assessment. In conclusion, the profile of a subject with cocaine intoxication attended in the emergency department is a man of 26 years of age, transferred in ambulance from a public place, on weekends and at night, regular cocaine consumer, presenting with neurological and cardiological symptoms, and discharged from the emergency department in less than 12 hours after admission. Cocaine intoxication occurred frequently in association with alcohol, opioids, and benzodiazepine use. Less than one fourth of subjects underwent psychiatric assessment (AU)

Comparative analysis of Met-enkephalin, galanin and GABA immunoreactivity in the developing trout preoptic-hypophyseal system.

We studied the organization of Met-enkephalin-containing cells and fibers in the developing preoptic-hypophyseal system of the brown trout (Salmo trutta fario) by immunohistochemistry and determined the relationship of these cells and fibers to the galaninergic and GABAergic systems. Met-enkephalin immunoreactivity was observed in cells in the preoptic area, the hypothalamus and the pituitary of late larvae. In the hypophysis, a few Met-enkephalin-containing cells were present in all divisions of the adenohypophysis, and some immunoreactive fibers were present in the interdigitations of the neural lobe with the proximal pars distalis. Concurrently, GABAergic fibers innervated the anterior and posterior neural lobe. Galanin cells coexisted with Met-enkephalin cells in neuronal groups of the preoptic-hypophyseal system. Galaninergic and GABAergic fibers innervated the preoptic and hypothalamic areas, but GABAergic fibers containing galanin were not observed. These results indicate that Met-enkephalin, galanin and GABA may modulate neuroendocrine activities in the preoptic area, hypothalamus and pituitary during the transition from larval to juvenile period. To better know how the development of the trout preoptic-hypophyseal system takes place, we studied the patterns of cell proliferation and expression of Pax6, a conserved transcription factor involved in the hypophysis development. Pax6 expressing cells and proliferating cells were present in the Rathke's pouch, the hypothalamus and the hypophysis of early larvae. In late larvae, Pax6 expression was no longer observed in these areas, and the density of proliferating cells largely decreased throughout development, although they remained in the hypophysis of late larvae and juveniles, suggesting that Pax6 might play an important role in the early regionalization of the pituitary in the trout.

Effects of compressed seasonally changing day-length cycles on spawning performance, production of viable eggs and levels of vitellogenin in plasma in female yellowtail snapper Lutjanus argentiventris.

Reproduction in yellowtail snapper Lutjanus argentiventris took place after compressing the seasonally changing day length into a 3 month period applied during two consecutive winters, with the longest and shortest days in December and February, respectively. During the first winter, there was no clear peak of days of spawning and the production of viable eggs was similar from the longest and throughout the decreasing day lengths until reproduction ceased. The level of plasma vitellogenin rose abruptly to a maximum concentration during the increasing day length and then decreased dramatically before the longest day length. During the second winter, a clear peak in the number of days of spawning and the highest production of viable eggs occurred around the longest day length. These results showed that it is feasible to synchronize day length between winter-induced and natural summer and autumn reproduction to produce eggs and larvae during the year.

Disnea súbita después del terremoto / After the earthquake sudden dyspnea

Fat embolism syndrome (FES) remains a diagnostic challenge for physicians. It is commonly as associated with fractures of long bones and it is a major source of morbidity and mortality inpatients with multiple injuries. Overall mortality is between 5-15 percent in all studies. These facts motivate us to present the case of a young woman suffering bone fractures in both legs during the earthquake in Chile on February 27, 2010. She presented a FES 72 hours later. It is important to understand this syndrome, as it can be confused with other serious diseases that require different management. We should be able to have a high FES suspicion in the appropriate context, in as much as an early diagnosis, and treatment may improve the prognosis of this severe condition.

El síndrome de embolia grasa (SEG) sigue siendo un reto diagnóstico para los médicos. Se asocia fundamentalmente en fracturas de los huesos largos y es una importante fuente de morbilidad y mortalidad en pacientes politraumatizados. La mortalidad general se encuentra entre el 5 a 15 por ciento en todos los estudios. Esto nos motiva a presentar el caso de una mujer joven que 72 horas después de fracturas sufridas durante el terremoto ocurrido en Chile el 27 de febrero del 2010, presentó un SEG. Es importante conocer este síndrome, ya que se puede confundir con otras patologías graves que requieren un manejo distinto y al tener una alta sospecha en el contexto adecuado, se permite un diagnóstico oportuno, tratamiento precoz y mejorar el pronóstico.

Antimicrobial activity of the extracts and physalin D from Physalis alkekengi and evaluation of antioxidant potential of physalin D.

Physalis alkekengi L. (Solanaceae) is a popular plant in traditional European and Chinese folk medicine, and it has been reported to have many ethnopharmacological properties including antifungal, anti-cough, anti-inflammatory, analgesic, and febricide activities. Some active components from Physalis species have been investigated. However, no antimicrobial activity studies on extracts and physalins of P. alkekengi have been carried out. In this study, we attempted to identify the possible antimicrobial activities of the methanol extract from aerial parts of P. alkekengi and the dichloromethane extract from calyces of the plant. The extracts were tested against five Gram-positive and five Gram-negative bacteria and five Candida species by using disk diffusion and broth microdilution methods. The extracts were fractionated to isolate physalins using chromatographic techniques, and physalin D was isolated from the extracts. The structure of the compound was elucidated on the basis of (1)H-NMR spectroscopic study, and confirmed by comparison with a reference sample and literature data. Results indicated that all the extracts and physalin D were characterized by antibacterial action, especially against Gram-positive bacteria, with MIC values between 32 and 128 microg/mL. The methanol extract had moderate activity against fungi at MICs ranging from 128 to 512 microg/mL, but the dichloromethane extract and physalin D had low activity against fungi at MICs ranging from 256 to 512 microg/mL. Additionally, the antioxidant activity of physalin D was evaluated by qualitative DPPH (1,1-diphenyl-2-picrylhydrazyl) radical and TBA (thiobarbituric acid) assays. Physalin D showed low antioxidant activity with an IC(50) value of >or= 10 +/- 2.1.

Epidemiologic impact of blood culture practices and antibiotic consumption on pneumococcal bacteraemia in children.

This study examined the roles of two different diagnostic approaches to children with fever of unknown origin in determining the patterns of pneumococcal bacteraemia in two Spanish regions by comparing their main epidemiologic characteristics. Whereas a blood culture is routinely obtained in this setting in Navarre, this is not generally the case in Majorca. Additionally, the potential role of antibiotic consumption in each region was also analysed. Cumulative incidences in children under the age of 14 years were 26.6 per 100,000 child-years in Navarre (121.1 in children <2 years of age) and 7.3 per 100,000 child-years in Majorca (33.3 in children <2 years of age). In contrast, the incidences per 1,000 blood cultures were similar in both regions. The relative risks of occult bacteraemia, bacteraemic pneumonia and meningitis among the children of Navarre compared to Majorcan children were 11.8, 2.6 and 0.8, respectively. The risk for less virulent (vaccine serotypes plus 6A, 19A and 23A) and for more virulent serotypes (1 and 7) was 4.9 and 3.1 times higher in Navarre, respectively. The number of 7-valent pneumococcal conjugate vaccine (PCV7) doses administered between 2003 and 2004 were also higher in Navarre. Conversely, antibiotic resistance and paediatric prescriptions for broad-spectrum antibiotics were greater in Majorca. Although the most salient differences between both regions, including the effectiveness of pneumococcal conjugate vaccine in Navarre, appeared to be confounded by the higher frequency of blood cultures taken there, certain differences in serotype composition may be explained by the higher antibiotic consumption in Majorca.

In vitro antileishmanial activity of Adana propolis samples on Leishmania tropica: a preliminary study.

Propolis (bee glue) is a natural resinous hive product, collected from various plant sources. It has attracted much attention as a useful substance applied in medicine due to its pharmacological activities. It was aimed to investigate the in vitro effects of an ethanolic extract of Adana propolis samples on the growth of Leishmania tropica. Parasite cells were treated with five concentrations (25, 50, 100, 50, 500, and 750 microg/ml) of the propolis. The number of promastigotes in each concentration was calculated using a hemocytometer slide at 24, 48, and 72 h after being harvested. In the experiments, it was determined that the concentrations up to 100 mug/ml of the propolis did not exhibit antileishmanial activity against the parasites cells. At these concentrations, there was no changes in terms of morphologically. In addition, there was no statistically significant difference in terms of cell count between control and these three groups (p > 0.05). However, in culture media containing the propolis samples at 250, 500, and 750-microg/ml concentrations, statistically significant differences in cell counts were observed, as compared to the control group (p < 0.05). Our results demonstrate that ethanolic extracts of Adana propolis samples reduce the proliferation of L. tropica parasites significantly.

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine.

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

Radioquimioterapia neoadyuvante en cáncer gástrico T4 localmente irresecable: resultados preliminares / Chemoradiotherapy in patients with non resectable gastric cancer: report of 10 patients

En el caso de pacientes con cáncer gástrico T4, puede estar indicada la quimiorradioterapia si no es posible la resección de las estructuras infiltradas. Analizamos 10 pacientes con cáncer gástrico irresecable (8 hombres, 2 mujeres) tratados por nosotros en el periodo 2003-2005. Después de la laparotomía exploradora, los pacientes con cáncer gástrico localmente avanzados e irresecables son tratados con RT-QT concomitante 2 semanas después de la laparotomía. El tratamiento consistió en radioterapia a dosis de 45 Gy en 25 fracciones de 1.8 Gy, 5 veces por semana por 5 semanas sobre estómago y linfáticosregionales, y 5 FU en 1ª y 5º semana (425mg/m2) o Capecitabina 825 mg/m2 diarios, en dos dosis, cada12 hrs. Un mes después se realiza la segunda laparotomía con resección del estómago y linfadenectomía en casos de remisión total o parcial de la enfermedad. Todos los carcinomas fueron proximales. Nueve pacientes se reintervinieron, un paciente tuvo progresión de la enfermedad. Un paciente fue nuevamente irresecable y ocho fueron sometidos a una gastrectomía total D2. Se logró respuesta patológica completa en tres casos (no había cáncer residual en el estómago ni en los ganglios) y parcial en cinco. Creemos que en cáncer gástrico T4 localmente irresecable la RT-QT seguida de cirugía es una buena alternativa terapéutica.