Urinary levels of organophosphate pesticides and predictors of exposure in pre-school and school children living in agricultural and urban communities from south Spain.

BACKGROUND: Despite the widespread use of organophosphate (OP) pesticides, information on predictors of children's exposure to such pesticides is scarce. OBJECTIVE: To assess exposure to OP pesticides in children 3-11 year-old living in agricultural communities and urban areas from Andalusia (Southern Spain), and to identify the main determinants of exposure. METHODS: A longitudinal study was conducted in children 3-11-year-old children living in agricultural communities and urban areas from the provinces of Almeria, Granada and Huelva (Andalusia, Spain) between 2010 and 2011. Urinary levels of six dialkylphosphate (DAP) metabolites were measured by UHPLC-QqQ-MS/MS at the periods of low and high pesticide use in the agriculture (LPU and HPU, respectively). Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and diet, among other relevant factors, was obtained from questionnaires administered to the mothers. RESULTS: A total of 559 and 597 children participated in LPU and HPU periods, respectively. The proportion of urine samples below LOD was 67.4% for ΣDMs (sum of dimethyl metabolites), 77% for ΣDEs (sum of diethyl metabolites) and 58.5% for ΣDAPs (sum of total dialkylphosphate metabolites) in LPU period, and 50.4% for ΣDMs, 65.3% for ΣDEs and 43.9% for ΣDAPs in HPU period. Significantly greater urinary ΣDAP, ΣDM and ΣDE levels were observed in HPU relative to LPU period. Maternal schooling years, proximity of the house to crops or greenhouses, use of insecticides at home, spraying the garden with pesticides, storage of pesticides at home, house cleaning frequency, as well as child's frequency of bath/shower, were found to be the major predictors of urinary levels of ΣDAP. Likewise, not washing fruit and vegetables before consumption and banana consumption were also identified as determinants of the exposure levels. CONCLUSIONS: Urinary levels of metabolites of OP pesticides found in this study were relatively lower compared to similar studies. DAP levels were significantly increased in HPU period. Maternal schooling years and variables related to residential environment and home exposures were identified as the most relevant determinants of DAP metabolites. Regarding diet, banana consumption and not washing fruit before consumption were also identified as determinants of the exposure levels. This study contributes to improve our knowledge on the main sources and determinants of children exposure to OPS, and given that children are more vulnerable than adults this information is essential to reduce children exposure and protect their health.

Comparative Population Plasma and Tissue Pharmacokinetics of Micafungin in Critically Ill Patients with Severe Burn Injuries and Patients with Complicated Intra-Abdominal Infection.

Severely burned patients have altered drug pharmacokinetics (PKs), but it is unclear how different they are from those in other critically ill patient groups. The aim of the present study was to compare the population pharmacokinetics of micafungin in the plasma and burn eschar of severely burned patients with those of micafungin in the plasma and peritoneal fluid of postsurgical critically ill patients with intra-abdominal infection. Fifteen burn patients were compared with 10 patients with intra-abdominal infection; all patients were treated with 100 to 150 mg/day of micafungin. Micafungin concentrations in serial blood, peritoneal fluid, and burn tissue samples were determined and were subjected to a population pharmacokinetic analysis. The probability of target attainment was calculated using area under the concentration-time curve from 0 to 24 h/MIC cutoffs of 285 for Candida parapsilosis and 3,000 for non-parapsilosis Candida spp. by Monte Carlo simulations. Twenty-five patients (18 males; median age, 50 years; age range, 38 to 67 years; median total body surface area burned, 50%; range of total body surface area burned, 35 to 65%) were included. A three-compartment model described the data, and only the rate constant for the drug distribution from the tissue fluid to the central compartment was statistically significantly different between the burn and intra-abdominal infection patients (0.47 ± 0.47 versus 0.15 ± 0.06 h(-1), respectively; P < 0.05). Most patients would achieve plasma PK/pharmacodynamic (PD) targets of 90% for non-parapsilosis Candida spp. and C. parapsilosis with MICs of 0.008 and 0.064 mg/liter, respectively, for doses of 100 mg daily and 150 mg daily. The PKs of micafungin were not significantly different between burn patients and intra-abdominal infection patients. After the first dose, micafungin at 100 mg/day achieved the PK/PD targets in plasma for MIC values of ≤0.008 mg/liter and ≤0.064 mg/liter for non-parapsilosis Candida spp. and Candida parapsilosis species, respectively.

First resuscitation of critical burn patients: progresses and problems.

Currently, the aim of the resuscitation of burn patients is to maintain end-organ perfusion with fluid intake as minimal as possible. To avoid excess intake, we can improve the estimation using computer methods. Parkland and Brooke are the commonly used formulas, and recently, a new, an easy formula is been used, i.e. the 'Rule of TEN'. Fluid resuscitation should be titrated to maintain the urine output of approximately 30-35 mL/h for an average-sized adult. The most commonly used fluids are crystalloid, but the phenomenon of creep flow has renewed interest in albumin. In severely burn patients, monitoring with transpulmonary thermodilution together with lactate, ScvO2 and intraabdominal pressures is a good option. Nurse-driven protocols or computer-based resuscitation algorithms reduce the dependence on clinical decision making and decrease fluid resuscitation intake. High-dose vitamin C, propranolol, the avoidance of excessive use of morphine and mechanical ventilation are other useful resources.

Acute kidney injury in critically burned patients resuscitated with a protocol that includes low doses of Hydroxyethyl Starch.

Acute kidney injury (AKI) is an important complication in burn patients. Recently, it has been recommended that hydroxyethyl starch (HES) be avoided in burn patients because it increases the incidence of AKI. Our purpose was to study incidence of AKI in critically ill burn patients resuscitated with Ringer's solution and supplements of HES. We conducted an observational study of 165 patients admitted to the critical care burn unit (with 30 ± 15% TBSA burned). The main outcome measures were incidence of AKI, contributions of colloids and crystalloids, various severity scores, comorbidities, complications and mortality. According to the RIFLE criteria, 10 (6.1%) patients presented with Risk, 11 (6.7%) presented with Injury and 11 (6.7%) presented with Failure. According to the AKIN criteria, 9.7% presented stage I, 3% stage II and 10.3% stage III. Replacement therapy (RRT) was performed in 15 patients (9.1%), but in 6 of them RRT was employed in the final stages of multi-organ failure. The incidence of AKI in severe burn patients is high according to the RIFLE or AKIN criteria and these patients experience more complications and higher mortality. Our study suggests that the use of HES in low doses in the burn resuscitation phase does not cause more AKI than resuscitation without HES, but further evaluation is required. Further studies should be conducted.

La souffrance rénale aiguë (SRA) est une complication sévère des patients brûlés. Il a récemment été recommandé d'éviter les HydroxyEthylAmidons (HEA) chez les patients brûlés en raison de l'augmentation de l'incidence des SRA. Le but de ce travail est d'évaluer l'incidence de la SRA chez des patients réanimés avec du Ringer Lactate et des HEA. Il s'agit d'une étude observationnelle conduite auprès de 165 patients admis en réanimation pour brûlés (surface 30 +/-15%). Les principaux paramètre recueillis étaient la SRA, les cristalloïdes et colloïdes utilisés, les scores de gravité, les comorbidités, les complications et la mortalité. Selon la classification de Rifle, 10 (6,1%) patients étaient dans le groupe à risque, 11 (6,7%) avaient une souffrance rénale et 11 (6,7%) une insuffisance rénale. Selon les critères AKIN, 9,7% des patients étaient au stade 1, 3% au stade 2 et 10,3% au stade 3. Une épuration extra-rénale a été nécessaire à 15 (9,1%) patients, 6 d'entre eux étant à un stade avancé de défaillance multiviscérale. Basée sur les scores Rifle comme AKIN, l'incidence de souffrance rénale est élevée chez les brûlés et ceux qui en souffrent ont une morbidité et une mortalité plus élevées. Toutefois, notre étude laisse à penser que les patients ayant reçu des HEA n'ont pas plus de souffrance rénale que ceux n'en ayant pas reçu, des études plus poussées restant nécessaires.

Optimal excitation and emission wavelengths to analyze amino acids and optimize neurotransmitters quantification using precolumn OPA-derivatization by HPLC.

We describe an analytical methodology to obtain high sensitivity and better resolution through the study of fluorometric excitation (λex) and emission (λem) spectrum wavelengths of OPA-amino acids. The spectrum emission study revealed a maximum signal peak at 450 nm for aspartate and glutamine. For glycine, taurine, and GABA, the maximum signal peak was at 448 and for glutamate at 452 nm. The remaining amino acids analyzed showed a maximum emission around 450 nm. The best signal obtained within the spectrum excitation experiments was using 229- to 450-nm λex-λem. The drawbacks observed at these wavelengths were a baseline drift and negative peaks occurrence. Thus, the excitation wavelength of 240 nm was chosen (240- to 450-nm λex-λem) as a compromise between a very good signal response and a baseline stability to resolve the 18 amino acids studied. Furthermore, this protocol was properly validated. On the other hand, the elution gradient program used for neuroactive amino acids (aspartate, glutamate, glycine, taurine and GABA) showed separation to the baseline, in a 15-min run in all of them. Other amino acids, up to 18, also exhibited a very good separation in a 25-min run. In conclusion, we propose the use of 240- to 450-nm λex-λem wavelengths, in OPA-amino acids analysis, as the most suitable protocol to obtain the best signal response, maintaining an optimum chromatographic resolution.

Comparison of fluid compartments and fluid responsiveness in septic and non-septic patients.

Our objective was to study the response to a fluid load in patients with and without septic shock, the relationship between the response and baseline fluid distributions and the ratios of the various compartments. A total of 18 patients with septic shock and 14 control patients without pathologies that increase capillary permeability were evaluated prospectively. We used transpulmonary thermodilution to measure the extravascular lung water index, intrathoracic blood volume index and pulmonary blood volume. For the measurement of the initial distribution volume of glucose, plasma volume and extracellular water we used dilutions of glucose, indocyanine green and sinistrin respectively. Transpulmonary thermodilution and dilutions of glucose were repeated 75 minutes after the beginning of the fluid load. The patients in the septic group had higher volumes of extracellular water (median 295 vs. 234 ml/kg, P < 0.001), lower intrathoracic blood volume index (median 894 vs. 1157 ml/m2, P < 0.003), higher pulmonary permeability ratios (extravascular lung water/pulmonary blood volume) (P < 0.003) and higher systemic permeability ratios (interstitial/plasma volume) (P < 0.04). The intrathoracic blood volume index increase after fluid loading was lower in the septic group (10 vs. 145 ml/m2). The pulmonary permeability ratios did not correlate with the systemic permeability ratios, and in the septic group, the percentage volume retained in the intrathoracic blood volumes after fluid loading did not correlate with the systemic permeability ratios. Septic shock can cause a redistribution of fluids. Fluid administration in these patients produced a minimal increase in intrathoracic blood volume, and the percentage of volume retained in this space was not correlated with the interstitial/plasma volume ratio.

The TLR1/2 agonist PAM(3)CSK(4) instructs commitment of human hematopoietic stem cells to a myeloid cell fate.

Toll-like receptors (TLRs) constitute a family of nonpolymorphic receptors that are devoted to pathogen recognition. In this work, we have explored the impact of TLR ligands (TLR-L) on human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We show that HSCs and HPCs have a comparable pattern of expression of TLR transcripts characterized by the predominance of TLR1, -2, -3, -4 and -6. In long-term cultures of HSCs, HPCs and stromal cells, most TLR-L profoundly inhibited B-cell development while preserving or enhancing the production of myeloid cells. In short-term cultures, the TLR1/2 ligand PAM(3)CSK(4) induced a large proportion of HPCs to express markers of the myelomonocytic lineage. PAM(3)CSK(4) induced only marginal expression of myeloid lineage markers on HSCs but promoted their myeloid commitment as revealed by their acquisition of the phenotype of multi- and bipotential myeloid progenitors and by upregulation of the transcription factors PU.1, C/EBPalpha and GATA-1. Our results suggest that TLR agonists can bias the lineage commitment of human HSCs and shift the differentiation of lineage-committed progenitors to favor myelopoiesis at the expense of lymphoid B-cell development.

Meningioma intrapulmonar. Descripción de un caso y breve revisión de la literatura / Intrapulmonary meningioma

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Sarcoidosis torácica. Nuestra experiencia: análisis de 26 casos / Thoracic sarcoidosis. Our experience: analysis of 26 cases

Objetivos: Describir el perfil clínico biológico de la sarcoidosis torácica en nuestro medio.Material y métodos: Búsqueda restrospectiva de casos sarcoidosis, desde enero/1998 hasta octubre/2004, a través del programa informático (DOCtor) de nuestro Hospital. Se contrastó con los registros de Anatomía Patológica que mostraran granulomas. Se excluyeron aquellos pacientes sin diagnóstico confirmado histológicamente a excepción del sd Lofgren,y los casos de sarcoidosis que no tuvieran afectación torácica.Resultados: De un total de 41 casos encontrados tras la explotación de datos se excluyeron 10 pacientes por no cumplir los criterios diagnósticos, y otros 5 por no presentar afectación torácica. La incidencia anual de los 26 casos de sarcoidosis torácica fue 1,48/100.000 habitantes. La distribución por sexos fue 14 mujeres (53,85%), edad media 41 años (27-76). Sólo 2 casos estaban asintomáticos (7,7%). Ningún paciente presentó afectación de más de 3 órganos. El estadioradiológico I por TAC fue el predominante (53,84%), y no hubo ningún caso de estadio III, IV; 4 casos tenían Rx tórax simple normal. Presentaban alteración ventilatoria restrictiva ligera con difusión normal sólo 2 (8,7%) , que corresponde a 18.18% de los casos con estadio II, ninguno presentaba afectación gasométrica significativa. La mediastinoscopia fue el método diagnóstico que lo consiguió en la mitad de los casos. La rentabilidad de la biopsia transbronquial global fue del 31%, pero en estadio II del 57%. De todos los casos los pacientes tratados fueron 8 (30,76%), con indicación correctaen el 50% casos. En el seguimiento se objetivaron 6 remisiones espontáneas, 6 casos perdidos (23%); en el momento actual no han completado seguimiento a 3 años desde el diagnóstico 13 casos.Conclusiones: La sarcoidosis torácica no es tan infrecuente en nuestro medio. El perfil clínico-biológico es similar aldescrito en la literatura, excepto en la distribución por sexos y el bajo número de pacientes asintomáticos. La realización de fibrobroncoscopia creemos debe incluirse entre las herramientas diagnósticas para confirmación histológica. La estadificación debemos intentar realizarla mediante TAC-AR por su mayor sensibilidad y especificidad que Rx tórax simple;y se debe completar con estudios de función pulmonar y búsqueda de manifestaciones extratorácicas por órganos

Objectives: Describe the biological clinical profile of thoracic sarcoidosis in our setting.Material and methods: Retrospective search for sarcoidosis cases, from January 1998 to October 2004, with the computer program (DOCtor) of our hospital Fundación Alcorcón. It was compared with the pathology registries that show granulomas. Those patients without histologically confirmed diagnosis, except for Lofgren syndrome, and the cases of sarcoidosis that did not have thoracic involvement were excluded.Results: Ten patients out of a total of 41 cases found after the data processing were excluded as they did not fulfill diagnostic criteria and 5 others because they had no thoracic involvement. Annual incidence of the 26 cases of thoracic sarcoidosis was 1.48/100,000 inhabitants. Distribution by gender was 14 women (53.85%), mean age 41 years (27-76). Only 2 cases were asymptomatic (7.7%). No patient had more than 3 organs affected. Radiology stage I by CT scan was predominant (53.84%), and there were no cases of stage III, IV; 4 cases had normal plain chest X-ray. Only 2 (8.7%)had mild restrictive ventilatory alteration with normal diffusion, that corresponded to 18.18% of the cases with stage II. None had significant gasometric involvement. The mediastinocopy was the diagnostic method that achieved it in half of the cases. Profitability of the global transbronchial biopsy was 31% but that of stage II was 57%. Of all the cases, 8 patients (30.76%) were treated, with correct indication in 50% of the cases. In the follow-up, 6 spontaneous remissions,6 lost cases (23%) were seen. At present 13 cases have not completed follow-up at 3 years from diagnosis.Conclusions: Thoracic sarcoidosis is not so rare in our setting. The clinical-biological profile is similar to that described in the literature, except in the distribution by gender and the low number of asymptomatic patients. We believe thatperforming the fibrobronchoscopy should be included among the diagnostic tools for histological confirmation. We should try to do the staging with the high resolution CT scan because it has greater sensitivity and specificity than the plain Xrayand should be completed with pulmonary function studies and search for extrathoracic manifestations by organs

A study of risk factors for hypospadias in the Rhône-Alpes region (France).

OBJECTIVE: Hypospadias is one of the most common congenital urogenital malformations in males with a significantly increasing incidence over the past 20 years. The causes of this insufficient virilization of the genital tubercle are essentially unknown. SUBJECTS AND METHODS: A hospital-based controlled study was realized with 225 hypospadias cases at Debrousse Hospital, Lyon, using a detailed questionnaire completed during a consultation with the patients' parents and those of controls of the same age. The chi(2), the P-value, the odds ratios and the 95% confidence interval were assessed. RESULTS: Hypospadias was found to be positively associated with genetic factors (as defined by the presence of other case(s) in the family in one case in four) and with neonatal low birth weight, fair-haired boys, maternal history such as viral infection during the first trimester, order of parity, toxaemia of pregnancy, delivery modality such as caesarean section, and environmental pollution. CONCLUSIONS: These results show that aetiological factors of hypospadias are likely to be related to three main fields which interact: genes, the placenta and environmental factors.

Prevalence of diabetes and impaired glucose tolerance in Aragón, Spain.

OBJECTIVE: To determine the prevalence of diabetes and impaired glucose tolerance (IGT) and to investigate their associated cardiovascular risk factors in Aragón, Spain. RESEARCH DESIGN AND METHODS: We performed a population-based cross-sectional study with stratified and purposive sampling of residents aged 10-74 years. A sample of 935 subjects (427 men and 508 women) was selected. All except those with a previous history of diabetes underwent an oral glucose tolerance test (OGTT), and World Health Organization (WHO) criteria were used for diagnosis of undiagnosed diabetes and IGT. Plasma lipid levels, blood pressure, BMI, and waist-to-hip ratio were also measured. RESULTS: The prevalence of diagnosed and undiagnosed diabetes and IGT was 3.1, 3.0, and 7.2%, respectively. In the age range of 30-64 years, the age-adjusted prevalence of diabetes (using the world population of Segi) was 7.1% in men and 5.6% in women. Both diabetes and IGT were associated with high blood pressure, high triglyceride levels, low HDL cholesterol levels, and overweight and upper-body fat distribution. Only upper-body fat distribution in women was significantly higher in subjects with diabetes than in subjects with IGT. CONCLUSIONS: The prevalence of diabetes in Aragón was moderately high (6.1%) and comparable with that reported in other white populations around the world. The proportion of unknown cases of diabetes was nearly 50%. Cardiovascular risk factors associated with diabetes and IGT supported the existence of an insulin resistance or metabolic syndrome, but there were not sufficient differences between diabetes and IGT to suggest a possible pathogenetic relation of hyperinsulinemia and associated risk factors.