Disease disclosure, treatment adherence, and behavioural profile in a cohort of vertically acquired HIV-infected adolescents. NeuroCoRISpeS study.

UNLABELLED: Advances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening. RESULTS: A total of 95 patients (58% women) were assessed with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7 years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132-998), with 34% (10-52%). Viral load was <50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038). CONCLUSION: Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

Lipid and glucose alterations in perinatally-acquired HIV-infected adolescents and young adults.

BACKGROUND: Successful antiretroviral therapy (ART) has dramatically reduced mortality among HIV-infected children. However, there is growing concern about long-term effects associated to ART. The aim of this study was to determine the prevalence of metabolic abnormalities in a cohort of perinatally HIV-infected adolescents and young adults and to identify associated factors. METHODS: We present results from a cross-sectional analysis including individuals 12 to 20 years of age, from a prospective, longitudinal cohort of perinatally-acquired HIV-infected children, adolescents and young adults in Madrid. Clinical and immunological data were recorded and complete lipid and glycemic profiles were determined. RESULTS: Ninety-nine adolescents were included, with a median age of 15.3 years [13.6-16.7]. Patients with abnormal levels of lipids were as follows: 27.2% total cholesterol ≥200 mg/dl, 25.9% LDL cholesterol (LDL-c) ≥ 130 mg/dl, 14.1% HDL-C < 35 mg/dl and 39.8% triglycerides ≥ 150 mg/dl. Current use of protease inhibitors (PI) was associated with higher triglyceride values (p = 0.022). Four (4.6%) patients showed fasting glucose ≥ 100 mg/dl and 30.6% presented with insulin resistance (IR) (HOMA-IR over the 90th centile). In the multivariate logistic regression analysis adjusted for sex, age, weight, Tanner stage, protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) treatment length and CD4 nadir, IR was associated with higher waist circumference Z score; OR: 3.92(CI95%: 1.15-13.4) (p = 0.03). CONCLUSION: There was a high prevalence of insulin resistance and lipid abnormalities in this cohort of perinatally-acquired HIV-infected adolescents. A simple clinical measurement like waist circumference Z score might be a reliable marker and predictor of insulin resistance in these patients.

Blood lead levels, δ-ALAD inhibition, and hemoglobin content in blood of giant toad (Rhinella marina) to assess lead exposure in three areas surrounding an industrial complex in Coatzacoalcos, Veracruz, Mexico.

The Coatzacoalcos Region in Veracruz, Mexico houses one of the most important industrial complexes in Mexico and Latin America. Lead is an ubiquitous environmental pollutant which represents a great risk to human health and ecosystems. Amphibian populations have been recognized as biomonitors of changes in environmental conditions. The purpose of this research is to measure exposure to lead and evaluate hematological and biochemical effects in specimens of giant toads (Rhinella marina) taken from three areas surrounding an industrial complex in the Coatzacoalcos River downstream. Lead levels in toads' blood are between 10.8 and 70.6 µg/dL and are significantly higher in industrial sites. We have found a significant decrease in the delta-aminolevulinic acid dehydratase (δ-ALAD) activity in blood from 35.3 to 78 % for the urban-industrial and industrial sites, respectively. In addition, we have identified a strong inverse relationship between the δ-ALAD activity and the blood lead levels (r = -0.84, p < 0.001). Hemoglobin and mean corpuscular hemoglobin levels, as well as the condition factor, are found to be lower at industrial sites compared with the reference sites. Our results suggest that the R. marina can be considered a good biomonitor of the δ-ALAD activity inhibition and hematological alterations at low lead concentrations.

Exposure to persistent organic pollutants (POPs) and DNA damage as an indicator of environmental stress in fish of different feeding habits of Coatzacoalcos, Veracruz, Mexico.

The region of Coatzacoalcos, Veracruz hosts one of the largest and most important industrial areas of Mexico and Latin America. Industrial development and rapid population growth, have triggered a severe impact on aquatic ecosystems of the region. The aim of this study was to determine the levels of POPs in sediment and in muscle tissue of five fish species from different trophic levels in downstream residents of the Coatzacoalcos River, and their integration with DNA damage in the fish, evaluated with the comet assay in whole blood as a biological indicator of stress, in order to obtain a baseline of the ecological condition of the region. The compounds detected in sediment and in muscle tissue were hexachlorobenzene (HCB), α-, ß-, γ-hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), mirex and polychlorinated biphenyls (PCBs). Sediment concentrations of these pollutants (except for mirex) exceeded the values of protection provided by international guidelines, suggesting a potential risk to aquatic life in the region. DNA damage recorded in the fish species is evidence of exposure to a mix of genotoxic pollutants, which combined with exposure to POPs, reflects the degree of environmental stress of aquatic organisms in the region. The results of this study show the importance of determining the presence of contaminants in the environment, the bioaccumulation in tissues and their effects on exposed organisms, providing an integrated approach in assessing the health of aquatic ecosystems.

Wild rodents (Dipodomys merriami) used as biomonitors in contaminated mining sites.

Mining is one of the most important industrial activities globally; however, mining processes have critical environmental impacts, as mining is a major source of metals and metalloids that contribute significantly to the pollution of soil, sediment, water and air. Heavy metals can impact the health of exposed human populations and nonhuman receptors. This study focused on arsenic because its genotoxicity is well-known. Previously, we proposed a methodology to evaluate and integrate risk from a single source affecting different biologic receptors. Here, we propose an alternative approach estimating arsenic exposure in children and kangaroo rats using probabilistic simulation with Monte Carlo modeling. The estimates are then associated to measured DNA damage and compared to both populations of children and rodents living in contaminated and in reference areas. Finally, based on the integrated analysis of the generated information, we evaluate the potential use of wild rodents (Dipodomys merriami) as a biomonitor at mining sites. Results indicate that the variation of genotoxicity in children of the reference site is approximately 2 units when compared to the children of the contaminated site. In the rodents we observed a variation of approximately 4 units between those of the reference site when compared to those living on the contaminated site. We propose that D. merriami can be used as a biomonitor organism in sites with mining activity, and that a non-lethal test can be used to evaluate risk from metal exposure.

DNA damage in earthworms (Eisenia spp.) as an indicator of environmental stress in the industrial zone of Coatzacoalcos, Veracruz, Mexico.

Coatzacoalcos, Veracruz is one of the major industrial areas of Mexico. Presently, the Coatzacoalcos River and the areas surrounding the industrial complex are considered by various authors to be some of most polluted sites in Mexico. The objective of this study was to determine if earthworms could be used as indicators of environmental stress in the Coatzacoalcos industrial zone. Often, detritivores and decomposers such as earthworms are the first to be affected when the soil is contaminated. We collected soil samples to be used for persistent organic pollutants (POPs) quantification by gas chromatography. Concentrations of hexachlorobenzene, lindane and total polychlorinated biphenyls (PCBs) in the soil were above the maximum permissible limits of the Canadian Environmental Quality Guidelines (CEQG). Comet assay was conducted in coelomocytes of wild earthworms collected in Coatzacoalcos and compared with the control earthworms. We found DNA damage in earthworms from Coatzacoalcos that was significantly higher (P < 0.05) in comparison to laboratory earthworms. Earthworms are an appropriate organism to use as an indicator of environmental impact in contaminated sites. DNA damage recorded in the earthworms provides clear evidence of environmental impacts by the chemical industry on the wildlife of this region.

Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice.

The glutamatergic system has emerged as a novel pathway for treating major depressive disorder (MDD) with the focus on producing both rapid and sustained antidepressant effects. Dextromethorphan is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that has produced antidepressant-like effects in forced swim and tail suspension tests (TST); however, the rapid and sustained antidepressant-like effects of dextromethorphan have not been evaluated. This study evaluated the rapid and sustained (24 h) antidepressant-like effects of dextromethorphan (0-32 mg/kg) in C56BL/6 mice using the novelty-induced hypophagia (NIH) test and TST, respectively. Additionally, we evaluated anxiety-related behavior and locomotor effects of dextromethorphan (0-56.0 mg/kg) using the light-dark and open field tests. Dextromethorphan (32 mg/kg) produced acute (30 min) antidepressant-like effects in TST, but failed to produce antidepressant-like effects 24 h after drug administration. Treatment of dextromethorphan (32 mg/kg) alone or in combination with CYP2D6 enzyme inhibitor Quinidine (32 mg/kg) failed to produce rapid antidepressant-like effects by increasing the latency to drink in the NIH test rather than decreasing the latency to drink. Dextromethorphan (56 mg/kg) produced an anxiogenic-like effect by decreasing the time spent in the light side, number of entries, and latency to enter the light side in the light-dark test. Administration of dextromethorphan (0-56 mg/kg) did not significantly alter locomotor activity. Although dextromethorphan is considered a noncompetitive NMDA receptor antagonist, dextromethorphan binds to several monoaminergic receptors (SERT and NET) and likely produces the antidepressant-like effects through these receptors similar to traditional antidepressant drugs. Additionally, these results suggest that the therapeutic window for dextromethorphan in the clinical population is small as similar doses produce antidepressant-like and anxiogenic-like behaviors.

Determination of lead in samples of zooplankton, water, and sediments in a Mexican reservoir: evidence for lead biomagnification in lower/intermediate trophic levels?

We have determined lead concentration of water, sediment, and zooplankton samples of El Niágara, a reservoir in Aguascalientes, Mexico. Our results include the first report of bioconcentration factor (BCF) obtained in an actual ecosystem (as opposed to the experimental setups in the laboratory) for a rotifer species; Asplanchna brigthwellii (BCF ca. 49 300). The BCF of this predatory zooplanktonic species (A. brigthwellii) are up to four times greater than those of two grazing zooplanktonic species (Daphnia similis and Moina micrura). In this contaminated reservoir that lacks fishes, Asplanchna, and Culex sp. together with ducks and other bigger invertebrates might represent the top predators. Our data suggest that biomagnification of lead through at least one trophic level can occur in freshwater systems. Biomagnification in A. brigthwellii might be explained in part by predation of this voracious predator on young of the herbivorous cladoceran, M. micrura. Our findings stand opposite to the current theoretical framework where lead biomagnification occurs only in lower trophic levels.

[Effect of a four-week vitamin and mineral supplementation on the nutritional status and urinary excretion of arsenic in adolescents]. / Efecto de una suplementación de vitaminas y minerales de cuatro semanas sobre el estado nutricio y excreción urinaria de arsénico en adolescentes.

INTRODUCTION: adequate nutrition in adolescence is important for growth and development. There are environmental factors that cannot be avoided, such as exposure to heavy metals through natural sources such as water. Arsenic is a metalloid that can cause damage to health (alterations in nutritional status, diabetes, cancer) and it has been found in concentrations higher than those allowed in drinking water. OBJECTIVE: to measure the effect of vitamin and mineral supplementation on the nutritional status and urinary excretion of arsenic in adolescents exposed to this metal through drinking water. MATERIAL AND METHODS: an observational, follow-up study of a cohort was conducted to assess the efficacy of vitamin and mineral supplementation on supplementation in 45 adolescents exposed to arsenic in drinking water, who were given a daily multivitamin supplement for four weeks. Weekly nutritional status and arsenic levels in urine and drinking water were evaluated. RESULTS: the basal nutritional intake was low for proteins, fiber, folic acid, vitamin B2, B6, B12, E, C, selenium and iron, increasing their consumption through the supplement during the intervention and with an increase of approximately 1 g/dl of hemoglobin in all participants. At the end of the intervention, there was an increase in fat-free mass and a decrease in the percentage of body fat. In relation to the urinary excretion of arsenic, the biggest elimination of this metalloid was observed from the first week of intervention (35.91 µg/g Cr [IC 95% = 23.2-74.8 µg/g Cr]), which was statistically significant compared to basal levels of urinary arsenic (43.2 µg/g Cr [IC 95% = 30.8-117.6 µg/g Cr]) (p < 0.05), with an average water consumption with As of 96.2 ± 7.5 µg/l. CONCLUSION: four weeks of supplementation with vitamins and minerals in the adolescent population studied improved nutritional status and increased metalloid excretion significantly in the first and second week after intervention.

Introducción: la adecuada nutrición en la adolescencia es de importancia para el crecimiento y desarrollo. Existen factores ambientales que no pueden evitarse, como la exposición a metales pesados a través de fuentes naturales como el agua. El arsénico es un metaloide que puede causar un daño a la salud (alteraciones del estado nutricio, diabetes, cáncer) y ha sido encontrado en concentraciones superiores a las permitidas en el agua de consumo.Objetivo: medir el efecto de una suplementación de vitaminas y minerales sobre el estado nutricio y la excreción urinaria de arsénico en adolescentes expuestos a este metal a través de agua de consumo.Material y métodos: se realizó un estudio de intervención y longitudinal para la valorar la eficacia de la suplementación de vitaminas y minerales sobre la suplementación en 45 adolescentes, expuestos a arsénico en agua de consumo, a quienes se dio un suplemento multivitamínico diariamente durante cuatro semanas. De forma semanal se evaluaron el estado nutricio y los niveles de arsénico en orina y en agua de consumo.Resultados: en la población de estudio se observó que el consumo nutrimental basal fue bajo para proteínas, fibra, ácido fólico, vitamina B2, B6, B12, E, C, selenio y hierro, incrementando su consumo a través del suplemento durante la intervención y con un aumento de aproximadamente 1 g/dl de hemoglobina en todos los participantes. Al final de la intervención presentaron incremento de masa libre de grasa y disminución en el porcentaje de grasa corporal. Por otro lado, en cuanto a la excreción urinaria de arsénico, se observó mayor eliminación de este metal (35,91 µg/g Cr [IC 95% = 23,2-74,8 µg/g Cr]) desde la primera semana de intervención, la cual fue estadísticamente significativa en comparación con los niveles basales de arsénico urinario (43,2 µg/g Cr [IC 95% = 30,8-117,6 µg/g Cr]) (p < 0,05), con un consumo promedio de agua con As de 96,2 ± 7,5 µg/l.Conclusión: la suplementación con vitaminas y minerales de cuatro semanas en la población de adolescentes estudiada mejoró el estado nutricio y aumentó la excreción del metaloide de manera significativa en la primera y segunda semana postintervención.

Collagenase 1A2 (COL1A2) gene A/C polymorphism in relation to severity of dental fluorosis.

OBJECTIVES: The aim of this study was to evaluate the putative association between the presence of the COL1A2 gene A/C polymorphism and the severity of dental fluorosis in a sample exposed to high concentrations of fluoride. METHODS: A cross-sectional study was carried out that included 80 children residing in a community with high concentrations of fluoride in the drinking water. To determine whether the presence of this polymorphism and dental fluorosis are associated, the presence of the dental fluorosis was considered to be a response variable, while fluoride concentration in water and urine was designated as independent variables. In addition, the children's parents completed questionnaires with general information about drinking and cooking with tap water, consumption of milk and soft drinks, and other putative risk factors. RESULTS: Individuals with the polymorphism had nonsignificant odds (OR = 2.24; 95% CI = 0.55-9.02) of having dental fluorosis at higher exposures to fluoride. This finding was similar in individuals without the polymorphism (OR = 1.65; 95% CI = 0.44-6.17). CONCLUSIONS: The presence of polymorphism in the COL1A2 gene was not associated with the severity of dental fluorosis.

Effect of coexposure to DDT and manganese on freshwater invertebrates: pore water from contaminated rivers and laboratory studies.

An environmental survey of several rivers of the southern Huasteca area of Mexico revealed high concentrations of manganese (Mn) and the presence of DDT in the sediments and pore water. Therefore, acute (48-h) toxicities of Mn and DDT were assessed both independently and as a combination on 24-h-old neonates of Daphnia magna Strauss and Lecane quadridentata Ehrenberg. Daphnia magna showed high sensitivity to both toxicants, whereas L. quadridentata was highly resistant to DDT and less susceptible to Mn. For D. magna, the Mn and DDT coexposure was significantly more toxic than any of the singly tested compounds. When D. magna was exposed to sediment pore water, no association was found between the Mn content in the samples and the observed toxicity. Preliminary particle analysis of pore water showed different compounds of Mn, which apparently were not in bioavailable form.

Effect of mining activities in biotic communities of Villa de la Paz, San Luis Potosi, Mexico.

Mining is one of the most important industrial activities worldwide. During its different stages numerous impacts are generated to the environment. The activities in the region have generated a great amount of mining residues, which have caused severe pollution and health effects in both human population and biotic components. The aim of this paper was to assess the impact of mining activities on biotic communities within the district of Villa de la Paz. The results showed that the concentrations of As and Pb in soil were higher than the national regulations for urban or agricultural areas. The bioavailability of these metals was certified by the presence of them in the roots of species of plants and in kidneys and livers of wild rodents. In regard to the community analysis, the sites that were located close to the mining district of Villa de la Paz registered a lower biological diversity, in both plants and wild rodents, aside from showing a change in the species composition of plant communities. The results of this study are evidence of the impact of mining on biotic communities, and the need to take into account the wildlife in the assessment of contaminated sites.

Infrautilización de la anticoagulación oral en el paciente octogenario con fibrilación auricular: perspectiva desde la práctica clínica real / Underuse of oral anticoagulation in octogenarian patient with atrial fibrillation: a perspective from real clinical practice

Introducción y objetivos: La fibrilación auricular es la arritmia más frecuente en los pacientes ancianos. La decisión de la anticoagulación en este grupo puede ser difícil. Quisimos estudiar el manejo de la anticoagulación oral en pacientes muy mayores con fibrilación auricular en la práctica clínica real y los factores asociados con la decisión de anticoagular. Métodos: Estudiamos todos los pacientes mayores de 80 años de edad, con fibrilación auricular conocida atendidos en la consulta de geriatría de junio a diciembre de 2013. Resultados: Estudiamos 90 pacientes, con edad media de 85,6 años. La media de la puntuación de CHA2DS2-VASc fue de 4,7 y la media de HAS-BLED fue de 2. El 53% estaban anticoagulados. De los pacientes anticoagulados, el 96% tomaban acenocumarol y un 4% los nuevos anticoagulantes. En el análisis multivariante, la edad y el antecedente de demencia se asoció a la decisión de no anticoagulación. Conclusiones: Según nuestros resultados, un alto porcentaje de pacientes muy mayores con fibrilación auricular están sin anticoagular. El antecedente de demencia y la edad pesan más que la puntuación CHAD2DS2-Vasc y HAS-BLED a la hora de decidir la anticoagulación.

Introduction and objectives: Atrial fibrillation is the most common arrhythmia in elderly patients. Anticoagulation decision in this group can be difficult. We wanted to study the management of oral anticoagulation in very elderly patients with atrial fibrillation in clinical practice and the factors associated with the decision to anticoagulation. Methods: We studied all patients older than 80 years with known atrial fibrillation treated at the geriatric consultation from June to December 2013. Results: We studied 90 patients with a mean age of 85.6 years. The mean score of CHA2DS2-VASc was 4.7 and the mean of HAS-BLED was 2. 53% were anticoagulated. Out of anticoagulated patients, 96% were taking Acenocumarol and 4% new anticoagulants. In multivariate analysis, age and history of dementia was associated with the decision not to use anticoagulants. Conclusions: Our results suggest that a high percentage of very elderly patients with atrial fibrillation are without anticoagulation. The history of dementia and age outweigh the CHAD2DS2-Vasc and HAS-BLED score on deciding to anticoagulate.

A case report of a pyogenic liver abscess caused by Fusobacterium nucleatum in a patient with autosomal dominant polycystic kidney disease undergoing hemodialysis.

Pyogenic liver abscess (PLA) is a process with significant morbidity and mortality and is a rare complication in an aisled way in patients with autosomal dominant polycystic kidney disease (ADPKD). In addition to hepatic cyst infection, intracystic hemorrhage is another complication seen in ADPKD patients; however, the liver parenchyma itself remains normal. A PLA located in normal liver tissue in these kinds of patients has not been previously reported. Fusobacterium nucleatum is an anaerobic bacterium with rare involvement other than in periodontal infections. A 58-year-old Caucasian male, who was on hemodialysis treatment from July 2004 due to end-stage renal disease secondary to ADPKD, was admitted with fever, rigor, chills, weakness, and abdominal pain of 10 days duration. During that time, ciprofloxacin 500 mg, twice daily, gentamycin 80 mg/48 h, and vancomycin 1 g/week, were prescribed, but treatment was interrupted by hospitalization. Physical examination on admission revealed that the patient had a fever of 39.8 degrees C, pallor, chills, right upper quadrant abdominal pain, and hepatosplenomegaly. Abdominal ultrasound revealed a 5.3 cm diameter collection with irregular configuration located in the caudate lobe. Abdominal computed tomography (CT) showed a large multiloculated hepatic collection. The PLA was managed with antibiotics (metronidazole) and continuous catheter drainage (8Fr drainage catheters [Abocath-T, Abbott, Sligo, Ireland]) into the abscess. Fluid culture was positive for F. nucleatum. Complete remission was obtained after 12 days without complications. We describe a PLA by F. nucleatum, in a very rare location in an ADPKD patient undergoing hemodialysis without complicated cysts, managed with antibiotics and percutaneous drainage with satisfactory resolution.

An integrated health risk assessment approach to the study of mining sites contaminated with arsenic and lead.

In order to test the value of an integrated approach for the analysis of health risks at contaminated sites, an integrated health risk assessment in a mining area was performed following 3 steps: 1) Environmental monitoring of surface soil, 2) assessment of exposure to metals in children and native rodents, and 3) DNA damage evaluation (comet assay) in children and rodents. These aspects also were studied in less exposed populations. Our results in humans showed that children living in the most polluted area (Villa de la Paz, Mexico) had higher lead blood concentrations (geometric mean of 13.8 microg/dL) and urinary arsenic levels (geometric mean of 52.1 microg/g creatinine) compared to children living in a control area (Matehuala, Mexico; blood lead of 7.3 microg/dL; urinary arsenic of 16.8 microg/g creatinine). Furthermore, the exposed children also had increased DNA damage (tail moment mean in Villa de la Paz of 4.8 vs 3.9 in Matehuala; p < 0.05). Results in rodents were identical. Animals captured in the polluted area had higher levels of arsenic (geometric mean of 1.3 microg/g in liver and 1.8 microg/g in kidney), lead (0.2 microg/g in liver and 0.9 microg/g in kidney), and cadmium (0.8 microg/g in liver and 2.2 microg/g in kidney), and increased DNA damage (tail moment mean of 18.2) when compared to control animals (arsenic in liver of 0.08 microg/g and kidney of 0.1 microg/g; lead in liver of 0.06 microg/g and kidney of 0.3 microg/g; cadmium in liver of 0.06 microg/g and kidney of 0.6 microg/g; and tail moment of 14.2). With the data in children and rodents, the weight-of-evidence for health risks (in this case DNA damage) associated with metal exposure in Villa de la Paz was strengthened. Therefore, a remediation program was easier to justify, and a feasibility study at this site is under way.

Ultrapure dialysate and inflammatory response in haemodialysis evaluated by darbepoetin requirements--a randomized study.

BACKGROUND: Dialysate quality has been suggested to influence inflammation status in patients subject to haemodialysis (HD). The aim of this study was to compare ultrapure dialysate (UPD) vs conventional dialysate (CD) with respect to darbepoetin requirements and other inflammation markers. METHODS: A controlled prospective randomized study was carried out on 78 patients from two HD units who were treated with low-flux polyamide dialysers. Patients were assigned to two groups by using different sized blocks per unit and dialysis session. One group received CD treatment while the other was treated with UPD over 12 months. From the groups, 37 patients started treatment with CD and 41 with UPD while 31 patients ended with CD and 30 with UPD. The main variables analysed were haemoglobin (Hb) and darbepoetin dose; other variables studied were C-reactive protein (CRP), albumin, interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra). RESULTS: No significant differences were observed between the two groups for the variables analysed. At the beginning of the study the following values of CD and UPD were assessed: Hb 11.3 and 11.3 (g/dl); darbepoetin dose: 0.49 and 0.44 (microg/kg/week); CRP: 13 and 24 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 5.94 and 4.18; and IL-1Ra: 345 and 420 (ng/l), respectively. At the end of the study the values of CD and UPD were: Hb 12 and 11.9 (g/dl); darbepoetin dose: 0.47 and 0.48 (microg/kg/week); CRP: 14 and 14 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 14.03 and 12.93 and IL-1Ra: 322 and 340 (ng/l). CONCLUSIONS: UPD does not improve the inflammatory status evaluated by darbepoetin requirements in conventional HD patients treated with low-flux polyamide dialyser. Further controlled studies are required to evaluate the clinical influence of UPD in HD with other low- and high-flux membranes.

[Recommendations of the CEVIHP/SEIP/AEP/PNS on antiretroviral treatment in HIV-infected children and teenagers]. / Recomendaciones CEVIHP/SEIP/AEP/PNS respecto al tratamiento antirretroviral en niños y adolescentes infectados por el VIH.

OBJECTIVE: To update antiretroviral recommendations in antiretroviral therapy (ART) in HIV-infected children and adolescents. METHODS: Theses guidelines have been formulated by a panel of members of the Plan Nacional sobre el SIDA (PNS) and the Asociacion Espanola de Pediatria (AEP) by reviewing the current available evidence of efficacy, safety, and pharmacokinetics in pediatric studies. Three levels of evidence have been defined according to the source of data: Level A: randomized and controlled studies; Level B: Cohort and case-control studies; Level C: Descriptive studies and experts' opinion. RESULTS: When to start ART should be made on an individual basis, discussed with the family, considering the risk of progression according to age, CD4 and viral load, the ART-related complications and adherence. The ART goal is to reach a maximum and durable viral suppression. This is not always possible, even with clinical and immunologic improvement. The difficulties of permanent adherence and side-effects are resulting in a more conservative trend to initiate ART, and to less toxic and simpler strategies. Currently, combinations of at least three drugs are of first choice both in acute and chronic infection. They must include 2 NA 1 1 NN or 2 NA 1 1 PI. ART is recommended in all symptomatic patients and, with few exceptions, in all infants in the first year of life. Older asymptomatic children should start ART according to CD4 count, especially CD4 percentage, that vary with age. Despite potent salvage therapies, it is common not to reach viral undetectability. Therapeutical options when ART fails are scarce due to cross-resistance. The cause of failure must be identified. Occasionally, there exists clinical and/or immunological progression, and a change of therapy with at least two new drugs still active for the patient, is warranted with the aim of increasing the CD4 count to a lower level of risk. Toxicity and adherence must be regularly monitored. Some aspects about post exposure prophylaxis and coinfection with HCV or HBV are discussed. CONCLUSIONS: A higher level of evidence with regard to ART effectiveness and toxicity in pediatrics is currently available, leading to a more conservative and individualized approach. Clinical symptoms and CD4 count are the main determinants to start and change ART.

Garenoxacin (BMS-284756) and moxifloxacin in experimental meningitis caused by vancomycin-tolerant pneumococci.

The emergence of multidrug-resistant strains of Streptococcus pneumoniae drives the development and evaluation of new antipneumococcal agents, especially for the treatment of bacterial meningitis. The aims of the present study were to assess the antibacterial effectiveness of two new quinolones, garenoxacin (BMS; BMS-284756) and moxifloxacin (MOX) in experimental meningitis caused by a vancomycin (VAN)-tolerant S. pneumoniae strain and to compare the results with those obtained by therapy with VAN and ceftriaxone (CRO) in combination. Meningitis was induced in young male New Zealand White rabbits by intracisternal inoculation of a VAN-tolerant pneumococcal strain (strain Tupelo) from a child with meningitis. Sixteen hours after inoculation, therapy was given by intravenous administration of BMS at 20 mg/kg of body weight, followed 5 h later by administration at a dosage of 10 mg/kg (n = 9 animals) or MOX as two doses of 20 mg/kg every 5 h (n = 8 animals). For comparison, we studied the following groups: (i) animals treated with VAN (20 mg/kg every 5 h, three doses) and CRO (125 mg/kg, one dose) (n = 9), (ii) animals infected with a VAN-tolerant strain but not treated (n = 8), (iii) animals infected with a VAN-tolerant pneumococcus isolated from the nasopharynx of a carrier and treated with BMS (n = 8), and (iv) animals infected with a cephalosporin-resistant type 6B S. pneumoniae strain and treated with BMS (n = 6). The MICs of penicillin, CRO, VAN, BMS, and MOX for the Tupelo strain were 2, 1, 0.5, 0.06, and 0.03 micro g/ml, respectively. The rates of killing of strain Tupelo (the change in the log(10) number of CFU per milliliter per hour) in cerebrospinal fluid at 5 h were -0.70 +/- 0.35, -0.61 +/- 0.44, and -0.49 +/- 0.36 for BMS, MOX, and VAN-CRO, respectively. Therapy with BMS and MOX was as effective as therapy with VAN-CRO against VAN-tolerant pneumococcal meningitis in rabbits.

Revisión de las metodologías sobre evaluación de riesgos en salud para el estudio de comunidades vulnerables en América Latina / Health risk assessment methodologies for the study of vulnerable communities in Latin America / Revisão das metodologias sobre avaliação de riscos na saúde para o estudo de comunidades vulneráveis na América Latina

Los métodos para evaluar el riesgo en salud se basan, en general, en el monitoreo ambiental y en la estimación de la exposición a través de modelos matemáticos. La incertidumbre de tal estrategia es grande. En consecuencia, para incrementar la certidumbre sobre la evaluación de la exposición a los contaminantes, se ha propuesto el empleo de biomarcadores. No obstante, la complejidad de los nuevos escenarios de riesgo obliga a evaluar no solamente a las poblaciones humanas sino también al resto de la biota. Asimismo, factores ambientales, sociales y de salud, al afectar la vulnerabilidad, también deben ser considerados para la caracterización del riesgo. Estos factores de vulnerabilidad pueden evaluarse a través de indicadores. Al final, con los análisis ambientales, el uso de biomarcadores y el manejo de indicadores ambientales, sociales y de salud, puede evaluarse el riesgo de manera integrada (humanos y biota). En esta revisión se presentan las diversas estrategias empleadas por este grupo de trabajo para evaluar el riesgo en sitios contaminados, comunidades marginadas y en áreas afectadas por el cambio global climático.

The most commonly used methods for risk assessment are based on environmental analysis and the use of mathematical models for the estimation of exposure. However, the uncertainty of this approach is high, as the models are based on scenarios that may be not the correct ones. In order to decrease the uncertainty, the use of biomarkers has been proposed. Furthermore, considering the complexity of pollution in some sites, these biomarkers can be used both in humans and biota in order to obtain better information for the definition of risks at those sites. In addition to biomarkers, social, health and environmental indicators have to be applied for risk characterization, as different factors of vulnerability can modify the extent of health risks in some communities. At the end, with environmental monitoring and the use of biomarkers and indicators of vulnerability, health risks in humans and biota (integrated risk assessment) can be assessed in different scenarios. In this paper we present the strategies that our group developed for the study of hazardous waste sites, vulnerable communities and areas impacted by climate change.

Os métodos para avaliar o risco na saúde se baseiam, em geral, no monitoramento ambiental e na estimação da exposição através de modelos matemáticos. A incerteza de tal estratégia é grande. Em consequência, para incrementar a certeza sobre a avaliação da exposição aos contaminantes, tem sido proposta a utilização de biomarcadores. No entanto, a complexidade dos novos cenários de risco obriga a avaliar não somente as populações humanas mas também ao resto da biota. Da mesma forma, fatôres ambientais, sociais e de saúde, ao afetar a vulnerabilidade, também devem ser considerados para a caracterização do risco. Estes fatôres de vulnerabilidade podem avaliar-se através de indicadores. Finalmente, com as análises ambientais, o uso de biomarcadores e o manejo de indicadores ambientais, sociais e de saúde, pode-se avaliar o risco de maneira integrada (humanos e biota). Nesta revisão se apresentam as diversas estratégias empregadas por este grupo de trabalho para avaliar o risco em lugares contaminados, comunidades marginalizadas e em áreas afetadas pela mudança global climática.