Decoupling of biotic and abiotic patterns in a coastal area affected by chronic metal micronutrients disturbances.

Coastal systems are highly productive areas for primary productivity and ecosystem services and host a large number of human activities. Since industrialization, metal micronutrients in these regions have increased. Phytoplankton use metals as micronutrients in metabolic processes, but in excess, had deleterious effects. In coastal systems, picoeukaryotes represent a diverse and abundant group with widespread distribution and fundamental roles in biogeochemical cycling. We combined different approaches to explore picoeukaryotes seasonal variability in a chronically metal polluted coastal area at the south-eastern Pacific Ocean. Through remote and field measurements to monitor environmental conditions and 18S rRNA gene sequencing for taxonomic profiling, we determined metal chronic effect on picoeukaryote community's structure. Our results revealed a stable richness and a variable distribution of the relative abundance, despite the physicochemical seasonal variations. These results suggest that chronic metal contamination influences temporal heterogeneity of picoeukaryote communities, with a decoupling between abiotic and biotic patterns.

Detection of sentinel bacteria in mangrove sediments contaminated with heavy metals.

Mangroves in the Northwest Coast of South America are contaminated with heavy metals due to wastewater discharges from industries, affecting the biota from this environment. However, bacteria proliferate in these harsh environmental conditions becoming possible sentinel of these contaminations. In this study, bacterial community composition was analyzed by throughput sequencing of the 16S rRNA gene from polluted and pristine mangrove sediments affected by marked differences in heavy metal concentrations. Core bacteria were dominated by Proteobacteria, Firmicutes, and Bacteroidetes phyla, with strong differences between sites at class and genus levels, correlated with metal levels. Increment of abundance on specific OTUs were associated with either elevated or decreased concentrations of metals and with the sulfur cycle. The abundance of Sulfurovum lithotrophicum, Leptolinea tardivitalis, Desulfococcus multivorans and Aminobacterium colombiense increases when metals rise. On contrary, Bacillus stamsii, Nioella nitrareducens and Clostridiisalibacter paucivorans abundance increases when metal levels are reduced. We propose these OTUs as bacterial sentinels, whose abundance can help monitor the restoration programs of contaminated mangrove sediments in the future.

Función cognitiva en pacientes tratados con supresión androgénica: estudio prospectivo y multicéntrico / Cognitive function in patients on androgen suppression: A prospective, multicentric study

Objetivo: Evaluar el efecto de supresión androgénica sobre la función cognitiva de pacientes con cáncer de próstata (CP) tras 6 meses de tratamiento con análogos de la hormona liberadora de la hormona luteinizante. Material y métodos: Estudio prospectivo, observacional, multicéntrico y abierto de pacientes con CP programados para recibir análogos de la hormona liberadora de la hormona luteinizante durante ≥ 6 meses. Evaluamos 4 dominios de la función cognitiva antes del tratamiento y tras 6 meses: 1) memoria de trabajo: Escala Wechsler de inteligencia para adultos (WAIS III-dígito); 2) memoria visual: prueba de memoria visual; 3) capacidad vídeo-espacial: juicio de orientación de línea y rotación mental de objetos tridimensionales (rotación-3D); y 4) razonamiento analítico no verbal: WAIS III-MRT. Se consideraron mejorías o empeoramientos significativos cuando existió un cambio fuera del valor definido por el intervalo de confianza del 95% de la valoración basal de cada prueba. Resultados: De los 308 pacientes que completaron el estudio, en 245 (79,6%) no se observaron cambios significativos en ninguna prueba y en 63 pacientes (20,4%) se observaron cambios significativos en una prueba o más. De estos últimos la mayoría presentó un cambio en una sola prueba, distribuida uniformemente entre mejorías (58 pacientes; 18,8%) y empeoramientos (56; 18,2%). En la mayoría de pacientes (87,8-91,8%) no se observaron cambios significativos en las pruebas individuales respecto a sus niveles basales. El porcentaje de pacientes con cambios significativos (mejoría vs. deterioro, respectivamente) fue: WAIS III-dígito (6,3% vs. 5,9%); memoria visual (5,3% vs. 5,7%); juicio de orientación de línea (5,3% vs. 4,5%); rotación 3 D (4,1% vs. 4,1%); WAIS III-MRT (4,8% vs. 5,8%). Conclusiones: El estado cognitivo de los pacientes con CP no parece verse afectado por 6 meses de tratamiento con análogos de la LH

Objective: To assess the effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in patients with prostate cancer (PCa) after 6 months of treatment with luteinizing hormone-releasing hormone (LHRH) analogues. Material and methods: Prospective, observational, multicentre, open-label study of patients diagnosed with nonmetastatic or asymptomatic metastatic PCa scheduled to receive LHRH analogues for ≥ 6 months. We assessed four CP domains at baseline and after 6 months of ADT: 1) Working memory: Wechsler Adult Intelligence Scale III (WAIS III) Digit Span Subtest (WAIS III-Digit); 2) Visual memory: ad hoc visual memory test; 3) Visuospatial ability: Judgement of Line Orientation (JLO) and Mental Rotation of Three-Dimensional Objects (3D-Rotation); and 4) Nonverbal analytical reasoning: WAIS III Matrix Reasoning Test (WAIS III-MRT). Changes outside the baseline 95% confidence intervals were considered significant. Results: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test and 63 patients (20.4%) experienced significant changes in ≥1 test. Of these, most presented a change in only one test, distributed evenly between improvements (58 patients; 18.8%) and worsening (56 patients; 18.2%). For individual tests, most patients (87.8% to 91.8%) had no change from baseline; however, the significant changes (improvement vs. deterioration, respectively) were as follows: WAIS III-Digit (6.3% vs. 5.9%); visual memory (5.3% vs. 5.7%); JLO (5.3% vs. 4.5%); 3D-Rotation (4.1% vs. 4.1%); and WAIS III-MRT (4.8% vs. 5.8%). Conclusions: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration

Cognitive function in patients on androgen suppression: A prospective, multicentric study. / Función cognitiva en pacientes tratados con supresión androgénica: estudio prospectivo y multicéntrico.

OBJECTIVE: To assess the effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in patients with prostate cancer (PCa) after 6 months of treatment with luteinizing hormone-releasing hormone (LHRH) analogues. MATERIAL AND METHODS: Prospective, observational, multicentre, open-label study of patients diagnosed with nonmetastatic or asymptomatic metastatic PCa scheduled to receive LHRH analogues for≥6 months. We assessed four CP domains at baseline and after 6 months of ADT: 1) Working memory: Wechsler Adult Intelligence Scale III (WAIS III) Digit Span Subtest (WAIS III-Digit); 2) Visual memory: ad hoc visual memory test; 3) Visuospatial ability: Judgement of Line Orientation (JLO) and Mental Rotation of Three-Dimensional Objects (3D-Rotation); and 4) Nonverbal analytical reasoning: WAIS III Matrix Reasoning Test (WAIS III-MRT). Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test and 63 patients (20.4%) experienced significant changes in ≥1 test. Of these, most presented a change in only one test, distributed evenly between improvements (58 patients; 18.8%) and worsening (56 patients; 18.2%). For individual tests, most patients (87.8% to 91.8%) had no change from baseline; however, the significant changes (improvement vs. deterioration, respectively) were as follows: WAIS III-Digit (6.3% vs. 5.9%); visual memory (5.3% vs. 5.7%); JLO (5.3% vs. 4.5%); 3D-Rotation (4.1% vs. 4.1%); and WAIS III-MRT (4.8% vs. 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.

[Palliative care needs in the inmobilized population of a Primary Care area in Vigo Spain]. / Necesidad de cuidados paliativos en la población inmovilizada de un centro de salud de Vigo.

GENERAL OBJECTIVE: To determine palliative care needs in a sample of people with mobility problems in the area of the C.S. Matama by using the NECPAL instrument (identification and integral-integrated care of people with advanced chronic diseases in social and healthcare provision services). MATERIAL AND METHODS: Descriptive and cross-sectional study of patients immobilized in a health centre in Vigo (87 subjects overall). RESULTS: The average age of our patients is 84.34 years and 82% are women. The most frequent immobilization type was the patient's inability to leave their home (64%). The result of this test was positive in 38% of cases (33 patients), most of whom have chronic diseases and only 1 patient has been diagnosed with cancer. There is a significant negative association between the score obtained on the Barthel scale and the ratio of positives to the test. Concerning the use of resources there are important differences regarding hospital admissions and PHC depending on the outcome of the test. These differences were statistically significant with regard to PHC and emergency consultations. CONCLUSIONS: An immobilized patient is not synonymous with a patient in need of palliative care; the tool used has been proved to be useful to detect this need, which concerns a third of our patients. The results of the questionnaire of need for care palliative (NECPAL) relate well to the basic activities of daily living (Barthel scale score) and to indicators of use of health services.

Heavy metal concentration in mangrove surface sediments from the north-west coast of South America.

Mangrove ecosystems are coastal estuarine systems confined to the tropical and subtropical regions. The Estero Salado mangrove located in Guayaquil, Ecuador, has suffered constant disturbances during the past 20 years, due to industrial wastewater release. However, there are no published data for heavy metals present in its sediments and the relationship with anthropogenic disturbance. In the present study, metal concentrations were evaluated in surface sediment samples of the mangrove, showing that B, Cd, Cu, Pb, Se, V, and Zn levels exceeded those declared in international environmental quality standards. Moreover, several metals (Pb, Sn, Cd, Ag, Mo, Zn and Ni) could be linked to the industrial wastewater present in the studied area. In addition, heavy metal levels detected in this mangrove are higher than previous reports on mangrove sediments worldwide, indicating that this mangrove ecosystem is one of the most disrupted on earth.

Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects.

Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss.

The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study: a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control.

INTRODUCTION: The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment. OBJECTIVE: The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach. METHODS: The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice. RESULTS: Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009). CONCLUSIONS: Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications.

The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study; a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control / El estudio RESMENA-S: reducción del síndrome metabólico; una estrategia multidisciplinar basada en la crononutrición y la educación nutricional, junto con control dietético y psicológico

Introduction: The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment. Objective: The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach. Methods: The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice. Results: Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009). Conclusions: Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications (AU)

Introducción: La alta prevalencia del síndrome metabólico (SM) en España requiere de esfuerzos adicionales para su prevención y tratamiento. Objetivo: El estudio RESMENA-S tiene como objetivo mejorar criterios clínicos de SM y biomarcadores asociados a través de un tratamiento integral. Métodos: El estudio consiste en un ensayo aleatorizado de diseño paralelo y prospectivo en el que está previsto participen un total de 100 individuos. El grupo RESMENA-S (n = 50) sigue una dieta personalizada de pérdida de peso (restricción energética 30%), con una distribución en macronutrientes (hidratos de carbono/grasas/ proteínas) de 40/30/30, elevada frecuencia de ingestas (7/día), bajo índice/carga glucémica y elevada capacidad antioxidante y adherencia a la dieta Mediterránea. El grupo control (n = 50) sigue una dieta con la misma restricción energética y basada en la Asociación Americana del Corazón. El estudio tiene una duración de 8 semanas bajo control dietético y psicológico en ambos grupos. Durante un periodo adicional de 16 semanas de auto-control, los voluntarios siguen el mismo patrón dietético pero sin ningún asesoramiento específico. Resultados: Datos antropométricos y de composición corporal, así como muestras sanguíneas y de orina están siendo recogidas al inicio y al final de cada fase. Este proyecto está registrado en www.clinicaltrials.gov con el número NCT01087086 y cuenta con la aprobación del Comité de Ética de Investigación de la Universidad de Navarra (065/2009). Conclusiones: Las intervenciones que favorezcan la adopción de patrones dietéticos y de estilo de vida más saludables, son de elevada importancia para identificar los mecanismos que podrían explicar el nexo de unión entre obesidad, SM y complicaciones asociadas (AU)

Novel polymerase chain reaction primers for the specific detection of bacterial copper P-type ATPases gene sequences in environmental isolates and metagenomic DNA.

AIMS: In the last decades, the worldwide increase in copper wastes release by industrial activities like mining has driven environmental metal contents to toxic levels. For this reason, the study of the biological copper-resistance mechanisms in natural environments is important. Therefore, an appropriate molecular tool for the detection and tracking of copper-resistance genes was developed. METHODS AND RESULTS: In this work, we designed a PCR primer pair to specifically detect copper P-type ATPases gene sequences. These PCR primers were tested in bacterial isolates and metagenomic DNA from intertidal marine environments impacted by copper pollution. As well, T-RFLP fingerprinting of these gene sequences was used to compare the genetic composition of such genes in microbial communities, in normal and copper-polluted coastal environments. New copper P-type ATPases gene sequences were found, and a high degree of change in the genetic composition because of copper exposure was also determined. CONCLUSIONS: This PCR based method is useful to track bacterial copper-resistance gene sequences in the environment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to report the design and use of a PCR primer pair as a molecular marker to track bacterial copper-resistance determinants, providing an excellent tool for long-term analysis of environmental communities exposed to metal pollution.

Soil bacteria are differentially affected by the resin of the medicinal plant Pseudognaphalium vira vira and its main component kaurenoic acid.

The diterpenoid kaurenoic acid is the main component of the resin from the medicinal plant Pseudognaphalium vira vira. As some diterpenoids have antimicrobial properties, the effect of this resin and the kaurenoic acid on soil bacteria was studied. The resin of P. vira vira and purified kaurenoic acid were two to four times more effective as antibacterial agents with Gram-positive than with Gram-negative soil isolates. The chemical stability of kaurenoic acid and the antibacterial activity of both the resin and the diterpenoid were studied in microcosms containing plant-associated soil. After 15 days of incubation, the diterpenoid was stable, as determined by 1H nuclear magnetic resonance and thin-layer chromatography, and soil extracts still exhibited antibacterial activity. However, after 30 days of incubation, loss of antibacterial activity of soil extracts correlated with removal or chemical modification of kaurenoic acid. The effect of the resin or this diterpenoid on the soil bacteria community was analyzed by the terminal restriction fragment length polymorphisms technique. After 15 days of incubation, the resin and the pure compound caused significant changes in the soil bacterial community. The relative abundance of specific bacterial groups was differentially affected by the resin components, being the effects with the resin stronger than with the kaurenoic acid. After 30 days of incubation, these changes mostly reverted. These results indicate that a plant resin containing diterpenoid compounds plays a significant role controlling specific groups of microorganisms in the soil associated with the plant.

Factors influencing the composition of bacterial communities found at abandoned copper-tailings dumps.

AIMS: To study the effect that copper residues exert on bacterial communities and the ability of bacteria to colonize different microhabitats in abandoned tailing dumps. METHODS AND RESULTS: We used the terminal-restriction fragment length polymorphism technique, a culture-independent molecular approach based on PCR amplification of ribosomal genes, to compare the structure of the bacterial communities from samples taken at two nearby located abandoned tailing dumps found in the Mediterranean-climate area of central Chile. Our results show that elevated available copper content in tailings has a strong effect on the bacterial community composition, but that other factors like pH and organic matter content also play an important role in the structure of these communities. We also found that the number of abundant bacteria in these samples was significantly lower than in soils not exposed to metal pollution. CONCLUSIONS: In addition to bioavailable copper, bacterial communities found in copper-tailings dumps are also affected by several other environmental factors. SIGNIFICANCE AND IMPACT OF THE STUDY: This first report on environmental factors influencing microbial communities in copper-tailings dumps will help to devise appropriate restoration procedures in this type of polluted habitat.

Genetic organization of the catabolic plasmid pJP4 from Ralstonia eutropha JMP134 (pJP4) reveals mechanisms of adaptation to chloroaromatic pollutants and evolution of specialized chloroaromatic degradation pathways.

Ralstonia eutropha JMP134 (pJP4) is a useful model for the study of bacterial degradation of substituted aromatic pollutants. Several key degrading capabilities, encoded by tfd genes, are located in the 88 kb, self-transmissible, IncP-1 beta plasmid pJP4. The complete sequence of the 87,688 nucleotides of pJP4, encoding 83 open reading frames (ORFs), is reported. Most of the coding sequence corresponds to a well-conserved IncP-1 beta backbone and the previously reported tfd genes. In addition, we found hypothetical proteins putatively involved in the transport of aromatic compounds and short-chain fatty acid oxidation. ORFs related to mobile elements, including the Tn501-encoded mercury resistance determinants, an IS1071-based composite transposon and a cryptic class II transposon, are also present in pJP4. These mobile elements are inefficient in transposition and are located in two regions of pJP4 that are rich in remnants of lateral gene transfer events. pJP4 plasmid was able to capture chromosomal genes and form hybrid plasmids with the IncP-1 alpha plasmid RP4. These observations are integrated into a model for the evolution of pJP4, which reveals mechanisms of bacterial adaptation to degrade pollutants.

A prospective, randomized study in critically ill patients using the Oligon Vantex catheter.

Microbial colonization and the incidence of catheter-related bloodstream infections (CR-BSI) associated with Oligon Vantex silver central venous catheters (CVC) in critically ill patients were determined. A prospective, randomized, controlled 17-month trial was carried out in an intensive care unit (ICU). All patients requiring a triple-lumen CVC for four days or longer were enrolled. Patients were randomized to receive a standard polyurethane CVC or an Oligon Vantex silver CVC. Before removal of the catheter either due to discharge from the ICU or suspected infection, blood for cultures was taken via the CVC and a peripheral site. Skin and hub swabs and catheter-tips were also cultured. Two hundred and six catheters, 103 in both groups, were evaluated. In the control group (CG) 45/103 (44%) and in the silver group (SG) 30/103 (29%) were colonized or had a CR-BSI (P=0.04). The SG was less likely to be colonized than the CG when the catheter remained in situ for eight days or less (P=0.03) or over 15 days (P=0.01); a second or subsequent catheter was present in the same patient (P=0.002), or if the CVC was placed in the internal jugular vein (P=0.05). Multivariate logistic-regression showed predisposing factors for catheter colonization were jugular and femoral sites, second or subsequent catheter, and being a member of the CG. CR-BSI occurred in five cases (four in CG). Rates of CR-BSI per 1000 catheter-days in the CG were 2.8 and in the SG, 0.8 (P<0.001). The Oligon Vantex silver catheter reduced the incidence of catheter-colonization and may decrease the risk of CR-BSI.

Gas exchange response to a PAF receptor antagonist, SR 27417A, in acute asthma: a pilot study.

The pathogenic role of platelet-activating factor (PAF) in asthma has been questioned due to the limited or negative efficacy of PAF antagonists; however, in acute asthma (AA), where the endogenous release of PAF may be enhanced, the effects of PAF antagonist receptors have not been investigated. It was postulated that inhaled PAF provokes gas exchange defects in mild asthma likely to be related to airway vascular leakage. The response to a potent, selective PAF receptor antagonist, SR 27471A, on pulmonary gas exchange was studied, more specifically ventilation-perfusion (VA'/Q') distributions, in patients with AA within 48 h of hospitalization. A randomized, double-blind, placebo-controlled, parallel group (n=6, each) design was used. After baseline measurements, either placebo or SR 27417A (20 mg, orally) was administered and measurements were repeated 3 h later. Conventional anti-asthma medication was not interrupted. Despite a near-complete inhibition of the in vitro, platelet aggregation tests by 40 nM PAF (mean+/-SEM from 72+/-9 to 6+/-2%) and 80 nM PAF (from 81+/-7 to 6+/-3% both p<0.01) by SR 27471A indicating a good bioactivity of the compound, no significant changes in baseline forced expiratory volume in one second, (40+/-6%), respiratory system resistance (6.2+/-0.7 cmH2O x L(-1) x s), alveolar-arterial pressure difference for oxygen (5.2+/-0.4 kPa), arterial oxygen tension (9.0+/-0.5 kPa) or VA'/Q' distributions, as expressed by the dispersion of pulmonary blood flow (LogSD Q, 1.07+/-0.09; normal values <0.60), were observed. It is concluded that SR 27417A has limited value when added to the conventional treatment of acute asthma. These findings minimize the potential pathogenic role of endogenous platelet-activating factor as a relevant mediator of airway inflammation during acute asthma.

Effect of nitric oxide synthesis inhibition with nebulized L-NAME on ventilation-perfusion distributions in bronchial asthma.

Patients with clinically stable asthma may show ventilation-perfusion (V'A/Q') mismatch. Nitric oxide (NO), a potent endogenous vasodilator, is increased in exhaled air of asthmatics. Such an increased NO production may be detrimental for optimal V'A/Q' balance owing to the potential inhibition of hypoxic pulmonary vasoconstriction. This study was undertaken to investigate the relationship between the concentration of NO in exhaled air and the degree of gas-exchange impairment and to assess the effect of nebulized N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthesis, on gas exchange in patients with asthma. Twelve patients (four females and eight males, aged 31+/-5 yrs) with clinically stable asthma (forced expiratory volume in one second (FEV1) 80+/-5%) not treated with glucocorticoids and increased exhaled NO (58+/-9 parts per billion (ppb)) were studied. Exhaled NO, respiratory system resistance (Rrs), arterial blood gases and V'A/Q' distributions were measured before and 30, 60, 90 and 120 min after placebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured. At baseline no relationships between exhaled NO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p< 0.001), which was maximal at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, arterial oxygen tension, the alveolar-arterial pressure difference in oxygen or V'A/Q' distributions were shown and nebulized L-NAME did not modify pulmonary artery pressure. In conclusion, the degree of gas-exchange impairment in stable asthma is not related to nitric oxide concentration in exhaled air and nitric oxide synthesis inhibition with N(G)-nitro-L-arginine methyl ester does not alter gas exchange or pulmonary haemodynamics, such that ventilation-perfusion disturbances do not appear to be related to an increased synthesis of nitric oxide in the airways.

Gas exchange and pulmonary haemodynamic responses to fat emulsions in acute respiratory distress syndrome.

OBJECTIVE: To investigate the gas exchange and pulmonary haemodynamic responses to two different intravenous fat emulsions in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: 21 patients with ARDS [mean age, 57 +/- 3 (SEM) years; Acute Physiology and Chronic Health Evaluation II, 20 +/- 3; Murray's score, 2.85 +/- 0.12] consecutively admitted. INTERVENTIONS: Patients were assigned to three groups (n = 7 each): group A (LCT) received long-chain triglycerides (20% LCT), group B (MCT/LCT), medium-chain triglycerides/long-chain triglycerides (20% MCT/LCT: 50/50) and group C placebo (0.9% sodium chloride, NaCl). The infusion was always given at the rate of 2 mg/kg min over a total period of 12 h, with a volume infusion of 500 ml in each group. MEASUREMENTS: Data were collected before, immediately after and 12 h after infusion ceased. Pulmonary and systemic haemodynamic and gas exchange variables were measured at each time point. Serum triglyceride cholesterol, and non-esterified fatty acids levels were measured. RESULTS: During LCT infusion, cardiac output, oxygen consumption and oxygen delivery increased (all p < 0.05), whereas pulmonary haemodynamics, arterial oxygen tension, mixed venous partial pressure of oxygen and venous admixture ratio remained essentially unaltered. No changes were observed following MCT/LCT infusion. CONCLUSIONS: The administration of LCT emulsion given at a slow rate did not alter arterial oxygenation because of the beneficial effect of a high cardiac output, hence offsetting the detrimental effect of increased O2 consumption.

The effects of 5-lipoxygenase inhibition by zileuton on platelet-activating-factor-induced pulmonary abnormalities in mild asthma.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of asthma. We investigated whether PAF-induced neutropenia and lung function disturbances are secondary to activation of the 5-lipoxygenase (5-LO) pathway with the consequent liberation of leukotrienes. The effect of a selective 5-LO inhibitor (zileuton) was examined in 10 mildly asthmatic patients (24 +/- 1 [mean +/- SE] yr; FEV1 = 94 +/- 4% predicted) before and after PAF inhalation, in a randomized, double-blind, placebo-controlled, crossover fashion. Patients were studied at baseline, 3 h after an oral single dose of zileuton (600 mg) or placebo, and then at 5 min, 15 min, and 45 min after PAF (18 microg) inhalation. Compared with vehicle, premedication with zileuton reduced both PAF-induced neutropenia at 5 min (by 43%) (p < 0.005) and the subsequent rebound neutrophilia at 15 min and 45 min (by 50% and 47%, respectively) (p < 0.025 each). In addition, at 5 min after PAF inhalation, zileuton attenuated increases in respiratory system resistance (Rrs) (by 39%) (p < 0.01) and in the alveolar-arterial PO2 difference (A-a)PO2 (by 40%) (p < 0.05), and the decrease in PaO2 (by 27%) (p < 0.005). The protective effect of zileuton against PAF-induced ventilation-perfusion (VA/Q) defects was shown by a parallel improvement (decrease) in an overall marker of VA/Q inequality (dispersion of retention minus excretion of inert gases corrected for dead space; DISP R-E.) (by 43%) 5 min after administration of PAF (p < 0.01). These findings indicate that PAF-induced systemic and pulmonary effects in patients with mild asthma are effectively mediated by the ongoing release of leukotrienes.

Severe acute pancreatitis: treatment with somatostatin.

OBJECTIVE: To investigate the efficacy of somatostatin for the treatment of severe acute pancreatitis. DESIGN: Prospective, randomized and unblinded study. SETTING: A general intensive care unit (ICU) in a university hospital. PATIENTS: 50 patients with severe acute pancreatitis. INTERVENTIONS: All patients received the conventional treatment for this clinical condition. The study group received, in addition, somatostatin over a 10-day period. MEASUREMENTS AND RESULTS: We evaluated age, gender, etiology of the pancreatitis, severity of the illness, complications, length of hospitalization, and mortality in the ICU. The patients were classified as severe (Acute Physiology and Chronic Health Evaluation II score, Ranson's criteria, and computed tomography Balthazar classification). Biliary lithiasis was the most common etiologic factor (63.6% in the control group, 37.5% in study group; NS). The study group required fewer overall surgical interventions than the control group (45.8 vs 86.4%; p = 0.005). Late surgical procedures related to the evolution of pancreatic necrosis were more common in the controls (63.6 vs 37.5%; p = 0.07). No differences in length of stay in hospital or mortality in the ICU were observed. CONCLUSION: The only advantage of somatostatin administration in the patients studied was a slight reduction in the need for surgery due to local complications.

Effects of noninvasive ventilation on pulmonary gas exchange and hemodynamics during acute hypercapnic exacerbations of chronic obstructive pulmonary disease.

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 +/- 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (I) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 +/- 2 cm H20, PEEP = 3 +/- 2 cm H20); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping FIO2 constant (0.23 +/- 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in Pa02 (from 50 +/- 6 to 57 +/- 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 +/- 10 to 59 +/- 10 mm Hg; p < 0.0001), but AaPO2 increased (from 39 +/- 13 to 48 +/- 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 +/- 5 to 19 +/- 3 breaths/min; p < 0.0001), tidal volume increased (from 311 +/- 42 to 520 +/- 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 +/- 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 +/- 1.6 to 5.8 +/- 1.3 L/min; p < 0.0025) with no impact on mixed venous PO2. No substantial changes in VA/Q mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 +/- 0.17 to 0.90 +/- 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in VA/Q relationships. The increase in AaPO2 was explained by the rise in R due to an increased clearance of body stores of C02 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NlPPV in this type of patient.