Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Elevated Plasma Hemoglobin Levels Increase Nitric Oxide Consumption in Experimental and Clinical Acute Pulmonary Thromboembolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pediatric Perioperative Cardiac Arrest and Mortality: A Study From a Tertiary Teaching Hospital

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparison between noninvasive mechanical ventilation and standard oxygen therapy in children up to 3 years old with respiratory failure after extubation: a pilot prospective randomized clinical study

Objectives: The effectiveness of noninvasive positive-pressure ventilation in preventing reintubation due to respiratory failure in children remains uncertain. A pilot study was designed to evaluate the frequency of extubation failure, develop a randomization approach, and analyze the feasibility of a powered randomized trial to compare noninvasive positive-pressure ventilation and standard oxygen therapy post extubation for preventing reintubation within 48 hours in children with respiratory failure.Design: Prospective pilot study.Setting: PICU at a university-affiliated hospital.Patients: Children aged between 28 days and 3 years undergoing invasive mechanical ventilation for greater than or equal to 48 hours with respiratory failure after programmed extubation.Interventions: Patients were prospectively enrolled and randomly assigned into noninvasive positive-pressure ventilation group and inhaled oxygen group after programmed extubation from May 2012 to May 2013.Measurements and Main Results: Length of stay in PICU and hospital, oxygenation index, blood gas before and after tracheal extubation, failure and reason for tracheal extubation, complications, mechanical ventilation variables before tracheal extubation, arterial blood gas, and respiratory and heart rates before and 1 hour after tracheal extubation were analyzed. One hundred eight patients were included (noninvasive positive-pressure ventilation group, n = 55 and inhaled oxygen group, n = 53), with 66 exclusions. Groups did not significantly differ for gender, age, disease severity, Pediatric Risk of Mortality at admission, tracheal intubation, and mechanical ventilation indications. There was no statistically significant difference in reintubation rate (noninvasive positive-pressure ventilation group, 9.1%; inhaled oxygen group, 11.3%; p > 0.05) and length of stay (days) in PICU (noninvasive positive-pressure ventilation group, 3 [116]; inhaled oxygen group, 2 [1-25]; p > 0.05) or hospital (noninvasive positive-pressure ventilation group, 19 [7-141]; inhaled oxygen group, 17 [8-80]).Conclusions: The study indicates that a larger randomized trial comparing noninvasive positive-pressure ventilation and standard oxygen therapy in children with respiratory failure is feasible, providing a basis for a future trial in this setting. No differences were seen between groups. The number of excluded patients was high.

Oral bisphosphonate-related osteonecrosis of the jaws in rheumatoid arthritis patients: a critical discussion and two case reports

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition characterized by the presence of exposed bone in the maxillofacial region. Its pathogenesis is still undetermined, but may be associated with risk factors such as rheumatoid arthritis (RA). The aim of this paper is to report two unpublished cases of BRONJ in patients with RA and to conduct a literature review of similar clinical cases with a view to describe the main issues concerning these patients, including demographic characteristics and therapeutic approaches applied.Methods: Two case reports of BRONJ involving RA patients were discussedResults: Both patients were aging female taking alendronate for more than 3 years. Lesions were detected in stage II in posterior mandible with no clear trigger agent. The treatment applied consisted of antibiotics, oral rinses with chlorhexidine, drug discontinuation and surgical procedures. Complete healing of the lesions was achieved.Conclusions: This paper brings to light the necessity for rheumatologists to be aware of the potential risk to their patients of developing BRONJ and to work together with dentists for the prevention and early detection of the lesions. Although some features seem to link RA with oral BRONJ and act as synergistic effects, more studies should be developed to support the scientific bases for this hypothesis.

Use of Medicines Among a Brazilian Elderly Sample: A Cross-sectional Study

Background: The use of multiple medicines is very frequent among the elderly, allowing them to perceive more often adverse side effects from drugs and present undesirable drug interactions.Methods: This article presents a cross-sectional survey about the use of medicines among 300 elderly Brazilians, equally divided into institutionalized and community-dwelling groups.Results: The average daily intake of medicines is 3.2 among institutionalized elderly, a higher (p < 0.001) number when compared with community-dwelling elderly, who takes an average of 1.8 medicines daily. The most commonly used medications are antihypertensives (58.0%), diuretics (23.0%), nonsteroidal anti-inflammatory drugs (22.7%), supplements (21.7%), antidiabetics (16.3%), and antiulcerants (14.0%). Antiulcerants, diuretics, supplements, and central nervous system drugs are more frequently used by institutionalized than by community-dwelling elderly.Conclusion: In this Brazilian elderly sample, the most widely used medicines were antihypertensives, diuretics, and nonsteroidal anti-inflammatory drugs, and institutionalized used more medications than community-dwelling elderly. Copyright (C) 2011, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.

A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension

The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. In healthy volunteers at FRC, the distribution of the density histograms was monophasic with a peak at -791 ± 12 Hounsfield units (HU). The lowest CT number observed was -912 HU. At TLC, lung volume increased by 79 ± 35% and the peak CT number decreased to -886 ± 26 HU. More than 70% of the increase in lung volume was located below -900 HU, suggesting that this value can be considered as the threshold separating normal aeration from overdistension. In patients with ALI, at ZEEP the distribution of density histograms was either monophasic (n = 3) or biphasic (n = 3). The mean CT number was -319 ± 34 HU. At PEEP 13 ± 3 cm H2O, lung volume increased by 47 ± 19% whereas mean CT number decreased to -538 ± 171 HU. PEEP induced a mean alveolar recruitment of 320 ± 160 ml and a mean lung overdistension of 238 ± 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.

Effects of gender on stroke rates, critical speed and velocity of a 30-min swim in young swimmers

Our objective was to analyze the effect of gender on the relationship between stroke rates corresponding to critical speed (SRCS) and maximal speed of 30 min (SRS30) in young swimmers. Twenty two males (GM1) (Age = 15.4 ± 2.1 yr., Body mass = 63.7 ± 12.9 kg, Stature = 1.73 ± 0.09 m) and fourteen female (GF) swimmers (Age = 15.1 ± 1.6 yr., Body mass = 58.3 ± 8.8 kg, Stature = 1.65 ± 0.06 m) were studied. A subset of males (GM2) was matched to the GF by their velocity for a 30 min swim (S30). The critical speed (CS) was determined through the slope of the linear regression line between the distances (200 and 400 m) and participant's respective times. CS was significantly higher than S30 in males (GM1 - 1.25 and 1.16 and GM2 - 1.21 and 1.12 m·s-1) and females (GF - 1.15 and 1.11 m·s-1). There was no significant difference between SRCS and SRS30 in males (GM1 - 34.16 and 32.32 and GM2 - 34.67 and 32.46 cycle·s-1, respectively) and females (GF - 34.18 and 33.67 cycle·s-1-1, respectively). There was a significant correlation between CS and S30 (GM1 - r = 0.89, GF - r = 0.94 and GM2 - r = 0.90) and between SRCS and SRS30 (GM1 - r = 0.89, GF - r = 0.80 and GM2 - r = 0.88). Thus, the relationship between SRCS and SRS30 is not influenced by gender, in swimmers with similar and different aerobic capacity levels. ©Journal of Sports Science and Medicine (2007).

Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal alpha-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins - eIF5A(K56A) and eIF5A(Q22H,L93F)- and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression.