High-flow oxygen therapy v. standard care in infants with viral bronchiolitis.

Background: High-flow humidified oxygen (HFHO) therapy has demonstrated benefit in infants with bronchiolitis. Objectives: To investigate the efficacy of HFHO in infants with moderate to severe viral bronchiolitis, when used outside the paediatric intensive care unit (PICU), in a hospital with limited PICU resources. Methods: A randomised controlled trial, which enrolled 28 infants between 1 month and 2 years of age, with a clinical diagnosis of acute viral bronchiolitis and moderate to severe respiratory distress. Participants were randomised to receive HFHO 2L/kg/min or oxygen by nasal cannula/ face mask. Respiratory rate, heart rate, oxygen saturations, and modified TAL (M-TAL) score were measured at baseline, 60 - 90 minutes after starting therapy and at 6- and 12-hourly intervals. The primary outcome evaluated was the improvement in respiratory distress (M-TAL score). The secondary outcome assessed was the need for intubation and ventilation. Results: There was a significant improvement in respiratory distress (M-TAL score), in infants who received HFHO therapy. Additionally, there was also a reduction in heart rate in the HFHO group as well as a trend to lower intubation rates. Conclusion: HFHO is a beneficial therapy for infants with moderate-severe viral bronchiolitis. It can be safely used outside the PICU and could potentially reduce the need for intubation and admission to PICU in resource-limited settings. Contributions of the study: High-flow humidified oxygen (HFHO) is effective in infants with moderate to severe bronchiolitis, and not only in those with milder forms of the disease. It can be safely used outside the paediatric intensive care unit, where adequate respiratory monitoring is available. This is important in low-resource areas where there may be insufficient critical care resources to manage these patients.

Intrapartum asphyxia and hypoxic ischaemic encephalopathy in a public hospital: Incidence and predictors of poor outcome.

OBJECTIVE: To determine the incidence of asphyxia and hypoxic ischaemic encephalopathy (HIE) and predictors of poor outcome in a hospital in a developing country. METHODS: Neonates of birth weight ≥ 2,000 g who required bag-and-mask ventilation and were admitted with a primary diagnosis of asphyxia from January to December 2011 were included. Medical records were retrieved and maternal and infant data collected and analysed. Infants who had severe HIE and/or died were compared with those who survived to hospital discharge with no or mild to moderate HIE. RESULTS: There were 21 086 liveborn infants with a birth weight of 2 000 g over the study period. The incidence of asphyxia ranged from 8.7 to 15.2/1 000 live births and that of HIE from 8.5 to 13.3/1 000, based on the definition of asphyxia used. In 60% of patients with HIE it was moderate to severe. The overall mortality rate was 7.8%. The mortality rate in infants with moderate and severe HIE was 7.1% and 62.5%, respectively. The odds of severe HIE and/or death were high if the Apgar score was <5 at 10 minutes (odds ratio (OR) 19.1; 95% confidence interval (CI) 5.7-66.9) and if there was no spontaneous respiration at 20 minutes (OR 27.2; 95% CI 6.9-117.4), a need for adrenaline (OR 81.2; 95% CI 13.2-647.7) and a pH of < 7 (OR 5.33; 95% CI 1.31-25.16). Predictors of poor outcome were Apgar score at 10 minutes (p = 0.004), need for adrenaline (p = 0.034) and low serum bicarbonate (p = 0.028). CONCLUSION: The incidence of asphyxia in term and near-term infants is higher than that reported in developed countries. Apgar score at 10 minutes and need for adrenaline remain important factors in predicting poor outcome in infants with asphyxia.

Insights into the mechanisms of sister chromatid exchange formation.

The DNA lesions responsible for the formation of sister chromatid exchanges (SCEs) have been the object of research for a long time. SCEs can be visualized by growing cells for either two rounds of replication in the presence of 5-bromo-2'-deoxyuridine (BrdU) or for one round with BrdU and the next without. If BrdU is added after cells were treated with a DNA-damaging agent, the effect on SCEs can only be analyzed in the second post-treatment mitosis. If one wishes to analyze the first post-treatment mitosis, cells unifilarily labeled with BrdU must be treated. Due to the highly reactive bromine atom, BrdU interacts with such agents like ionizing and UV radiation enhancing the frequency of SCEs. However, its precise role in this process was difficult to assess for a long time, because no alternative technique existed that allowed differential staining of chromatids. We have recently developed a method to differentially label sister chromatids with biotin-16-2'-deoxyuridine-5'-triphosphate (biotin-dUTP) circumventing the disadvantage of BrdU. This technique was applied to study the SCEs induced by ionizing and UV radiation as well as by mitomycin C, DNaseI and AluI. This article is a review of the results and conclusions of our previous studies.

X-irradiation of G1 CHO cells induces SCE which are both true and false in BrdU-substituted cells but only false in biotin-dUTP-substituted cells.

The SCE-test is widely used in genetic toxicology and therefore knowledge of the contribution of BrdU to the formation of spontaneous and induced SCE is of great importance. The present study was undertaken to analyse the role of BrdU in X-ray-induced SCE. If SCE resulted from inversions, rings and double minutes (RDM) would be the asymmetrical counterparts of SCE and should therefore have the same frequencies. Dose-effect relationships of SCE and RDM show that the frequencies of SCE are much higher than those of RDM. We conclude that only a few SCE may represent inversions. In a second set of experiments, endoreduplications were induced in cells irradiated either before or after labelling with BrdU. Analysis of SCE in endoreduplicated chromosomes allows the discrimination of the cell cycle in which they originated. The results show that SCE are only induced in the first cell cycle following irradiation of BrdU-substituted cells, indicating that labelling with BrdU is a necessary prerequisite for the formation of SCE. In order to test this directly, radiation-induced SCE frequencies were studied in cells prelabelled with BrdU or biotin-dUTP in a third set of experiments. The structure of biotin-dUTP suggests that, in contrast to BrdU, it does not give rise to radicals during irradiation. Significantly lower frequencies of SCE were observed in biotin-dUTP-substituted cells than in BrdU-labelled cells. Calculations show that nearly all SCE induced in biotin-dUTP-labelled chromosomes can be explained by chromosomal aberrations (false SCE). In contrast to this, most SCE induced by X-rays in BrdU-labelled cells are not due to chromosomal aberrations, but result from S-dependent lesions (true SCE). This clearly points towards radiation damage in BrdU-moieties as the source of DNA lesions leading to SCE.

Sister chromatid differentiation with biotin-dUTP.

The method of choice to differentiate sister chromatids is to incorporate BrdU in replicating DNA. The disadvantage of BrdU is that its spontaneous or induced radicalization may itself lead to sister chromatid exchanges. Biotin-labelled dUTP is a widely used thymidine analogon for labelling isolated DNA. Its chemical structure suggests that, in contrast to BrdU, it does not give rise to radical formation. We electroporated proliferating Chinese hamster ovary (CHO) cells in the presence of biotin-dUTP which was subsequently detected in metaphase cells with TRITC-conjugated avidin. Microscopic analysis of second mitoses after labelling revealed a clear differential staining of sister chromatids. Thus substitution of thymidine with biotin-dUTP is another method to analyse SCE.

The action of quartz in the presence of iron hydroxides in the human lung.

In 1932 Kettle reported that the fibrogenic action of quartz particles is inhibited when they are coated with iron. Many authors subsequently confirmed this finding. Reif et al., who studied the effect of different iron-ore mine dusts, showed that, like aluminium hydroxide, iron hydroxide has a strong effect in inhibiting the fibrogenic action due to quartz. The findings of this paper, based on an X-ray survey of a group of 7735 iron ore miners, on autopsy examinations, tissue dust analysis and physiological examinations, confirm the view that FeO(OH) is a most powerful inhibiting substance.