Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery.

PURPOSE: To describe the change in ventilatory practice in a tertiary paediatric intensive care unit (PICU) in the 5-year period after the introduction of high-flow nasal prong (HFNP) therapy in infants <24 months of age. Additionally, to identify the patient subgroups on HFNP requiring escalation of therapy to either other non-invasive or invasive ventilation, and to identify any adverse events associated with HFNP therapy. METHODS: The study was a retrospective chart review of infants <24 months of age admitted to our PICU for HFNP therapy. Data was also extracted from both the local database and the Australian New Zealand paediatric intensive care (ANZPIC) registry for all infants admitted with bronchiolitis. RESULTS: Between January 2005 and December 2009, a total of 298 infants <24 months of age received HFNP therapy. Overall, 36 infants (12%) required escalation to invasive ventilation. In the subgroup with a primary diagnosis of viral bronchiolitis (n = 167, 56%), only 6 (4%) required escalation to invasive ventilation. The rate of intubation in infants with viral bronchiolitis reduced from 37% to 7% over the observation period corresponding with an increase in the use of HFNP therapy. No adverse events were identified with the use of HFNP therapy. CONCLUSION: HFNP therapy has dramatically changed ventilatory practice in infants <24 months of age in our institution, and appears to reduce the need for intubation in infants with viral bronchiolitis.

Benzo(a)pyrene enhances atherosclerosis in White Carneau and Show Racer pigeons.

Benzo(a)pyrene (BaP), a major environmental pollutant and component of cigarette smoke, is both carcinogenic and atherogenic in experimental models. We investigated the effect of long-term administration of BaP on atherogenesis in both atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons. The number and size of arterial lesions in the brachiocephalic arteries in WC and SR females but not males were significantly enhanced after long-term dosing with BaP. Metabolic activation appears to be required for BaP atherogenicity, since benzo(e)pyrene (BeP), a noncarcinogenic analogue of BaP, did not enhance lesion development. Studies with 3H-BaP revealed no significant differences between male and female or between WC and SR pigeons in the arterial distribution of BaP and/or its metabolites. There were no consistent differences in blood pressure or plasma cholesterol levels between breeds or sexes. However, chronic administration of BaP did result in complete infertility in female birds, concomitant with grossly visible changes in ovarian appearance. These results clearly show that long-term dosing with BaP alters ovarian structure and function in treated birds, at the same time aggravating the development of arterial lesions. Thus, BaP-induced atherogenicity in female pigeons may be a consequence of an alteration in estrogen production or of antiestrogenic properties of BaP at the level of the arterial wall and may serve as a highly useful animal model to examine the well-known rapid development of atherosclerosis in postmenopausal women.

Effect of vitamin A on longevity.

Increasing the dietary content of Vitamin A from inadequate to adequate during the developmental stages of Drosophila increased the median life span by as much as 17.5%. The optimum dietary range of concentrations of Vitamin A for increasing the life span of Drosophila was found to be between 4 and 8 IU/g food. The maximum life span was reduced as dietary concentrations of Vitamin A exceeded this value. Vitamin A palmitate and retinal inhibited the peroxidation of linolenic acid induced by the generation of superoxide radicals from acetaldehyde. Other forms of Vitamin A, such as retinol and retinoic acid, moderately inhibited lipid peroxidation at low concentrations but stimulated peroxidation considerably when present at high concentrations. Based upon the ability of these retinoids to inhibit the reduction of cytochrome c by superoxide radicals, we propose that retinoids can inhibit and stimulate lipid peroxidation depending upon their concentration by reacting with superoxide radicals. We suggest that this reaction is the basis for the apparent ability of Vitamin A to prolong and shorten life span depending upon the dietary intake.

Accumulation of malondialdehyde in mouse heart following acute dosing with adriamycin is strain specific and unaffected by cardiac catalase status.

CDF1 and C57BL/6J male mice were acutely dosed with Adriamycin (ADR), and total cardiac malondialdehyde (MDA) quantitated following isolation by modification of previously developed procedures. Cardiac MDA content in CDF1 mice increased significantly 5 days following ADR dosing as reported by others, but was unchanged in C57BL/6J mice. ADR-induced mortality and a significant loss in cardiac weight 2-3 days after treatment was similar in both strains. Cardiac lipid hydroperoxide (LH) content was also unchanged in C57BL/6J mice dosed acutely with ADR. However, hepatic LH content increased rapidly following treatment with ADR, reaching maximal level 1 day following treatment before returning to below untreated levels 24 hours later. Studies with genetically acatalasemic C57BL/6J mice showed that neither cardiac nor hepatic lipid hydroperoxide content in ADR-dosed animals is affected by tissue catalase levels. These results demonstrate that C57BL/6J mouse heart is refractory to ADR-induced lipid peroxidation (LP) although overall mortality from the drug is unaffected, and do not support the hypothesis that ADR-induced mortality in mice is a consequence of cardiac LP.

Effect of 17 beta estradiol on aortic cholesterol content and metabolism in cholesterol-fed rabbits.

Administration of estrogen to cholesterol-fed rabbits dramatically retarded arterial lesion development despite its lack of effect on plasma cholesterol concentration and on lipoprotein patterns. Cholesteryl ester influx into the aortic wall was also much lower in the estrogen-treated animals and paralleled the aortic cholesterol content in treated and untreated animals; the fraction of aortic cholesteryl ester lost by efflux was the same in treated and untreated animals. The fraction of newly entered cholesteryl ester hydrolyzed by aorta was significantly reduced in the estrogen-treated animals. Low cholesteryl ester influx and relatively less hydrolysis of cholesteryl ester by the aorta may be indicative of reduced internalization of plasma cholesteryl ester by aortic cells, which may in turn account for the reduced atherogenesis in the estrogen-treated rabbits.

Influx, efflux, and hydrolysis of cholesteryl ester in atheromatous lesions of cholesterol-fed rabbits.

Total plasma lipoproteins were labeled with radioactive cholesteryl ester or cholesteryl ether by transfer of these lipids from phosphatidylcholine vesicles in the presence of plasma lipid transfer activity. Intravenous injection of these preparations into hypercholesterolemic rabbits showed disappearance curves identical to those of in vivo labeled lipoproteins. Disappearance of cholesteryl ester and ether were similar during the first 24 hours, but they diverged at later time intervals, indicating recirculation of labeled cholesteryl ester. Lipoproteins labeled with cholesteryl ether were injected at 25 days, 7 days and 1 day before sacrifice of the rabbits. The maximal loss of labeled ether from the aortas during a 24-hour period ranged from 1.6% to 8.9% of the labeled ether taken up from plasma. Hydrolysis of cholesteryl ester by the artery during 24 hours averaged 35% of the calculated cholesteryl ester influx. After hydrolysis, cholesteryl ester fatty acid appeared to be esterified more rapidly than the cholesterol moiety of the cholesteryl ester.

Comparison of various methods for in vitro cholesteryl ester labeling of lipoproteins from hypercholesterolemic rabbits.

Little or no information is available on biologically valid labeling of hypercholesterolemic plasma lipoproteins with cholesteryl ester. The esterification of labeled unesterified cholesterol in hypercholesterolemic rabbit plasma by the lecithin: cholesterol acyltransferase reaction is inefficient. The use of the d greater than 1.063 plasma fraction for this reaction greatly improves the efficiency, but some labeled unesterified cholesterol remains in the end products. The latter disadvantage can be avoided by the addition to whole plasma of labeled cholesteryl ester dissolved in DMSO or acetone. However, in hypercholesterolemic rabbit plasma only a small fraction of the added cholesteryl ester was associated with lipoproteins. When phosphatidylcholine/cholesteryl ester liposomes were incubated with hypercholesterolemic rabbit plasma for 18-24 h at 37 degrees C the labeled cholesteryl ester was quantitatively incorporated into lipoproteins. Chylomicron-like, cholesteryl ester-rich particles were removed by centrifugation (10(6) g X min) and the subsequently isolated d less than 1.019 and d = 1.019-1.063 (LDL) fractions were injected intravenously into normal and hypercholesterolemic rabbits. The disappearance of d less than 1.019 and LDL cholesteryl ester and the appearance of cholesteryl ester in other lipoprotein fractions was indistinguishable from that of in vivo-labeled lipoproteins. In vivo and in vitro cholesteryl ester-labeled lipoproteins were also compared by measuring the exchangeability of their cholesteryl ester with HDL cholesteryl ester in vitro. Equal exchangeability of the two labels was observed in the d less than 1.019 fraction from which the chylomicron-like particles had been removed. These findings demonstrate that when cholesteryl ester is incorporated by the liposome procedure, the distribution of labeled cholesteryl ester within the lipoprotein complex corresponds closely to that of the in vivo-incorporated labeled cholesteryl ester.