Randomised trial of compliance with flexible (C-Flex) and standard continuous positive airway pressure for severe obstructive sleep apnea

Introduction  Obstructive sleep apnea (OSA) is often treated with continuous positive airway pressure (CPAP) but the effectiveness of treatment is probably limited by poor compliance. CPAP manufacturers are thus attempting to devise more comfortable PAP devices in an effort to improve compliance. An example of such a novel device is Flexible expiratory-modulated PAP (C-Flex mode Respironics REMstar Pro, Murraysville, PA, USA). Materials and methods  We aimed to compare compliance between C-Flex and standard CPAP in patients with severe OSA in a randomised controlled trial. Nineteen patients with severe OSA (mean ± SD Apnea Hypopnea Index = 78 ± 33/h, Epworth 14 ± 4, PAP 8–17 cm H₂O, BMI = 39 ± 10 kg/m²) and aged 20–63 years were randomly assigned to 4 weeks of either C-Flex (setting II, n = 9) or CPAP (n = 10). Results  Patients treated with C-Flex exhibited a trend toward higher compliance with their PAP devices compared to patients treated with standard CPAP (4.7 ± 2.9 vs. 3.0 ± 2.1 h/night, p = 0.15, effect size = 0.68). Paradoxically, improvements in subjective sleepiness (Epworth Sleepiness Scale) were greater in those who received CPAP than C-Flex (8.1 + 4.9 vs. 2.1 + 4.0 points, p = 0.014, effect size = 1.46). Improvements in objective wakefulness (Modified Maintenance of Wakefulness Test) and simple reaction times (Psychomotor Vigilance Task) were not significantly different between treatments. This randomised trial provides some evidence that C-Flex might increase initial treatment compliance, compared to CPAP, in patients with severe OSA. However, this trend toward greater compliance was not associated with better short-term treatment outcomes for patients. These findings need to be confirmed in a larger, longer-term trial. Stipend from Massey University (to NSM). None of the authors have had any financial relationships with Respironics Inc., who are the manufacturers of the device tested. Respironics International Inc., through their New Zealand suppliers Care Medical, provided six C-Flex machines for the purposes of this trial.     

Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

Summary Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called ‘Z’ mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. Competing interests: None declared References to electronic databases: Alpha 1-antitrypsin deficiency: +107400. C.M. Greene and S.D.W. Miller contributed equally to the work.     

Novel Atlantic bottlenose dolphin parainfluenza virus TtPIV-1 clusters with bovine PIV-3 genotype B strains

Parainfluenza virus 3 (PIV-3) is a common viral infection not only in humans, but also in many other species. Serological evidence suggests that nearly 100 % of children in the United States have been infected with PIV-3 by 5 years of age. Similarly, in cattle, PIV-3 is commonly associated with bovine respiratory disease complex. A novel dolphin PIV-3 (TtPIV-1) was described by Nollens et al. in 2008 from a dolphin that was diagnosed with an unknown respiratory illness. At that time, TtPIV-1 was found to be most similar to, but distinct from, bovine PIV-3 (BPIV-3). In the present study, similar viral growth kinetics and pro-inflammatory cytokine (IL-1β, IL-6, and CXCL8) production were seen between BPIV-3 and TtPIV-1 in BEAS-2B, MDBK, and Vero cell lines. Initial nomenclature of TtPIV-1 was based on partial sequence of the fusion and RNA polymerase genes. Based on the similarities we saw with the in vitro work, it was important to examine the TtPIV-1 genome in more detail. Full genome sequencing and subsequent phylogenetic analysis revealed that all six viral genes of TtPIV-1 clustered within the recently described BPIV-3 genotype B strains, and it is proposed that TtPIV-1 be re-classified with BPIV-3 genotype B strains.     

The restriction–modification genes of Escherichia coli K-12 may not be selfish: They do not resist loss and are readily replaced by alleles conferring different specificities

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491–496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as “selfish” units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.     

Impact of catheter ablation versus medical therapy on cognitive function in atrial fibrillation: a systematic review

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation is associated with an increased risk of cognitive impairment. It is unclear whether the restoration of sinus rhythm with...     

Subendocardial ischemia provoked by tachycardia in conscious dogs with coronary stenosis

We investigated the effect that mild coronary stenosis exerts on the ability of the coronary circulation to compensate for the increased extravascular compression that occurs in the subendocardium during tachycardia. An electromagnetic flowmeter transducer and balloon cuff occluder were implanted on the left circumflex coronary artery in seven dogs, and experiments were performed 1 week later with the dogs under sedation but conscious. Stenosis of the left circumflex artery was produced by partial inflation of the cuff occluder. We determined coronary blood flow distribution by the radioactive microsphere technique, injecting 200,000 15μ spheres into the left ventricular cavity during (1) a control period, (2) stenosis of the left circumflex artery and a normal heart rate, and (3) stenosis of the left circumflex artery and tachycardia. When the heart rate was normal, the degree of stenosis used caused no change in myocardial microsphere distribution but eliminated postocclusion reactive hyperemia. Thus, reserve coronary vasodilation compensated for the stenosis. With the degree of stenosis kept constant, an increase in heart rate to 196 beats/min caused a marked transmural shift in distribution of microspheres from subendocardium into subepicardium within the region of the left ventricle supplied by the left circumflex artery. There was no significant transmural shift in the region supplied by the uninvolved left anterior descending coronary artery. Myocardial lactate extraction decreased. These results suggest that when reserve coronary vasodilation has already been utilized to compensate for coronary stenosis, the increased extravascular coronary compression from tachycardia causes subendocardial ischemia and hypoxia.