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Fleming, I., J. Bauersachs, et al. (1998). "Ca2+-independent activation of the endothelial nitric oxide synthase in response to tyrosine phosphatase inhibitors and fluid shear stress." Circulation Research 82(6): 686-95' Fontijn, A., A. J. Subud"ll, uL (fgZO). "Homogenous chemiluminescent measurement of nitric "t oxide with ozone. Implicati,ons for continous selective monitrong of gaseous air pollutants. " Analytical Chemistry 42: 57 5 -57 9' Foresi, A., G. Bertorelli, et al. (1990;. ;Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission." Chest 98(3): 528-35' Foresi, A., C. Leone, it. (tggl). "EosinJphils, mast cells, and basophils in induced sputum from patients "i with seasonal allergic rhinitis and perennial_asthma: relationship to methacholine responsiveness." Jouiral of Allergy & Clinical Immunology 100(l): 58- 64. Foresti, R., J. E. Clark, et al. (1997). "Thiol compounds interact with nitric oxide in regulating heme oxygenase-l induction in endothelial cells. Involvement of superoxide and peroxynitrile anions." Journal of Biological chqmistr.v 272(29): l84ll:7.' Forstermanil, U., E. I. Closs, ut. (fgga)t T.littic oxide synthase isozymes' Characterization' "t purification, molecular cloning, and functions." Hy!@ 23(6 Pt 2): Il2I-31' Forte, P., M. R. Ogborn, et al. (2006). "A noninvasive, sensitive, specific, and reliable approach to issess whole-body nitric oxide synthesis in children." Pediatric Research 59(5):736-41. Francoeur, C. and M. Denis (1995). "Nitric oxide and interleukin-8 as inflammatory componenrs of cystic fibrosis." Inflammation 19(5): 587-98. Frank, T. L., A. Adisesh, et al. (1998). "Rtlutionship between exhaled nitric oxide and childhood asthma." ocr:O: 158(a): 1032-6. Franklin, P. J., G. L. Hall, et al. (2006). "Exhaled nitric oxide is not reduced in infants with c ystic fibrosi s. " European Respiratory Jour.nal 27 (2) : 3 50-3 . Franklin, p. J., S. M. Stick, et al. (2004;fr--"ururing exhaled nitric oxide levels in adults: the importance of atopy and airway responsiveness." @! 126(5):1540-5. n.unr.rinlt. ;., il. T;prin, et al. (1999). "A community study of exhaled nitric oxide in healthy 1 Fi/1\^ zi 159(l): 69children." 73. Franklin, P. J., S. W. Turner, et al. (2005). "Exhaled nitric oxide is reduced in infants with rhinorrhea. " Pediatric Pulmonolo gy 39(2): I 17 -9' Franklin, P. J., S. W. n -o, u1. "t 6Of;. ;'Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of children." lhorax 58(12): IO48-52' Franklin, p. J., S. W. Turner, et al. (2004i. "Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infanis." European Respiratory Journal 23(3):369-72' Franklin, p. J., S. W. Turner, et al. (2004). "Nl.asuring exhaled nitric oxide in infants during tidal breathing: methodological issues." Pediatric Pulmonology 37(1): 24-30' Freeman, C., S. C. Ciane, et al. 1l9lZ). "Covert reduction in ventilatory surface in rats during prolonged exposure to subacute nitrogen dioxide." American Review of Respiratory Disease 106(a): 563-579. Frey, U., C. Kuehni, et al. (2004). "Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants." American Journal of Respiratory & Critical Care Medicine 170(3): 260-5. Frey, U., J. Stocks, et al. (2000). "Specifications function testing. ERS/ATS Task Force on Testing. European Respiratory Society/ Respiratory Journal M@): 7 3l-40. 295 for equipment used for infant pulmonary Standards for Infant Respiratory Function American Thoracic Society." European
Frey, U., J. Stocks, et al. (2000). "Specification for signal processing and data handling used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society." European Respiratory Journal 16(5): 1016-22. Frostell, C., M. D. Fratacci, et al. (1991). "Inhaled nitric oxide: A selective pumonary vasodilator reversing hypoxic pulmonary vasoconstriction." Circulation. 83: 2038- 2M7. Fujimoto, K., K. Kubo, et al. (1997). "Eosinophil cationic protein levels in induced sputum correlate with the severity of bronchial asthma." Chest ll2(5): l24l-7 . Fujimoto, K., S. Yamaguchi, et al. (2006). "Characteristics of asthma resistant to moderate dose inhaled corticosteroid treatment on bronchial hyperresponsiveness." blgrna! Medicine 45(la): 843-9. Fujimura, M., Y. Nishizawa, et al. (2005). "Predictors for typical asthma onset from cough variant asthma." Journal of Asthma 42(2): 107-11. Funai, E. F., A. Davidson, et al. (1997). "S-nitrosohemoglobin in the fetal circulation may represent a cycle for blood pressure regulation." Biochemical & Biophysical Research Communications 239(3): 87 5-7 . Funakoshi, T., H. Yamabe, et al. (1999). "Increased exhaled nitric oxide and impaired oxygen uptake (VO2) kinetics during exercise in patients with chronic heart failure." Japanese Circulation Journal 63(4): 255-60. Fung, H. L., S. Chong, et al. (1988). "Mechanisms for the pharmacologic interaction of organic nitrates with thiols. Existence of an extracellular pathway for the reversal of nitrate vascular tolerance by N-acetylcysteine." Journal of Pharmacology & Experimental Therapeutics 245(2): 524'30. Furchgott, R. F. (1993). "Nitric oxide: from basic research on isolated blood vessels to clinical relevance in diabetes." Anales de la Real Academia Nacional de Medicina 115(2): 317-3t. Furchgott, R. F. and S. Bhadrakom (1953). "Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs." Journal of Pharmacology & Experimental Therapeutics 108(2): 12943. Furchgott, R. F., D. Jothianandan, et al. (1984). "Endothelium-dependent responses: the last three years." @(38): 1-15. Furchgott, R. F. and J. Y. Zawadzki (1980). "The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine." Nature. 1980 Nov 271288(5789\:373-6. Gabriele, C., E. M. Nieuwhof, et al. (2006). "Exhaled nitric oxide differentiates airway diseases in the first two years of life." Pediatric Research 60(a): 46L-5. Gabriele, C., M. W. Pijnenburg, et al. (2005). "The effect of spirometry and exercise on exhaled nitric oxide in asthmatic children." 16(3): 243-7. Gamble, J. F. (1998). "PM2.5 and mortality in long-term prospective cohort studies: causeeffect or statistical associations?[see comment]." 106(9): 53549. Gannon, P. F., J. Belcher, et al. (1999). "The effect of patient technique and training on the accuracy of self-recorded peak expiratory flow." European Respiratory Journal 14(1): 28-31. Gannon, P. F., D. T. Newton, et al. (1998). "Effect of the number of peak expiratory flow readings per day on the estimation of diurnal variation." Thorax 53(9): 790-2. Garcia-Cardena, G., R. Fan, et al. (1998). "Dynamic activation of endothelial nitric oxide synthase by Hsp90." Nature 392(6678):821-4. 296
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UNIVERSITV OF AUCKI'AND Abstract -
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There was no significant difference
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This is Dedicated: Dedication To th
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New Zealand The Paediatric Departme
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Contents Abstract ........tr Dedica
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6.5.4 The subjects............... .
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XIV
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List of Figures Figure l.l: Top l0
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List of Abbreviations ABPA allergic
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LADA N*N* dimethyl L-arginine LFA1
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t}ryem(eNoS)Typeltrendothelialnifti
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area, some of it has been expanded
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In addition, both of these groups a
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studies conducted throughout the Un
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Video clips of infants with a varie
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the Paediatric Society of New 7*ala
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inhaled anti-cholinergic agents and
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ecommended to monitor asthma at hom
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improvement to 70Vo PEF would have
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Furthermore, investigators have als
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poorer predictor of a diagnosis of
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Bronsky et al. 1998), and a long-te
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SIGN guideline (SIGN 2005) stated "
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In brief, the human airway can be d
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The ability to biopsy has led to st
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small proportion of cells recovered
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methodology of sputum induction and
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et al. 1999; Giannini, Di Franco et
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over a six month treatment prograrn
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There are other studies suggesting
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So is induced sputum in adults and
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asymptomatic patients independent o
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onchial hyper-responsiveness (Reich
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led to research which looked for le
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analyser machines. This thesis pres
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The pollution of the 'great smog of
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adults greater than 65 years (Ostro
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levels compared to those children l
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More recently 'Air Quality Indexes'
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acetylcholine. These were known to
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cyclase does not produce significan
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Garthwaite l99l), and the non adren
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significant complication, this trea
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locus for the enzyme is a susceptib
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NO synthesis and in so doing blocke
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3.1 Chapter 3: The synthesis, react
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BHa = tetrahyrobiopterin, FAD = fla
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(Knowles, McWeeny et al. 1974) and
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more potent at low oxygen tensions
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toxic products such as isoprostanes
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Figure 3.3: The nitric oxide syntha
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providing NO as a neurotransmitter
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The enzyme of this second pathway -
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inappropriate production from comme
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Nicotinamide adenosine dinucleotide
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enzyme and are competitively revers
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4.1 Introduction Chapter 4: Methods
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4.4 Nitrite and nitrate The measure
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insensitive (Braker and Mossman 197
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A group of instruments have been de
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The original group demonstrated tha
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equired it. For example, there was
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helium for 30 minutes to remove Oz.
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(Postlethwait and Bidani 1990; Post
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is set at 5ppm (AIHA 1966) based on
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5.1 Chapter 5: Methodological asses
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wanted to compare the patterns of e
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in different colours that became th
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an advisor for this work and main s
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Delay time: the time between turnin
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led to an increased water content t
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Chapter 6: Methodological studies o
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pulmonary circulation appeared to c
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al found levels of 10.3ppb compared
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Authors and Pap€r Sublect numbers
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only those measured by mouth or low
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6. Check that the pens work. Fill w
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keys but it is currently in the mid
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Calibration pressures: the test por
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T-piece: tO The first figure shows
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the rotameter. Tracings of each par
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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subjects with respiratory disease,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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had last used her p2 agonist inhale
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higher level of exhaled NO at 4.9pp
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9.1 Introduction Chapter 9: Exhaled
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For the oral measurements options i
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Table 9.1: The recommended standard
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taken from the available literature
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compartment correlated with the ser
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measurement with variable expirator
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to settle. We may have been measuri
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9.5 Off-line measurement NO determi
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(Hyde, Geigel et al. 1997; Tsoukias
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9.6 Nasal nitric oxide measurement
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measured over two 24 hour periods,
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women who coincidently experienced
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While these cross-sectional and the
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symptoms. Steroid response was sign
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'difficult asthma' also had higher
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season and then reduced down to bas
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of cross sectional studies with a t
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Ciabattoni et al. 2004; Petersen, A
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FEV9.5, symptom score and airways r
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Indomethacin - This medication alte
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89Vo for PCD, and above that exclud
Page 267 and 268: This low NO occurs despite higher t
Page 269 and 270: patients were followed through one
Page 271 and 272: differences noted based on filter,
Page 273 and 274: 9.L6 Nitric oxide levels in exercis
Page 275 and 276: another study of 111 school childre
Page 277 and 278: Almost all studies used sedation, w
Page 279 and 280: peak exhaled NO production in the f
Page 281 and 282: flow and to minimize nasal contamin
Page 283 and 284: ecruit blood vessels in the lung. S
Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291 and 292: o Cass Byrnes & Nicky Holt. "Drugs
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: Appendix 2: Questionnaire for enrol
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: Archer, S. L., P. J. Shultz, et al.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317: Emi-Miwa, M., A. Okitani, et al. (1
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333 and 334: Kercsmar, C. M. (2006). Wheezing in
Page 335 and 336: Kleinert, H., T. Wallerath, et al.
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
Page 341 and 342: Lymar, S. V. and J. K. Hurst (1996)
Page 343 and 344: Massaro, A. F., S. Mehta, et al. (1
Page 345 and 346: Miyabara, Y., R. Yanagisawa, et al.
Page 347 and 348: contribute to impaired endothelium-
Page 349 and 350: ODell, T. J., R. D. Hawkins, et al.
Page 351 and 352: Panza, J. A., C. E. Garcia, et al.
Page 353 and 354: Peters, S. P. (2006). "Safety of in
Page 355 and 356: Prieto, L., L. Bruno, et al. (2003)
Page 357 and 358: Ribbons, K. A., X. J. Zhang, et al.
Page 359 and 360: Sacco, O., R. Sale, et al. (2003).
Page 361 and 362: Sessa, W. C., K. Pritchard, et al.
Page 363 and 364: Silvestri, M., F. Sabatini, et al.
Page 365 and 366: Stamler, J. S. (1994). "Redox signa
Page 367 and 368: Stuehr, D. J., N. S. Kwon, et al. (
Page 369 and 370:
Tierney, W. M., J. F. Roesner, et a
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Upchurch, G. R., G. N. Welch, et al
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Wadsworth, R., E. Stankevicius, et
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Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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