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Hibbs, J. B., Jr., R. R. Taintor, et al. (1988). "Nitric oxide: a cytotoxic activated macrophage effector molecule." Biochemical & Biophysical Research Communications 157(1): 87-94. Hibbs, J. B., Jr., Z. Vavrin, et al. (1987). "L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells." Journal of Immunology 138(2): l-5-0-6:' Hickey,M.J.,K.A@.''Induciblenitricoxidesynthase-deficientmice have enhanced leukocyte-endothelium interactions in endotoxemia." FASEB Journal ll(r2):955-64. Hierholzer, C., B. Harbrecht, et al. (1998). "Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock." Journal of Experimental Medicine 187(6): 917 -28' Higgins, B. G., J. R. B"'tton, et al. (1992). "Comparison of bronchial reactivity and peak expiratory flow variability measurements for epidemiologic studies." American Review of Respiratory Disease 145(3): 588-93' uiggin,ffital.(1989).''Thedistributionofpeakexpiratory!l-y variability in a population sample." American Review of Respiratory Disease 140(5): 1368-72. Higgins, B. G., J. R. Britton, et al. (1993). "Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample"'Thorax 48(9): 899-905' Hiltermann, T. J., J. Stolk, et at. (tggg). "Asihma severity and susceptibility to air pollution"' European Respiratory Journal f 1(3): 686-93' Hirata,K.,R'ru,offi995}-Intriuitionofendothelialnitricoxidesynthaseactivityby protein kinase C." Hypertension 25(2):180-5' "Exhaled nitric oxide is not elevated in the inflammatory Ho, L. p., J. A. Innes, "t iltg98)t airways diseases of cystic fibrosis and bronchiectasis." European Respiratory Journal 12(6): 1290-4. Ho, L. P., F. T. Wood, et al. (2000). "Atopy influences exhaled nitric oxide levels in adult asthmatics." b! 118(5): L327-31. Ho, L. P., F. T. Wood, et al. (2000). "The culrent exhales nitric oxide is affected by airway single exhalation method of measuring calibre." European Respiratory Journal 15(6): 1009-13. Hobbs, M. R., V. Udhayakumar, et al. (2002). "A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children." Lancet 3ffi(9344):1468-75. Hoekstra, M. O., M. H. Grol, et al. (1998). Tosinophil and mast cell parameters in children with stable moderate asthma." Pediatric Allergy & tmmunology 9(3):143-9' Hogg, J. C. (Lggl). "The pathology of asthma." APMIS 105(10): 735-45. uoliian, vt., t. Holmkvist, et at. (zoo2). "Increased nitric oxide elimination from the ainvays after smoking cessation." Clinical Science 103(l): 15-9' Hogman, M., T. UJlmtvist, "t ul. tZOOa. g*t"nded NO analysis appligd- to patients with COpD, allergic asthma and allergic rhinitis." Respiratory Medipine 96(1): 24-30' Hogman, M., S. Stiomberg, et al. (19-97). "Nitric oxide from the human respiratory tract efficiently quantifiei by standardized single breath measurements." Acta Physiologica Scandinavica. APr: 159(a): 345-6. HotU"rg, C. f.3. l;Wti-gnt, et ai. (1993). "Child day care, smoking by caregivers' and lower respiratory tract il'iness in the rirsi 3 years of life. Group Health Medical Associates." Pediatrics 91(5): 885-92. Holcroft, C. A., E. A.'Eisen, et al. (2003). "Measurement characteristics of peak expiratory flow." Chest 124(2): 50 1- 10. 303
Holgate, S. T., D. E. Davies, et al. (2000). "Epithelial-mesenchymal interactions in the pathogenesis of asthma." Journal of Allergy & Clinical Immunology 105(2 Pt 1): 193- 204. Holz, O., R. A. Jorres, et al. (1998). "Changes in sputum composition during sputum induction in healthy and asthmatic subjects." Clinical & Experimental Allergy 28(3): 284-92. Holz, O., J. Kips, et al. (2000). "Update on sputum methodology." European Respiratory Joumal 16(2):355-9. Holz, O., K. Richter, et d. (1998). "Changes in sputum composition between two inductions performed on consecutive days." Thorax 53(2): 83-6. Holzmann, S. (1982). "Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips." Journal of Cyclic Nucleotide Research 8(6): 409-19. Homer, R. J. and J. A. Elias (2000). "Consequences of long-term inflammation. Airway remodeling. " @ 2l(2): 33 I43. Hopp, R. J., A. K. Bewtra, et al. (1984). "Specificity and sensitivity of methacholine inhalation challenge in normal and asthmatic children." Journal of Allergy & Clinical Immunology 7 4(2): 1 54-8. Hopp, R. J., J. A. Degan, et al. (1995). "Cross-sectional study of bone density in asthmatic children. " Pedi atric Pulmonology 20(3): 189 -92. Horak, F., Jr., M. Studnicka, et al. (2002). "Particulate matter and lung function growth in children:a3-yrfollow-upstudyinAustrianschoolchildren.''@ Journal 19(5): 838-45. Horvath, E. P., G. A. doPico, et al. (1978). "Nitrogen dioxide-induced pulmonary disease: five new cases and a review of the leterature." Journal of Occupational Medicine 20(2): 103-10. Horvath, I., L. E. Donnelly, et al. (2004). "Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers." Respiration 71(5): 463-8. Horvath, I., S. Loukides, et al. (2003). "Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia." !.horax, 58(l): 68-72. Hoshino, M., Y. Nakamura, et al. (1998). "Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammation." Journal of Allergy & Clinical Immunolog!, 102(5): 783-8. Hossain, S. (1973). "Quantitative measurement of bronchial muscle in men with asthma." American Review of Respiratory Disease 107(1): 99-109. Howie, S., L. Voss, et al. (2005). "Tuberculosis in New Zealand,1992-2001: a resurgence." Archives of Disease in Childhood 90(11): lI57-6L. Hoyt, J. C., R. A. Robbins, et al. (2003). "Cigarette smoke decreases inducible nitric oxide synthase in lung epithelial cells." Experimental Lung Research 29(I): l7-28. Huang, J., R. Olivenstein, et al. (1999). "Enhanced proteoglycan deposition in the airway wall of atopic asthmatics." American Journal of Respiratory & Critical Care Medicine 160(2):725-9. Huang, P. L., T. M. Dawson, et al. (1993). "Targeted disruption of the neuronal nitric oxide synthase gene." Cell 75(7): 1273-86. Huber, H. L. and K. K. Koessler (L922). "The pathology of bronchial asthma." Archives of Internal Medicine. 30: 689-. Hugod, C. (1979). "Effect of exposure to 43 ppm nitric oxide and 3.6 ppm nitrogen dioxide on rabbit lung. A light and electron microscopic study." International Archives of Occupational & Environmental Health 42Q-0: 159-67. Hugod, C. (1979). "Ultrastructural changes of the rabbit lung after a 5 ppm nitric oxide exposure." Archives of Environmental Health 34(l): l2-7. 304
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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
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This low NO occurs despite higher t
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patients were followed through one
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differences noted based on filter,
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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 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319 and 320: Frey, U., J. Stocks, et al. (2000).
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325: Hashimoto, T., K. Minoguchi, 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
Page 371 and 372: Upchurch, G. R., G. N. Welch, et al
Page 373 and 374: Wadsworth, R., E. Stankevicius, et
Page 375 and 376: Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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