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Appendix I : Publications Published manuscripts related to this thesis: Appendices o ,.Trying to catch our breath" The burden of preventable breathing diseases in children and young people. Editors Innes Asher and Cass Byrnes. Asthma and Respiratory Foundation of New 7-ealand. Te Taumatua Huango, Mate Ha o Aoteroa' www'asthmanz'co'nz and www.paedi atrics.org.nz. C A Byrnes: Chapter 9: The Burden of Bronchiolitis in New Zealand (40-45)' c A Byrnes: Chapter I 1: The Burden of Bronchiectasis in New T.r,aland (51-55)' o Byrnes cA, Dinarevic s, shinebourne EA, Barnes PJ, Bush A. I-evels Of nitric oxide in exhaled air in normal and asthmatic children. Pediatric Pulmonolo gy 1997 24 (5) 312-318' o Byrnes CA, Dinarevic S, Busst CA, Shinebourne EA, Bush A' Effect of measurement conditions on measured levels of peak exhaled nitric oxide. Thorax 1997 52 (8) 697-701' o Byrnes cA, Dinarevic S, Busst cA, Bush A, Shinebournes EA. Is nitric oxide produced at airway or alveolar level? European Respiratory Journal 1997 l0 (5) 1021-1025' o Dinarevic s, Byrnes cA, Shinebourne EA, Bush A. Measurement of exhaled nitric oxide in children. Pediatric Pulmonolo gy 1996; 22: 396-40L' o Byrnes CA, Bush A and shinebourne EA "Methods to Measure Expiratory Nitric oxide in People" in "A Volume of Methods in Enzymology" edited by I-ester packeter Academic Press Inc. 1996. Publications based on research that has progressed from this thesis: o phD thesis: .Nitric oxide and ciliary beat in normal and bronchiectatic children'' Dr Elizabeth Edwards awarded 2004 (2001-2004)' Prinicipal supervisor: Dr Cass Byrnes' o Edwards EA, Douglas C, Broome S, Kolbe J, Jensen CG, Dewar A, Bush A' Byrnes CA' Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children' Pediatric Pulmonolo gy 2005 ; 39: 238-246' Presentations and published abstracts from this research and related to this research: o Edwards EA, Douglas c, Broome s, Ferguson w, Kolbe J, Byrnes cA' Exhaled nitric oxide levels in children with non-cystic fibrosis bronchiectasis in New Tnaland' European Respiratory Meeting & European Respiratory Journal 2002;38: 338s' 265
Edwards EA, Douglas C, Broome S, Jensen C, Byrnes CA. Exhaled nitric oxide (NO) and ciliary beat frequency (CBF) in normal and bronchiectatic New Zealand Children. American Thoracic Meeting & American Journal of Respiratory & Critical Care Medicine 200r;163 (5): 4854. Edwards EA, Douglas C, Broome S, Jensen C, Byrnes CA. Exhaled nitric oxide (NO) and ciliary beat frequency (CBF) in normal and bronchiectatic New Zealand Children. New TnalandPaediatric Society Meeting 2000. Young investigators award. Edwards EA, Douglas C, Broome S, Jensen C, Byrnes CA. Exhaled nitric oxide (NO) and ciliary beat frequency (CBF) in normal and bronchiectatic children. New 7*aland Thoracic Society 2000. Young investigators award. Measurements of exhaled nitric oxide in children - Australiasian Paediatric Respiratory Group 1999 - invited presentation. Byrnes. CA. Exhaled nitric oxide. National New Zealand Respiratory Meeting 1998 - invited presentation. Byrnes CA, Dinarevic S, Shinbourne EA, Bush A. Exhaled nitric oxide in normal and asthmatic children - British Paediatric Society - 1996. Other Publications: Byrnes C. Non cystic fibrosis bronchiectasis. Paediatric Respiratory Reviews 2A06;7 suppl 1: 5255-5257. Twiss J, Stewart AW, Byrnes CA. Longitudinal pulmonary function of childhood bronchiectasis and comparison with cystic fibrosis. Thorax 2006;61(5): 414 - 418. Thomson JM, Wesley A, Byrnes CA, Nixon GM. Pulse intravenous methylprednisolone for resistant allergic bronchopulmonary aspergillosis in cystic fibrosis. Pediatric Pulmonolo gy 2006; 4l(2): 164-17 0. "Accreditation of Paediatric Respiratory Function Assessment Services" Dr C A Byrnes - by invitation Thoracic Society of Australia and New Zealand and Australasian Paediatric Respiratory Group. www.thoracic. org. au March 200,6. 'Wheeze and Chest infections in children less than one year of age' - Co-chairs Dr Cass Byrnes, Dr Alison Vogel. Evidence based guideline funded by a Ministry of Health initiative. Guidelines endorsed by the Paediatric Society of New 7*aland, New Zealand Guidelines Group, the Royal New Zealand College of General Practitioners and the Royal Australasian College of Physicians. www.paediatrics.org.nz. April 2005. 266
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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
Page 237 and 238: to settle. We may have been measuri
Page 239 and 240: 9.5 Off-line measurement NO determi
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Page 243 and 244: 9.6 Nasal nitric oxide measurement
Page 245 and 246: measured over two 24 hour periods,
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Page 249 and 250: While these cross-sectional and the
Page 251 and 252: symptoms. Steroid response was sign
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Page 255 and 256: season and then reduced down to bas
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Page 259 and 260: Ciabattoni et al. 2004; Petersen, A
Page 261 and 262: FEV9.5, symptom score and airways r
Page 263 and 264: Indomethacin - This medication alte
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Page 267 and 268: This low NO occurs despite higher t
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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
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Page 285 and 286: Chapter 10: Reflections The outcome
Page 287: and I enrolled 52 asthmatic childre
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 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
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Li, X. and J. W. Wilson (1997). "In
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Lymar, S. V. and J. K. Hurst (1996)
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Massaro, A. F., S. Mehta, et al. (1
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Miyabara, Y., R. Yanagisawa, et al.
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contribute to impaired endothelium-
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ODell, T. J., R. D. Hawkins, et al.
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Panza, J. A., C. E. Garcia, et al.
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Peters, S. P. (2006). "Safety of in
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Prieto, L., L. Bruno, et al. (2003)
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Ribbons, K. A., X. J. Zhang, et al.
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Sacco, O., R. Sale, et al. (2003).
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Sessa, W. C., K. Pritchard, et al.
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Silvestri, M., F. Sabatini, et al.
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Stamler, J. S. (1994). "Redox signa
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Stuehr, D. J., N. S. Kwon, et al. (
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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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