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252. PARENTS 2 study: consensus report for parental engagement in the perinatal mortality review process

Author

Bakhbakhi, D, Siassakos, D, Lynch, M, Timlin, L, Storey, C, Heazell, A, Burden, C, Parents Collaborative Group, Redshaw, M, Bevan, C, Kurinczuk, J, Redshaw, M, Bevan, C, and Kurinczuk, J

Subjects
Male, Parents, Consensus, Delphi Technique, Attitude of Health Personnel, Health Personnel, Perinatal Death, Delphi method, perinatal mortality review process, Computer-assisted web interviewing, Likert scale, Patient safety, parental engagement, Obstetrics and gynaecology, Stakeholder Participation, Surveys and Questionnaires, patient safety, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Grading (education), Perinatal Mortality, Medical education, Original Paper, neonatal death, Radiological and Ultrasound Technology, business.industry, Communication, Infant, Newborn, Obstetrics and Gynecology, General Medicine, Focus Groups, Stillbirth, Focus group, Original Papers, United Kingdom, healthcare improvement, Reproductive Medicine, Content analysis, perinatal death, stillbirth, Female, business
Abstract

OBJECTIVES:Following a perinatal death, a standardised multidisciplinary review should take place. Learning from these deaths and engaging parents in this process could help prevent future perinatal deaths in line with United Kingdom (UK) national and international targets to reduce the number of such deaths by 2020. Moreover, it would support parents in understanding events around the death of their baby. An earlier study (Parents' Active Role and ENgagement in The review of their Stillbirth/perinatal death - PARENTS 1 study) found that parents would endorse the opportunity to give feedback into the perinatal mortality review process (PNMR). In subsequent focus groups, healthcare professionals were positive about parental engagement, although they considered there may be significant challenges. The objective of this study was to develop core principles and recommendations for parental engagement in PNMR in the UK.METHODS:We followed a two-round Delphi technique to reach a consensus on core principles; including a national consensus workshop and an online questionnaire. The consensus meeting was attended by a national panel of stakeholders (clinical and academic experts, parent support groups, managers and commissioners) in stillbirth, neonatal and bereavement care (n=22). To develop recommendations for parental engagement, participants discussed four key areas including: receiving feedback from parents; format of the PNMR meeting; the parental pathway; and challenging aspects of engaging with parents in reviews. Content analysis was conducted to generate recommendations from the meeting for a subsequent, anonymous web-based survey. Attendees of the consensus workshop and members of the PARENTS 2 Project Advisory Board were asked to rank recommendations using a 9-point Likert scale from 1 (not important) to 9 (critical). It had been agreed a priori, in compliance with established Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, that 'Consensus' would be achieved if over 70% scored the principle as 'critical' (score 7 to 9) and less than 15% scored the principle as 'not important' (score 1 to 3). Principles where Consensus was achieved would be included in the core recommendations.RESULTS:Twenty-five of the 29 invited stakeholders participated in the consensus meeting and the subsequent online questionnaire in June 2017 (86.2% response rate). Consensus was agreed on 12 core principles. Ninety-six percent agreed that it was of critical importance that there should be a face-to-face explanation of the PNMR process; 72% considered parents should be offered the opportunity to nominate a suitable advocate; 92% believed responses to parents' comments should be formally documented; 96% indicated that it was vital for action plans to be translated into lessons learnt and that this process is monitored; and 100% of stakeholders voted that a plain English summary should be produced for the parents following the meeting. There was good agreement on a further seven principles.CONCLUSIONS:Key national stakeholders were unanimously supportive of parental engagement and agreed on core principles to make it feasible, meaningful and robust process. A six-month pilot of parental engagement in the perinatal mortality review process (PARENTS 2 Study) in two UK units took place after the consensus on core principles. In collaboration with the National Perinatal Epidemiology Unit, findings will inform the national standardised perinatal mortality review tool (PMRT).

Published
2019

253. Precise removal of Calm1 long 3′ UTR isoform by CRISPR-Cas9 genome editing impairs dorsal root ganglion development in mice

Author

Grant S. Mastick, Oliver D, Wei Yan, Lynch M, Pedro Miura, Hannah N. Gruner, Bongmin Bae, and Kevin So

Subjects
Untranslated region, Axon Fasciculation, Gene isoform, 0303 health sciences, Polyadenylation, Three prime untranslated region, Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Dorsal root ganglion, medicine, Gene, Neural development, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Most mammalian genes are subject to Alternative cleavage and PolyAdenylation (APA), often resulting in alternative length 3′ UTR isoforms. Thousands of extended or long 3′ UTR variants are preferentially expressed in neuron-enriched tissues of metazoans. However, thein vivofunctions of these long 3′ UTR isoforms are largely unknown.Calmodulin 1(Calm1)is a key integrator of calcium signaling that is required for correct neural development.Calm1generates short (Calm1-S) and long 3′ UTR (Calm1-L) mRNA isoforms via APA. We foundCalm1-Sto be broadly expressed across mouse tissues, whereasCalm1-Lexpression was largely restricted to neural tissues, including the dorsal root ganglion (DRG). Using CRISPR-Cas9 genome editing, a series of mouse deletion lines were generated that successfully eliminated expression ofCalm1-Lwhile maintaining expression ofCalm1-S. One of these lines,Calm1Δ3′ UTR, carried a 163 bp deletion surrounding the distal polyA site. Examination ofCalm1Δ3′ UTRembryos revealed disrupted development of the DRG. InCalm1Δ3′ UTRDRG explant cultures undergoing axon outgrowth, we observed a dramatic increase in axon fasciculation. These results demonstrate a physiological role forCalm1-Lin DRG development, and more generally, establish a genome-editing strategy to studyin vivofunctions of long 3′ UTR isoforms.Author SummaryMore than half of all human genes generate alternative mRNA isoforms which differ in the length of their 3’ Untranslated regions (3’ UTRs). Through a process called Alternative Cleavage and Polyadenylation thousands of broadly expressed genes preferentially express long 3’ UTR variants in brain tissues whereas their short 3’ UTR counterparts are more broadly expressed. A challenge to study the functions of these transcripts has been to generate loss of function mutant animals that lack a long 3’ UTR isoform but maintain expression of the corresponding short 3’ UTR isoform. Here, we used the precise, rapid, and efficient approach of CRISPR genome-editing to generate long 3’ UTR mutant mice. These mice, which do not express the long 3’ UTR of theCalmodulin 1(Calm1) gene, exhibit impairment in the development of sensory neurons, including increased fasciculation of axons and aberrant cell body migration. This finding is important because it provides conclusive genetic evidence for a neural function of a long 3’ UTR isoform in an animal. The CRISPR genome-editing approach used here can be applied to the study of neuron-enriched long 3’ UTR isoforms, which number in the thousands and have largely unexplored functions.

Published
2019
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256. Royal Academy of Medicine in Ireland Section of Surgery: Proceedings of registrars prize meeting held 28th april 1995 at the Royal College of Surgeons in Ireland.

Author

O’Boyle, C. J., Curran, C., Canney, M., Boyle, T. J., Maher, D., Given, H. F., Da Costa, M. L., Flynn, M., Redmond, H. P., Bouchier-Hayes, D., Keegan, D. J., Stokes, K. Y., Kelly, C. J., Hickey, D., Bouchier-Hayes, D. J., Buckley, D. J., Chapman, M. A., Durrant, L. G., Robins, R. A., Armitage, N. C., Carroll, T. A., Alyusuf, R., Regan, M. C., Greene, D., Curran, B., Kay, E., Leader, M., Fitzpatrick, J. M., Barry, M. K., Young, L. S., Regan, M. C., Geraghty, J. G., Gorey, T. F., Kelly, J. L., O’Riordain, D. S., Jones, E., O’Riordain, M. G., Kirwan, W. O., Beirne, J. C., Vaughan, F. D., Rogers., S. N., Cronin, K. J., O’Donaghue, J., Sullivan, T., Darmanin, F. X., McCann, J., O’Sullivan, S. T., Lederer, J. A., Chin, D. H. L., Horgan, A. F., Rodrick, M. L., Mannick, J. A., Lyons, A., O’Riordan, M. G., Lynch, M., O’Riordan, D. S., Hanlon, D. M. O’, Kerin, M. J., O’Donohoe, M., Byrne, J., Courtney, D. F., Quill, D. S., Fulton, J., Davies, G., and Hagen, P.

Published
1996
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262. Charge accumulation in GaAs/AlGaAs triple barrier resonant tunneling structures

Author

Buckle, P.D., Dawson, P., Kuo, C.Y., Roberts, A.H., Truscott, W.S., Lynch, M., and Missous, M.

Subjects
Photoluminescence -- Research, Quantum wells -- Research, Tunneling (Physics) -- Research, Physics
Abstract

A study was conducted on charge accumulation in three GaAs/AlGaAs triple barrier resonant tunneling structures using photoluminescence and photoluminescence excitation spectroscopy data. Results show that the charging behavior is highly asymmetrical and that the asymmetry is similar to that of double barrier resonant tunneling structures. A negatively charged exciton formation was also observed in one of the quantum wells.

Published
1998

269. National Scientific Medical Meeting 1994 Abstracts

Author

Carson, K. D., Grimes, S. B., McGinley, J. M., Thornton, M. T., Mulhall, J., Bourke, A. M., McCrory, C., Marsh, B., Hone, R., Phelan, D., White, M., Fabry, J., Hughes, D., Carson, K., Donnelly, M., Shanahan, E., Fitzpatrick, G. J., Bourke, M., Warde, D., Buggy, D., Hughes, N., Taylor, A., Dowd, N., Markham, T., Blunnie, W., Nicholson, G., O’Leary, E., Cunningham, A. J., Dwyer, R., McMechan, S., Cullen, C., Dempsey, G., Wright, G., MacKenzie, G., Anderson, J., Adgey, J., Walsh, M., O’Callaghan, P., Graham, I., O’Hare, J. A., Geoghegan, M., Iman, N., Shah, P., Chander, R., Lavin, F., Daly, K., Johnston, P. W., Imam, Z., Adgey, A. A. J., Rusk, R. A., Richardson, S. G., Hale, A., Kinsella, B. M., FitzGerald, G. A., King, G., Crean, P., Gearty, G., Cawley, T., Docherty, J. R., Geraghty, J., Osborne, H., Upton, J., D’Arcy, G., Stinson, J., Cooke, T., Colgan, M. P., Hall, M., Tyrrell, J., Gaffney, K., Grouden, M., Moore, D. J., Shanik, G., Feely, J., Delanty, N., Reilly, M., Lawson, J. A., Fitzgerald, D. J., Reilly, M. P., McAdam, B. F., Bergin, C., Walshe, M. J., Herity, N. A., Allen, J. D., Silke, B., Singh, H. P., O’Neill, S., Hargrove, M., Coleman, E., Shorten, E., Aherne, T., Kelly, B. E., Hill, D. H., McIlrath, E., Morrow, B. C., Lavery, G. G., Blackwood, B., Fee, J. P. H., Kevin, L., Doran, M., Tansey, D., Boylan, I., McShane, A. J., O’Reilly, G., Tuohy, B., Grainger, P., Larkin, T., Mahady, J., Malone, J., Condon, C., Donoghue, T., O’Leary, J., Lyons, J. F., Tay, Y. K., Tham, S. N., Khoo Tan, H. S., Gibson, G., O’Grady, A., Leader, M., Walshe, J., Carmody, M., Donohoe, J., Murphy, G. M., O’Connor, W., Barnes, L., Watson, R., Darby, C., O’Moore, R., Mulcahy, F., O’Toole, E., O’Briain, D. S., Young, M. M., Buckley, D., Healy, E., Rogers, S., Ni Scannlain, N., McKenna, M. J., McBrinn, Y., Murray, B., Freaney, R., Barrett, E., Razza, Q., Abuaisha, F., Powell, D., Murray, T. M., Powell, A. M., O’Mongain, E., O’Neill, J., Kernan, R. P., O’Connor, P., Clarke, D., Fearon, U., Cunningham, S. K., McKenna, T. J., Hayes, F., Heffernan, A., Sheahan, K., Harper, R., Johnston, G. D., Atkinson, A. B., Sheridan, B., Bell, P. M., Heaney, A. P., Loughrey, G., McCance, D. R., Hadden, D. R., Kennedy, A. L., McNamara, P., O’Shaughnessy, C., Loughrey, H. C., Reid, I., Teahan, S., Caldwell, M., Walsh, T. N., McSweeney, J., Hennessy, T. P., Caldwell, M. T. P., Byrne, P. J., Hennessy, T. P. J., El-Magbri, A. A., Stevens, F. M., O’Sullivan, R., McCarthy, C. F., Laundon, J., Heneghan, M. A., Kearns, M., Goulding, J., Egan, E. L., McMahon, B. P., Hegarty, F., Malone, J. F., Merriman, R., MacMathuna, P., Crowe, J., Lennon, J., White, P., Clarke, E., Prabhakar, M. C., Ryan, E., Graham, D., Yeoh, P. L., Kelly, P., McKeogh, D., O’Keane, C., Kitching, A., Mulligan, E., Gorey, T. F., Mahmud, N., O’Connell, M., Goggins, M., Keeling, P. W. N., Weir, D. G., Kelleher, D., McDonald, G. S. A., Maguire, D., O’Sullivan, G., Harvey, B., Cherukuri, A., McGrath, J. P., Timon, C., Lawlor, P., O’Shea, J., Buckley, M., English, L., Walsh, T., O’Morain, C., Lavelle, S. M., Kanagaratnam, B., Harding, B., Murphy, B., Kavanagh, J., Kerr, D., Lavelle, E., O’Gorman, T., Liston, S., Fitzpatrick, C., Fitzpatrick, P., Turner, M., Murphy, A. W., Cafferty, D., Dowling, J., Bury, G., Kaf Al-Ghazal, S., Zimmermann, E., O’Donoghue, J., McCann, J., Sheehan, C., Boissel, L., Lynch, M., Cryan, B., Fanning, S., O’Meara, D., Fennell, J., Byrne, P. M., Lyons, D., Mulcahy, R., Pooransingh, A., Walsh, J. B., Coakley, D., O’Neill, D., Ryall, N., Connolly, P., Namushi, R., Lawler, M., Locasciulli, A., Bacigalupo, A., Humphries, P., McCann, S. R., Pamphilon, D., Reidy, M., Madden, M., Finch, T., Borton, M., Barnes, C. A., Lawlor, S. E., Gardiner, N., Egan, L. J., Orren, A., Doherty, J., Curran, C., O’Hanlon, D., Kent, P., Kerin, M., Maher, D., Given, H. F., Lynch, S., McManus, R., O’Farrelly, C., Madrigal, L., Feighery, C., O’Donoghue, D., Whelan, C. A., Rea, I. M., Stewart, M., Campbell, P., Alexander, H. D., Crockard, A. D., Morris, T. C. M., Maguire, H., Davidson, F., Kaminski, G. Z., Butler, K., Hillary, I. B., Parfrey, N. A., Crowley, B., McCreary, C., Keane, C., O’Reilly, M., Goh, J., Kennedy, M., Fitzgerald, M., Scott, T., Murphy, S., Hildebrand, J., Holliman, R., Smith, C., Kengasu, K., Riain, U. Ni, Cormican, M., Flynn, J., Glennon, M., Smith, T., Whyte, D., Keane, C. T., Barry, T., Noone, D., Maher, M., Dawson, M., Gilmartin, J. J., Gannon, F., Eljamel, M. S., Allcut, D., Pidgeon, C. N., Phillips, J., Rawluk, D., Young, S., Toland, J., Deveney, A. M., Waddington, J. L., O’Brien, D. P., Hickey, A., Maguire, E., Phillips, J. P., Al-Ansari, N., Cunney, R., Smyth, E., Sharif, S., Eljamel, M., Pidgeon, C., Maguire, E. A., Burke, E. T., Staunton, H., O’Riordan, J. I., Hutchinson, M., Norton, M., McGeeney, B., O’Connor, M., Redmond, J. M. T., Feely, S., Boyle, G., McAuliffe, F., Foley, M., Kelehan, P., Murphy, J., Greene, R. A., Higgins, J., Darling, M., Byrne, P., Kondaveeti, U., Gordon, A. C., Hennelly, B., Woods, T., Harrison, R. F., Geary, M., Sutherst, J. R., Turner, M. J., DeLancey, J. O. L, Donnelly, V. S., O’Connell, P. R., O’Herlihy, C., Barry-Kinsella, C., Sharma, S. C., Drury, L., Lewis, S., Stratton, J., Ni Scanaill, S., Stuart, B., Hickey, K., Coulter-Smith, S., Moloney, A., Robson, M. S., Murphy, M., Keane, D., Stronge, J., Boylan, P., Gonsalves, R., Blankson, S., McGuinness, E., Sheppard, B., Bonnar, J., MacDonagh-White, C. M., Kelleher, C. C., Newell, J., White, O., Young, Y., Hallahan, C., Carroll, K., Tipton, K., McDermott, E. W., Reynolds, J. V., Nolan, N., McCann, A., Rafferty, R., Sweeney, P., Carney, D., O’Higgins, N. J., Duffy, M. J., Grimes, H., Gallagher, S., O’Hanlon, D. M., Strattan, J., Lenehan, P., Robson, M., Cusack, Y. A., O’Riordain, D., Mercer, P. M., Smyth, P. P. A., Gallagher, H. J., Moule, B., Cooke, T. G., McArdle, C. S., Burke, C., Vance, A., Saidtéar, C., Early, A., Eustace, P., Maguire, L., Cullinane, A. B. P., Prosser, E. S., Coca-Prados, M., Harvey, B. J., Saidléar, C., Orwa, S., Fitzsimons, R. B., Bradley, O., Hogan, M., Zimmerman, L., Wang, J., Kuliszewski, M., Liu, J., Post, M., Premkumar, Conran, M. J., Nolan, G., Duff, D., Oslizlok, P., Denham, B., O’Connell, P. A, Birthistle, K., Hitchcock, R., Carrington, D., Calvert, S., Holmes, K., Smith, D. F., Hetherton, A. M., Mott, M. G., Oakhill, A., Foreman, N., Foot, A., Dixon, J., Walsh, S., Mortimer, G., O’Sullivan, C., Kilgallen, C. M., Sweeney, E. C., Brayden, D. J., Kelly, J. G., McCormack, P. M. E., Hayes, C., Johnson, Z., Dack, P., Hosseini, J., O’Connell, T., Hemeryck, L., Condren, L., McCormack, P., McAdam, B., Lawson, J., Keimowitz, R., O’Leary, A., Pilkington, R., Adebayo, G. I., Gaffney, P., McGettigan, P., McManus, J., O’Shea, B., Wen, Y., Killalea, S., Golden, J., Swanwick, G., Clare, A. W., Mulvany, F., Byrne, M., O’Callaghan, E., Byrne, H., Cannon, N., Kinsella, T., Cassidy, B., Shepard, N., Horgan, R., Larkin, C., Cotter, D., Coffey, V. P., Sham, P. C., Murray, L. H., Lane, A., Kinsella, A., Murphy, P., Colgan, K., Sloan, D., Gilligan, P., McEnri, J., Ennis, J. T., Stack, J., Corcoran, E., Walsh, D., Thornton, L., Temperley, I., Lawlor, E., Tobin, A., Hillary, I., Nelson, H. G., Martin, M., Ryan, F. M., Christie, M. A., Murray, D., Keane, E., Holmes, E., Hollyer, J., Strangeways, J., Foster, P., Stanwell-Smith, R., Griffin, E., Conlon, T., Hayes, E., Clarke, T., Fogarty, J., Moloney, A. C., Killeen, P., Farrell, S., Clancy, L., Hynes, M., Conlon, C., Foley-Nolan, C., Shelley, E., Collins, C., McNamara, E., Hayes, B., Creamer, E., LaFoy, M., Costigan, P., Al fnAnsari, N., Cunney, R. J., Smyth, E. G., Johnson, H., McQuoid, G., Gilmer, B., Browne, G., Keogh, J. A. B., Jefferson, A, Smith, M., Hennessy, S., Burke, C. M., Sreenan, S., Power, C. K., Pathmakanthan, S., Poulter, L. W., Chan, A., Sheehan, M., Maguire, M., O’Connor, C. M., FitzGerald, M. X., Southey, A., Costello, C. M., McQuaid, K., Urbach, V., Thomas, S., Horwitz, E. R., Mulherin, D., FitzGerald, O., Bresnihan, B., Kirk, G., Veale, D. J., Belch, J. J. F., Mofidi, A., Mofidi, R., Quigley, C., McLaren, M., Veale, D., D’Arrigo, C., Couto, J. Candal, Woof, J., Greer, M., Cree, I., Belch, J., Hone, S., Fenton, J., Hamilton, S., and McShane, D.

Published
1994
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270. Irish society for rheumatology: Proceedings of annual general meeting held in Beaumont Hospital on Friday 22nd October, 1993

Author

Mulherin, Diarmuid, FitzGerald, Oliver, Bresnihan, Barry, Bruce, I. N., McNally, J. A., Bell, A. L., Yanni, G., Cauli, A., Challacombe, S., Panayi, G. S., Foley-Nolan, D., Akil, M., Anthony, M., Cundall, D., Bourne, J., Arthur, R., Chamberlain, M. A., Byrne, P., Mahon, N., Robinson, H., Sant, S. M., Donnelly, S., Barnes, L., Watson, R., Casey, E. B., Donnelly, S., Casey, E. B., Bruce, I. N., Edgar, D. E., McMillan, S. A., Conlan, S. K., McNeill, T. A., Bell, A. L., Robinson, H., Byrne, P., Mahon, N., Sant, S. M., Abuzakouk, M., Feighery, C., Jones, E., O’Briain, S., Goggins, M., Weir, D. G., Casey, E., O’Farrelly, C., Kelleher, D., Murphy, A., Casey, E. B., Veale, D. J., Kirk, G., McLaren, M., Belch, J. J. F., Byrne, P., Mahon, N., Robinson, H., Sant, S. M., Foley-Nolan, D., Daly, M. J., Mahon, N., Robinson, H., Byrne, P., Sant, S. M., Donnelly, S., Murphy, J., Lynch, M., Casey, E. B., McKernan, S., Donnelly, S., Casey, E. B., Sothinathan, R., Donnelly, S., Casey, E. B., Blake, C., Garrett, M., Robinson, H., Byrne, P., Mahon, N., Sant, S. M., Gourley, I. S., Bell, A. L., Bresnihan, B., FitzGerald, O., Cunnane, G., Abuzakouk, M., Feighery, C., Bergin, C., Cherukuri, A., Weir, D. G., Casey, E., O’Farrelly, C., Mulherin, D., Kirk, G., Veale, D. J., Belch, J. J. F., Bresnihan, B., FitzGerald, O., Kelleher, D., Hall, N., Murphy, A., Casey, E. B., Mulcahy, B., Molloy, M., Phelan, M., O’Gara, F., McConnell, F., Shanahan, F., FitzGerald, O., Heffernan, M., Mulcahy, B., Neary, P., and Molloy, M.

Published
1994
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272. Mice, men, mustards and methylated xanthines: the potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents

Author

Byfield, JE, Murnane, J, Ward, JF, Calabro-Jones, P, Lynch, M, and Kulhanian, F

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Alkylating Agents, Animals, Caffeine, Cell Survival, Cells, Cultured, Cyclophosphamide, DNA Repair, DNA Replication, DNA, Neoplasm, HeLa Cells, Humans, Melphalan, Mice, Neoplasms, Experimental, Rats, Ultraviolet Rays, Xanthines, Hela Cells, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

The relationships between DNA damage from UV radiation, alkylating drugs and the methylated xanthines (MX) have been studied in normal and malignant rodent and human cells. A comparison of the level of DNA excision repair (repair replication and unscheduled DNA synthesis) confirms that some forms of alkylating-agent damage (probably mono-filar DNA adducts) are less completely removed by both normal and malignant rodent cells than by their human counterparts, rendering rodent cells more susceptible to the toxic potential of unexcised lesions. The toxicity of alkylating agents can be increased by the presence of several MXs during the period of DNA replication which follows infliction of the damage. Human cells appear capable of excising more DNA damage, rendering them somewhat less susceptible to enhancement of cytotoxicity by MX. This resistance of human cells is only quantitative, however, since 2 human cancer cell lines (HeLa and HT-29) could be sensitized to a variety of alkylating agents by appropriate concentrations of MX. Trimethylxanthine (caffeine) and the 2 clinically useful dimethylxanthines (theophylline and theobromine) appeared equally effective in sensitizing cells. The sensitization was dependent upon a slightly cytotoxic concentration of the MX and a suitably prolonged period of post-damage MX exposure. Of these 3 classic MXs, only theobromine might be clinically useful. The levels required for alkylating-agent sensitization exceed the clinically tolerable level of theophylline, and probably approach the tolerance of man to caffeine. The most likely mechanism by which MX sensitization is achieved is reversal of the inhibition of DNA replicon initiation which follows the infliction of significant DNA damage. Through the selection of suitable clinically useful alkylating agents (those dependent on active cellular transport for cell penetration) and appropriate MX scheduling, an enhanced therapeutic ratio might be achieved, potentially increasing the clinical usefulness of these alkylating agents. MX would thus form a useful class of agents adjuvant to conventional anti-cancer drugs.

Published
1981

275. Irish society of gastroenterology: Proceedings of Winter Meeting held 4th/5th December 1992in Beaumont hospital, Dublin

Author

O’Sullivan, M., Thornton, G., O’Sullivan, G., O’Mahony, A. M., O’Connell, J., Hanvajanawong, C., Phelan, D., O’Sullivan, G. C., Collins, J. K., Bamford, K. B., Lutton, D. A., Collins, J. S. A., O’Loughlin, B., Johnston, B. T., McFarland, R. J., Love, A. H. G., Buchanan, K. D., Fillmore, D., Ardill, J. E. S., Clyne, M., Drumm, B., Cyne, M., Tham, T. C. K., McLaughlin, N., Hughes, D. F., Ferguson, M., Crosbie, J. J., Madden, M., Namnyak, S., O’Connor, F. A., Magbri, Awad El, Stevens, F. M., McCarthy, C. F., Lynch, M., O’Brien, M., Ryan, E., MacMathuna, P., Kelly, P., Lennon, J., Crowe, J., Mulvey, S., Maguire, C., Clarke, E., Cronin, K. J., Kent, P., Mooney, E., Corrigan, T., O’Connell, R., Fitzpatrick, J. M., Gorey, T. F., Prabhaker, M. C., Bannon, C. A., Delaney, C., Duggan, M., Gorey, T., Abuzakouk, M., Lynch, S., Casey, E., Weir, D., Feighery, C., O’Farrelly, C., Fan, X. J., Chua, A., Shahi, C. N., Kelleher, D., Keeling, P. W. N., Parks, R. W., Diamond, T., McCrory, D. C., Johnston, G. W., Clements, W. D. B., Ennis, M., Campbell, G. R., Halliday, M. I., Rowlands, B. J., Wilson, R. H., Williamson, K., McLoughlin, J., Moorehead, R. J., O’Connor, A. M., Johnston, C. F., Gillmore, D., Boreham, C., Caldwell, M. T. P., Jazrawi, S., Byrne, P. J., Walsh, T. N., Hennessy, T. P. J., Li, H., Kay, E. W., Mulcahy, H., Curran, B., O’Donoghue, D., Leader, M., Walsh, C. Barry, O’Sullivan, S. T., Reardon, C. M., Hardiman, C., O’Donnell, J. A., Kirwan, W. O., Brady, M. P., McGreal, G., Hehir, D. J., Brady, M. P., O’Donnell, J., Pender, S. M., Courtney, M. G., Fielding, J. F., Swan, N., Chong, A., Denesh, T. G., Coll, D., McElearney, C., Kay, E., Sant, S., Doyle, J. S., Buckley, M., Cahill, R. J., Beattie, S., Hamilton, H., O’Morain, C., O’Sullivan, K., Forde, A. M., Gilvarry, J., Jackson, J., Alvi, R., Leahy, A., Lynch, G., Lane, B., Browne, H. Y., Keeling, P., Stafford-Johnson, D., Kee, S., Carr, J., Ryan, M. J., Sheehan, S., Broe, P., Deasy, J., O’Donovan, D. A., Bouchier-Hayes, D. M., Kelly, C., Grace, P., Redmond, H. P, Burke, P., Bouchier-Hayes, D. J., O’Malley, K., Qureshi, A., Osborne, H., Monkhouse, W. S., Bouchier-Hayes, D., Goggin, M., Joyce, W. P., Traynor, O., Hyland, J., Beausang, E., Mealy, K., Prendergast, C., Joyce, L., McNicholas, M. M. J., Gibney, R. G., Dolan, J., MacErlean, D. P., Hyland, J. M., Fenlon, H. M., Mulcahy, H. E., Stack, W. A., Skelly, M. M., Hegarty, J. E., Stack, W., O’Donoghue, D. P., Norris, S. M., McNicholas, M., Murray, F. E., Williams, N., Burke, J., Lamort, W., Fitzpatrick, J., Afdhal, N., Gibney, R., McLoughlin, R. F., Mourad, F. H., O’Donnell, L. J. D., Dias, J., Ogutu, E., Farthing, M. J. G., Hoyle, C. H. V., Hill, A. D. K., Darzi, A., Carey, P. D., Menzies-Gow, N., Monson, J. R. T., Goggins, M. G., O’Broin, S., Kelleher, B., Scott, J. M., Weir, D. D., Watson, R. G. P., Goss, B., Angus, P. W., Duckham, N., Sewell, R. B., and Smallwood, R. A.

Published
1993
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276. The Irish paediatrics association and section of paediatrics, royal academy of medicine in Ireland: Proceedings of joint meeting held May 15th & 16th, 1992 in Great Northern Hotel, Bundoran, Co. Donegal

Author

Miyakita, H., Puri, P., Zia S., Kearney P. J., Lambert, I., Browne, P., O’Brien, N., Carson, J., Temperley, I. J., Jackson, F., White, M., Beckett, M., O’Regan, M., Matthews, T., Jalees, S., McDonagh, B., McMenamin, J., Gumaa, S., Connolly, K., Egan Mitchell, B., McNicholl, B., Loftus, B. G., Kinlen, D. M., Hoey, H. M. C. V., Burke-Gaffney, A., Reen, D. J., Hill, R., Hensey, O. J., McKay, M., Hutchinson, T., Fallon, M., Kelly, M., Gorman, W., Clarke, T., Griffin, E., Matthews, T., Murphy, J., O’Brien, N., Sheridan, M., Philip, M., McCann, S., Connolly, B., O’Brien, N., King, M., Gorman, W., Hensey, O., Donoghue, V., Fahy, S., Nicholson, A., O’Keefe, M., Surana, R., O’Nuallain, E. M., Monaghan, H., Mulrane, S., Taylor, M., Tempany, E., Bourke, B., Lyons, D., McCarthy, J. F., Neligan, M. C., Wood, A. E., Murphy, A. W., Power, R., Kinlen, D., Johnson, Z., Quinn, F., Brady, R. M., Arvind, A., Healy, R., Staines, A., Bodansky, H. J., Stephenson, C., Haigh, D., Cartwright, R. A., Puri, I., O’Hagan, M., Zbaeda, M. M., Bagyaraj, A., Wall, O., O’Connell, U., Bate, T., Losty, P., Lynch, M., Guiney, E. J., Hassan, J., Gormally, S., Drumm, B., Abraham, G., Costigan, C., Fogarty, J., Moloney, A. C., Ninan, G., and Fitzgerald, R. J.

Published
1993
Full Text
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