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395 results on '"Callaghan, C."'

2. Mechanisms of tolerance in a rat model of antibody-mediated allograft rejection

Author

Callaghan, C. J.

Subjects
616.079
Abstract

This thesis tests the hypothesis that Tregs with indirect allospecificity can prevent humoral rejection. Anti-CD4 monoclonal antibody and PVG.R8 donor-specific blood transfusion (DST) given pre-transplant led to long-term PVG.R8 heart graft survival in two-thirds of PVG.RT1u recipients. Alloantibody production was abrogated in these animals and tolerance was allospecific. Histology of long-term surviving grafts showed no evidence of chronic rejection. Naïve syngeneic spenocytes injected into tolerant PVG.RT1u animals did not effect heart graft rejection, suggesting the presence of regulatory mechanisms. Adoptive transfer experiments into CD4+ T cell-reconstituted congenitally athymic PVG.RT1u rats confirmed that regulation in tolerant animals was mediated by spenic CD4+ T cells. These CD4+ Tregs were allospecific. Other mechanisms of tolerance in this model were explored by breaking regulation in tolerant rats, either by immunising with immunodominant linear allopeptide, or by depleting tolerant CD4+ T cells with anti-CD4 monoclonal antibody. Surprisingly, this resulted in neither alloantibody generation nor graft rejection, suggesting that tolerance also resides within alloantigen-specific B cells. These results demonstrated that anti-CD4 + DST treatments results in the development of CD4+ Tregs that recognise alloantigen via the indirect pathway and act in an antigen-specific manner to prevent alloantibody-mediated rejection. Their development is associated with intrinsic tolerance within the alloantigen-specific B cell component that persists after CD4+ T cell help has been made available. These findings may be of use in designing clinically-applicable tolerogenic strategies in the future.

Published
2007

5. O004 Impact of normothermic regional perfusion on recipient outcomes after simultaneous pancreas and kidney transplantation – a UK analysis from the NHSBT Pancreas Advisory Group

Author

Owen, R, primary, Counter, C, additional, Tingle, S, additional, Simmonds, L, additional, Callaghan, C, additional, Casey, J, additional, Currie, I, additional, Drage, M, additional, Elker, D, additional, Manas, D, additional, Muthusamy, A, additional, Oniscu, G, additional, Pettigrew, G, additional, Sinha, S, additional, Sutherland, A, additional, Van Dellen, D, additional, Watson, C, additional, Wilson, C, additional, and White, S, additional

Published
2023
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11. O007 Pancreas and islet transplantation in the United Kingdom during the COVID-19 era

Author

Counter, C, primary, Owen, R, additional, Sinha, S, additional, Muthusamy, A, additional, Drage, M, additional, Callaghan, C, additional, Elker, D, additional, Harper, S, additional, Sutherland, A, additional, Van Dellen, D, additional, Johnson, P, additional, Manas, D, additional, Shaw, J, additional, Forsythe, J, additional, Wilson, C, additional, Hughes, S, additional, Casey, J, additional, and White, S, additional

Published
2022
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20. BSHI/BTS guidance on crossmatching before deceased donor kidney transplantation

Author

Peacock, S., primary, Briggs, D., additional, Barnardo, M., additional, Battle, R., additional, Brookes, P., additional, Callaghan, C., additional, Clark, B., additional, Collins, C., additional, Day, S., additional, Diaz Burlinson, N., additional, Dunn, P., additional, Fernando, R., additional, Fuggle, S., additional, Harmer, A., additional, Kallon, D., additional, Keegan, D., additional, Key, T., additional, Lawson, E., additional, Lloyd, S., additional, Martin, J., additional, McCaughan, J., additional, Middleton, D., additional, Partheniou, F., additional, Poles, A., additional, Rees, T., additional, Sage, D., additional, Santos‐Nunez, E., additional, Shaw, O., additional, Willicombe, M., additional, and Worthington, J., additional

Published
2021
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27. Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma

Author

Wallace, D, Cowling, TE, Walker, K, Suddle, A, Gimson, A, Rowe, I, Callaghan, C, Sapisochin, G, Mehta, N, Heaton, N, and van der Meulen, J

Abstract

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

Published
2020

28. Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK

Author

Wallace, D, Cowling, TE, Walker, K, Suddle, A, Rowe, I, Callaghan, C, Gimson, A, Bernal, W, Heaton, N, and van der Meulen, J

Abstract

BACKGROUND: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. METHODS: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. RESULTS: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). CONCLUSION: In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

Published
2020

33. Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17

Author

Vickers, M. M., Karapetis, C. S., Tu, D., OʼCallaghan, C. J., Price, T. J., Tebbutt, N. C., Van Hazel, G., Shapiro, J. D., Pavlakis, N., Gibbs, P., Blondal, J., Lee, U., Meharchand, J. M., Burkes, R. L., Rubin, S. H., Simes, J., Zalcberg, J. R., Moore, M. J., Zhu, L., and Jonker, D. J.

Published
2013
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