Pub Date : 2008-08-07DOI: 10.2174/1874418400802010029
A. Mathis, D. Schiller
A potential warfarin - voriconazole interaction has been identified in one study involving healthy individuals. We report a case where addition of voriconazole possibly increased the international normalized ratio (INR) in a renal transplant patient taking warfarin. The INR elevation was resistant to reversal agents, and the situation may have ulti- mately contributed to a thrombotic episode.
{"title":"A Possible Interaction of Voriconazole and Warfarin in a Renal Transplant Recipient","authors":"A. Mathis, D. Schiller","doi":"10.2174/1874418400802010029","DOIUrl":"https://doi.org/10.2174/1874418400802010029","url":null,"abstract":"A potential warfarin - voriconazole interaction has been identified in one study involving healthy individuals. We report a case where addition of voriconazole possibly increased the international normalized ratio (INR) in a renal transplant patient taking warfarin. The INR elevation was resistant to reversal agents, and the situation may have ulti- mately contributed to a thrombotic episode.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"2 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2008-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68072015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-07-11DOI: 10.2174/1874418400802010021
I. Fuentes-Boquete, M. C.Arufe Gonda, S. M. Diaz Prado, T. Hermida Gomez, F. J. D. T. Santos, F. J. Blanco
Articular cartilage lesions that do not disrupt the integrity of subchondral bone are not capable of spontaneous repair. The asymptomatic nature of these lesions leads to articular cartilage degeneration and development of the os- teoarthritic process. To avoid joint replacement surgery, several cellular therapies have been developed. These therapies focus on the regeneration of a new tissue, whose structure, biochemistry composition and function should be the same as those of endogenous articular cartilage. Current approaches for interrupting the osteoarthritic process produce a fibrocartilaginous tissue, not articular cartilage. The implantation of autologous chondrocytes and autologous mosaicplasty induces a better quality of articular cartilage; however, both techniques damage the existing cartilage because of the need to harvest large numbers of chondrocytes or to extract an osteochondral cylinder for implantation. While stem cells are a promising tool for repairing articular carti- lage, their use is in an early experimental stage at this time. Although studies of cell therapy have shown clinical and func- tional improvement in joints, the ability to regenerate articular cartilage that resists the degeneration process remains elu- sive.
{"title":"Cell and Tissue Transplant Strategies for Joint Lesions","authors":"I. Fuentes-Boquete, M. C.Arufe Gonda, S. M. Diaz Prado, T. Hermida Gomez, F. J. D. T. Santos, F. J. Blanco","doi":"10.2174/1874418400802010021","DOIUrl":"https://doi.org/10.2174/1874418400802010021","url":null,"abstract":"Articular cartilage lesions that do not disrupt the integrity of subchondral bone are not capable of spontaneous repair. The asymptomatic nature of these lesions leads to articular cartilage degeneration and development of the os- teoarthritic process. To avoid joint replacement surgery, several cellular therapies have been developed. These therapies focus on the regeneration of a new tissue, whose structure, biochemistry composition and function should be the same as those of endogenous articular cartilage. Current approaches for interrupting the osteoarthritic process produce a fibrocartilaginous tissue, not articular cartilage. The implantation of autologous chondrocytes and autologous mosaicplasty induces a better quality of articular cartilage; however, both techniques damage the existing cartilage because of the need to harvest large numbers of chondrocytes or to extract an osteochondral cylinder for implantation. While stem cells are a promising tool for repairing articular carti- lage, their use is in an early experimental stage at this time. Although studies of cell therapy have shown clinical and func- tional improvement in joints, the ability to regenerate articular cartilage that resists the degeneration process remains elu- sive.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"2 1","pages":"21-28"},"PeriodicalIF":0.0,"publicationDate":"2008-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68072008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-06-24DOI: 10.2174/1874418400802010013
K. Goldsmith, L. Sharples, C. Sudarshan, J. Parameshwar, S. Tsui, J. Wallwork, S. Large
years of heart transplantation data were used to identify factors associated with patient survival and investi- gate changes over time. Analysis was performed across 5 time eras - pre-triple therapy, post-triple therapy to 1990 and the remaining 15 years through 2005 divided into 3 groups of 5 years each. Both short- and long-term survival improved with the advent of triple therapy, but remained unchanged from the early 1990's. Mean donor and recipient age, proportion of female donors and recipients, transplants with two human leucocyte antigen (HLA)-DR mismatches, ischaemic and car- diopulmonary bypass times (CPB) have increased, while rates of rejection and infection have decreased over time. Female donor and recipient diagnosis were independent predictors of short-term mortality. Older age, recipient diagnosis, 2 or more early rejection episodes and number of HLA-A mismatches were independent predictors of mortality in the long- term. Survival rates after heart transplantation improved with advances in patient care, but have remained static since, dur- ing which time there have been increases in risk factors and use of more marginal donors.
{"title":"Twenty-five years of heart transplantation at Papworth Hospital: Changes in factors influencing short- and long-term patient survival over time","authors":"K. Goldsmith, L. Sharples, C. Sudarshan, J. Parameshwar, S. Tsui, J. Wallwork, S. Large","doi":"10.2174/1874418400802010013","DOIUrl":"https://doi.org/10.2174/1874418400802010013","url":null,"abstract":"years of heart transplantation data were used to identify factors associated with patient survival and investi- gate changes over time. Analysis was performed across 5 time eras - pre-triple therapy, post-triple therapy to 1990 and the remaining 15 years through 2005 divided into 3 groups of 5 years each. Both short- and long-term survival improved with the advent of triple therapy, but remained unchanged from the early 1990's. Mean donor and recipient age, proportion of female donors and recipients, transplants with two human leucocyte antigen (HLA)-DR mismatches, ischaemic and car- diopulmonary bypass times (CPB) have increased, while rates of rejection and infection have decreased over time. Female donor and recipient diagnosis were independent predictors of short-term mortality. Older age, recipient diagnosis, 2 or more early rejection episodes and number of HLA-A mismatches were independent predictors of mortality in the long- term. Survival rates after heart transplantation improved with advances in patient care, but have remained static since, dur- ing which time there have been increases in risk factors and use of more marginal donors.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"2 1","pages":"13-20"},"PeriodicalIF":0.0,"publicationDate":"2008-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68071996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-05-14DOI: 10.2174/1874418400802010009
R. Ignatius, E. Zhang, Felix Schulte, M. Schroff, U. Rüschendorf, A. Müller, B. Wittig, F. Hoffmann
To study the impact of gene transfer in experimental corneal transplantation, grafts should reliably be rejected but after a time span, which allows multiple interventions. We were interested in delaying transplant survival time through MHC-matching of donor and recipient animals and in omitting local dexamethasone treatment, which is laborious and could potentially interfere with the expression of administered DNA. Rejection of DBA/2 (H-2d) corneas by BALB/c (H- 2d) recipients occurred significantly delayed compared with C3H (H-2k) grafts (25.0 ± 5.6 vs. 14.5 ± 4.1 days, p=0.038), and correlated with the expression of allospecific T cell-proliferation and IFN- secretion in draining lymph nodes. Gene gun treatment with IL-4/CTLA-4 DNA MIDGE TM vectors in the lower lid of recipients significantly prolonged survival of DBA/2 corneas in BALB/c mice. This refined and dexamethasone-free protocol may be advantageous for the develop- ment of novel treatment strategies, e.g., local gene transfer, in corneal transplantation.
为了研究基因转移对实验性角膜移植的影响，移植物应该可靠地排斥，但要经过一段时间，这允许多种干预。我们感兴趣的是通过供体和受体动物的mhc匹配来延迟移植存活时间，并省略局部地塞米松治疗，这是费力的，可能会干扰给药DNA的表达。与C3H (H-2k)相比，BALB/c (H-2d)受体对DBA/2 (H-2d)角膜的排斥反应发生明显延迟(25.0±5.6 vs 14.5±4.1天，p=0.038)，并与引流淋巴结中异体特异性T细胞增殖表达和IFN-分泌有关。受体下眼睑IL-4/CTLA-4 DNA MIDGE TM载体基因枪处理可显著延长BALB/c小鼠DBA/2角膜的生存期。这种改进的和不含地塞米松的方案可能有利于开发新的治疗策略，例如角膜移植中的局部基因转移。
{"title":"Transplantation of DBA/2 Mouse Corneas in BALB/c Recipients SignificantlyDelays Graft Rejection Compared with C3H Grafts and FacilitatesStudies on Gene Transfer","authors":"R. Ignatius, E. Zhang, Felix Schulte, M. Schroff, U. Rüschendorf, A. Müller, B. Wittig, F. Hoffmann","doi":"10.2174/1874418400802010009","DOIUrl":"https://doi.org/10.2174/1874418400802010009","url":null,"abstract":"To study the impact of gene transfer in experimental corneal transplantation, grafts should reliably be rejected but after a time span, which allows multiple interventions. We were interested in delaying transplant survival time through MHC-matching of donor and recipient animals and in omitting local dexamethasone treatment, which is laborious and could potentially interfere with the expression of administered DNA. Rejection of DBA/2 (H-2d) corneas by BALB/c (H- 2d) recipients occurred significantly delayed compared with C3H (H-2k) grafts (25.0 ± 5.6 vs. 14.5 ± 4.1 days, p=0.038), and correlated with the expression of allospecific T cell-proliferation and IFN- secretion in draining lymph nodes. Gene gun treatment with IL-4/CTLA-4 DNA MIDGE TM vectors in the lower lid of recipients significantly prolonged survival of DBA/2 corneas in BALB/c mice. This refined and dexamethasone-free protocol may be advantageous for the develop- ment of novel treatment strategies, e.g., local gene transfer, in corneal transplantation.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"2 1","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2008-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68071988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-04-16DOI: 10.2174/1874418400802010001
V. Peut, A. Rice
Background: Breast cancer kills about 400 000 people annually worldwide. Whilst the conventional therapy of surgery, radiation, chemotherapy and hormone therapy has increased survival rates dramatically, the relapse rate is intol- erably high. New therapies, particularly immunotherapies, required to combat this residual disease would ideally be tested on an animal model. Current animal models of human breast cancer available for testing new therapies are unreliable. We therefore sought to develop a protocol that will enable the reliable and reproducible production of a xenograft murine model of human breast cancer. Methods: Female NOD/SCID mice, under specific pathogen-free conditions, were inoculated subcutaneously in the ingui- nal mammary fat pad area with either dissociated primary breast tumours or the breast cancer cell line MCF7. Variables tested included irradiation of mice prior to inoculation, differing tumour cell numbers and the use of the commercial basement membrane Matrigel. Results: 100% engraftment and growth of both MCF7 cells and dissociated primary breast tumour cells, coinoculated with Matrigel, was achieved regardless of whether the mouse was irradiated or not, however larger tumour volume was achieved in the non-irradiated mice. The largest inoculum, 5 x 10 6 cells of MCF7 cells, gave the largest tumours after 3 months in situ (p=0.006). The number of cells injected from primary tumours did not correlate with final tumour size. Both MCF7 and primary human breast tumours exhibited the layered nature of breast tumours, with living cells on the pe- riphery and necrotic cells in the interior. MCF7 cells that engrafted maintained their ER+, CD24+, CD44+ BC2+ (MUC1+) status after in vivo growth. All tumours became vascularised but no metastasis was evident. Conclusions: This is a simple and reliable protocol that ensures human breast tumour growth in the NOD/SCID mouse. This model is valid, in that the tumours are orthotopic, they have the layered nature of human breast tumours, become vascularised and maintained the surface and nuclear marker status tested for. It has potential as a valid human breast can- cer test bed for preclinical testing of immunotherapies and anti-angiogenesis agents.
{"title":"A NOD/SCID Model of Primary Human Breast Cancer","authors":"V. Peut, A. Rice","doi":"10.2174/1874418400802010001","DOIUrl":"https://doi.org/10.2174/1874418400802010001","url":null,"abstract":"Background: Breast cancer kills about 400 000 people annually worldwide. Whilst the conventional therapy of surgery, radiation, chemotherapy and hormone therapy has increased survival rates dramatically, the relapse rate is intol- erably high. New therapies, particularly immunotherapies, required to combat this residual disease would ideally be tested on an animal model. Current animal models of human breast cancer available for testing new therapies are unreliable. We therefore sought to develop a protocol that will enable the reliable and reproducible production of a xenograft murine model of human breast cancer. Methods: Female NOD/SCID mice, under specific pathogen-free conditions, were inoculated subcutaneously in the ingui- nal mammary fat pad area with either dissociated primary breast tumours or the breast cancer cell line MCF7. Variables tested included irradiation of mice prior to inoculation, differing tumour cell numbers and the use of the commercial basement membrane Matrigel. Results: 100% engraftment and growth of both MCF7 cells and dissociated primary breast tumour cells, coinoculated with Matrigel, was achieved regardless of whether the mouse was irradiated or not, however larger tumour volume was achieved in the non-irradiated mice. The largest inoculum, 5 x 10 6 cells of MCF7 cells, gave the largest tumours after 3 months in situ (p=0.006). The number of cells injected from primary tumours did not correlate with final tumour size. Both MCF7 and primary human breast tumours exhibited the layered nature of breast tumours, with living cells on the pe- riphery and necrotic cells in the interior. MCF7 cells that engrafted maintained their ER+, CD24+, CD44+ BC2+ (MUC1+) status after in vivo growth. All tumours became vascularised but no metastasis was evident. Conclusions: This is a simple and reliable protocol that ensures human breast tumour growth in the NOD/SCID mouse. This model is valid, in that the tumours are orthotopic, they have the layered nature of human breast tumours, become vascularised and maintained the surface and nuclear marker status tested for. It has potential as a valid human breast can- cer test bed for preclinical testing of immunotherapies and anti-angiogenesis agents.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"2 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2008-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68071928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-12-11DOI: 10.2174/1874418400701010001
A. Amara, L. Shalamanova, Asheesh Sharma, A. Shenkin, A. Bakran, Ajay K. Sharma, A. Hammad, R. Rustom
Background: After the first year of transplantation chronic allograft nephropathy is the most important cause of renal graft loss and hypertension and proteinuria occur commonly. In native nephropathies, proteinuria and progression to renal failure are linked and renal tubulo-interstitial fibrosis determines prognosis. Monocyte chemoattractant protein-1 (MCP-1) is a powerful chemokine promoting tubulo-interstitial fibrosis but data are limited in a transplant context. Hence this observational cross-sectional study. Methods: The MAP, 24h urinary creatinine clearance, proteinuria and MCP-1 were measured in 81 renal transplant pa- tients (43 with chronic allograft nephropathy). Most patients were on calcineurin-inhibitor based immunosuppression. Re- gression analysis was applied and comparisons made with 64 patients with native nephropathies and comparable function. Results: One fifth (18/81) of all renal transplant patients had less than optimally controlled hypertension. Proteinuria was heaviest in non-transplanted patients (average 3.0 g/24h, 0.1-12.2) and the ciclosporin-treated transplant patients (1.2 g/24h, 0.02-6.4). Proteinuria and MCP-1 were positively correlated in all patients (r 0.54, p<0.0001) and r 0.84, p<0.0001 in 19 transplant patients receiving angiotensin-converting enzyme inhibitors. MCP-1 levels were highest in non-transplant and ciclosporin-treated patients; geometric mean (SE), 412.4(1.16) and 314.5(1.21) pg/24h respectively. MCP-1 levels were unrelated to age, MAP, creatinine clearance, or blood ciclosporin or tacrolimus levels. Conclusions: Urinary MCP-1 may be a useful non-invasive marker of chronic graft dysfunction in transplant patients fa- cilitating monitoring of progression and response to treatment even in proteinuric patients.
{"title":"Urinary monocyte chemoattractant protein-1 (MCP-1) in renal transplant recipients: implications in proteinuric patients","authors":"A. Amara, L. Shalamanova, Asheesh Sharma, A. Shenkin, A. Bakran, Ajay K. Sharma, A. Hammad, R. Rustom","doi":"10.2174/1874418400701010001","DOIUrl":"https://doi.org/10.2174/1874418400701010001","url":null,"abstract":"Background: After the first year of transplantation chronic allograft nephropathy is the most important cause of renal graft loss and hypertension and proteinuria occur commonly. In native nephropathies, proteinuria and progression to renal failure are linked and renal tubulo-interstitial fibrosis determines prognosis. Monocyte chemoattractant protein-1 (MCP-1) is a powerful chemokine promoting tubulo-interstitial fibrosis but data are limited in a transplant context. Hence this observational cross-sectional study. Methods: The MAP, 24h urinary creatinine clearance, proteinuria and MCP-1 were measured in 81 renal transplant pa- tients (43 with chronic allograft nephropathy). Most patients were on calcineurin-inhibitor based immunosuppression. Re- gression analysis was applied and comparisons made with 64 patients with native nephropathies and comparable function. Results: One fifth (18/81) of all renal transplant patients had less than optimally controlled hypertension. Proteinuria was heaviest in non-transplanted patients (average 3.0 g/24h, 0.1-12.2) and the ciclosporin-treated transplant patients (1.2 g/24h, 0.02-6.4). Proteinuria and MCP-1 were positively correlated in all patients (r 0.54, p<0.0001) and r 0.84, p<0.0001 in 19 transplant patients receiving angiotensin-converting enzyme inhibitors. MCP-1 levels were highest in non-transplant and ciclosporin-treated patients; geometric mean (SE), 412.4(1.16) and 314.5(1.21) pg/24h respectively. MCP-1 levels were unrelated to age, MAP, creatinine clearance, or blood ciclosporin or tacrolimus levels. Conclusions: Urinary MCP-1 may be a useful non-invasive marker of chronic graft dysfunction in transplant patients fa- cilitating monitoring of progression and response to treatment even in proteinuric patients.","PeriodicalId":90368,"journal":{"name":"The open transplantation journal","volume":"1 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2007-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68071920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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