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Camillo Ricordi - One of the best experts on this subject based on the ideXlab platform.
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Transplantation of stem cell-derived Pancreatic Islet cells
Nature Reviews Endocrinology, 2020Co-Authors: Giacomo Lanzoni, Camillo RicordiAbstract:A large fraction of patients with diabetes mellitus require insulin treatment to control glucose metabolism; however, this treatment brings risks of hypoglycaemia and provides suboptimal metabolic control. Transplantation of stem cell-derived Pancreatic Islet cells could be an ideal solution, which is approaching clinical translation.
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autologous Pancreatic Islet transplantation for severe trauma
The New England Journal of Medicine, 2010Co-Authors: Rahul M Jindal, Camillo Ricordi, Craig D ShriverAbstract:To the Editor: Autologous Pancreatic Islet transplantation has been successfully carried out after total pancreatectomy for chronic pancreatitis, and allogeneic Islet-cell transplantation has had limited success.1,2 We report a case of successful Islet transplantation from the pancreas after total pancreatectomy because of trauma. A 21-year-old airman serving in a remote part of Afghanistan was hit by three high-velocity bullets on November 21, 2009, and was rapidly transferred to Walter Reed Army Medical Center. As part of needed rescue surgery, a portion of the stomach, the gallbladder, the entire duodenum, and the head of the pancreas were removed. In addition, . . .
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Pancreatic Islet transplantation for treating diabetes
Expert Opinion on Biological Therapy, 2006Co-Authors: Shinichi Matsumoto, Yukihide Yonekawa, Hirofumi Noguchi, Naoya Kobayashi, Teru Okitsu, Yasuhiro Iwanaga, Hideo Nagata, Camillo RicordiAbstract:Pancreatic Islet transplantation is one of the options for treating diabetes and has been shown to improve the quality of life of severe diabetic patients. Since the Edmonton protocol was announced, Islet transplantation have advanced considerably, including Islet after kidney transplantation, utilisation of non-heart-beating donors, single-donor Islet transplantation and living-donor Islet transplantation. These advances were based on revised immunosuppression protocols, improved pancreas procurement and Islet isolation methods, and enhanced Islet engraftment. Further improvements are necessary to make Islet transplantation a routine clinical treatment. To synergise efforts towards a cure for type 1 diabetes, a Diabetes Research Institute (DRI) Federation is currently being established to include leading diabetes research centres worldwide, including DRIs in Miami, Edmonton and Kyoto among others.
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transaminitis after Pancreatic Islet transplantation
Journal of The American College of Surgeons, 2005Co-Authors: Neal R Barshes, Amy Mote, Paige A Schock, Sarah E. Goodpastor, Charles F Brunicardi, Rajesh Balkrishnan, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background An asymptomatic, self-limited transaminitis uniformly follows Pancreatic Islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote Pancreatic Islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the Pancreatic Islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.
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Lack of cytomegalovirus infection after Pancreatic Islet transplantation
Journal of Surgical Research, 2004Co-Authors: Neal R Barshes, Brian J. Williams, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Abstract Background. Cytomegalovirus (CMV) infection in the immunosuppressed transplant recipient is a cause of significant morbidity. With ganciclovir prophylaxis, the overall incidence of CMV after simultaneous kidney-whole pancreas transplantation remains as high as 40%, while CMV infection has never been reported following Pancreatic Islet transplantation (PIT) alone (i.e., without kidney transplantation). We designed the following study to objectively quantify the rate of transmission of CMV after clinical PIT. Methods. The 26 Pancreatic Islet grafts used at our institution since 1/2001 and the corresponding 11 PIT recipients were studied. The CMV serology of all organ donors was tested using a latex agglutination assay for anti-CMV antibody (CMV Scan™, Becton Dickinson®, Cockeysville, MD), a test capable of detecting one CMV-infected cell per 50,000 cells. Following PIT, recipients were closely monitored for clinical symptoms consistent with CMV infection. All patients were tested monthly for the presence of CMV antigenemia using immunofluorescent monoclonal antibodies for the CMV pp65 antigen (Light Diagnostics™, Chemicon®, Temecula, CA). All patients received valganciclovir 450 mg PO BID for 3 months following each PIT. Immunosuppression consisted of daclizumab, sirolimus, and tacrolimus. Results. Eight of the PIT recipients (72%) were CMV seronegative prior to PIT (R−). Eighteen of the 26 Pancreatic Islet grafts (69%) were from CMV+ donors (D+), and the remaining eight (31%) were from CMV− donors (D−). A single R− recipient received only D− Pancreatic Islets, while the remaining seven received at least one D+ Pancreatic Islets graft. In all there were 6 D+R+, 3 D−R+, 12 D+R−, and 5 D−R− PITs. No patient developed symptoms consistent with CMV infection at any time following PIT. Monthly routine blood testing of all recipients has revealed no detectable CMV antigenemia in any patient. Conclusion. In our series neither CMV transmission nor CMV infection was seen after PIT. The risk of CMV transmission is lower after PIT than the risk after simultaneous kidney--pancreas transplantation.
John A. Goss - One of the best experts on this subject based on the ideXlab platform.
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inflammation mediated dysfunction and apoptosis in Pancreatic Islet transplantation implications for intrahepatic grafts
Journal of Leukocyte Biology, 2005Co-Authors: Neal R Barshes, Samuel Wyllie, John A. GossAbstract:Recent advances in clinical protocols have improved the outcomes of Pancreatic Islet transplantation (PIT), yet PIT recipients typically require Pancreatic Islet grafts derived from multi- ple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of Pancreatic Islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involve- ment of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1 appears to be among the most important inflammatory mediators, causing pan- creatic Islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) syn- thase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the Pancreatic Islets, and depletion or inhibition of Kupffer cells improves outcomes following exper- imental PIT. Immediately after transplantation, the Pancreatic Islets are perfused only by portal vein blood until the process of angiogenesis re- stores arterial blood flow some 7-10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion mole- cules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the imme- diate post-transplant period, hepatocytes may con- tribute to Pancreatic Islet injury through the pro- duction of NO. This paper reviews literature re- garding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the patho- physiology of hepatic ischemia-reperfusion and their relation to the survival and function of intra- hepatic Pancreatic Islet grafts. J. Leukoc. Biol. 77: 000-000; 2005.
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transaminitis after Pancreatic Islet transplantation
Journal of The American College of Surgeons, 2005Co-Authors: Neal R Barshes, Amy Mote, Paige A Schock, Sarah E. Goodpastor, Charles F Brunicardi, Rajesh Balkrishnan, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background An asymptomatic, self-limited transaminitis uniformly follows Pancreatic Islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote Pancreatic Islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the Pancreatic Islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.
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Lack of cytomegalovirus infection after Pancreatic Islet transplantation
Journal of Surgical Research, 2004Co-Authors: Neal R Barshes, Brian J. Williams, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Abstract Background. Cytomegalovirus (CMV) infection in the immunosuppressed transplant recipient is a cause of significant morbidity. With ganciclovir prophylaxis, the overall incidence of CMV after simultaneous kidney-whole pancreas transplantation remains as high as 40%, while CMV infection has never been reported following Pancreatic Islet transplantation (PIT) alone (i.e., without kidney transplantation). We designed the following study to objectively quantify the rate of transmission of CMV after clinical PIT. Methods. The 26 Pancreatic Islet grafts used at our institution since 1/2001 and the corresponding 11 PIT recipients were studied. The CMV serology of all organ donors was tested using a latex agglutination assay for anti-CMV antibody (CMV Scan™, Becton Dickinson®, Cockeysville, MD), a test capable of detecting one CMV-infected cell per 50,000 cells. Following PIT, recipients were closely monitored for clinical symptoms consistent with CMV infection. All patients were tested monthly for the presence of CMV antigenemia using immunofluorescent monoclonal antibodies for the CMV pp65 antigen (Light Diagnostics™, Chemicon®, Temecula, CA). All patients received valganciclovir 450 mg PO BID for 3 months following each PIT. Immunosuppression consisted of daclizumab, sirolimus, and tacrolimus. Results. Eight of the PIT recipients (72%) were CMV seronegative prior to PIT (R−). Eighteen of the 26 Pancreatic Islet grafts (69%) were from CMV+ donors (D+), and the remaining eight (31%) were from CMV− donors (D−). A single R− recipient received only D− Pancreatic Islets, while the remaining seven received at least one D+ Pancreatic Islets graft. In all there were 6 D+R+, 3 D−R+, 12 D+R−, and 5 D−R− PITs. No patient developed symptoms consistent with CMV infection at any time following PIT. Monthly routine blood testing of all recipients has revealed no detectable CMV antigenemia in any patient. Conclusion. In our series neither CMV transmission nor CMV infection was seen after PIT. The risk of CMV transmission is lower after PIT than the risk after simultaneous kidney--pancreas transplantation.
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procurement of the human pancreas for Pancreatic Islet transplantation
Transplantation, 2004Co-Authors: Neal R Barshes, Charles F Brunicardi, Liz Nguyen, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background. The full potential of Pancreatic Islet transplantation (PIT) has not been realized because of the difficulties associated with Islet isolation, particularly when associated with a remote Islet isolation center. Herein, we describe the principles of Pancreatic procurement for PIT, which have allowed us to achieve a successful Pancreatic Islet isolation rate 67% of the time when using a remote Islet isolation center. Methods. Between January 16, 2002 and June 30, 2003, 39 pancreata were procured and processed for PIT at a distant Islet isolation center. All pancreata were procured by a single surgeon, and special attention was given to careful dissection of the pancreas, maintenance of arterial inflow and the pressure differential between arterial and venous systems during perfusion, rapid organ cooling, and rapid removal of the pancreas from the body. Results. Twenty-six of 39 (67%) procured pancreata yielded more tha 5,000 Islet equivalents (IEQ)/kg recipient weight and were transplanted. Median IEQs per isolation was 413,867, whereas median purity and viability were 65% and 100%, respectively. The median time for Pancreatic excision was 34 minutes, whereas cold ischemia time was 6 hours and 40 minutes. Discussion. The principles we have adopted for Pancreatic procurement for PIT have resulted in a 67% Islet isolation success rate despite the maintenance of more than 5,000 IEQ/kg and the use of a remote Islet isolation center.
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Development of a human Pancreatic Islet-transplant program through a collaborative relationship with a remote Islet-isolation center
Transplantation, 2004Co-Authors: John A. Goss, Sarah E. Goodpastor, Merle Barth, George D. Soltes, Dale J. Hamilton, Alan J. Garber, Rodolfo Alejandro, F. Charles Brunicardi, Camillo RicordiAbstract:Background. With the development of the Edmonton Protocol, Pancreatic Islet transplantation (PIT) now offers insulin-dependent diabetic patients metabolic stability. The PIT Food and Drug Administration (FDA) regulations, Pancreatic Islet isolation (PII) techniques, and clinical PIT protocols are challenging and make PIT program development daunting. Purpose. Review of the establishment of a PIT program through a collaborative relationship with a remote PIT/PII center. Methods. Four key elements are required: (1) development of a collaborative relationship with an established PIT/PII center, (2) achievement of institutional review board and FDA approval at both centers, (3) generation of standard operating procedures, and (4) development of a multidisciplinary PIT team. Results. Securing a collaborative relationship with an experienced PIT/PII center permitted our program to develop in less than 18 months. Twenty-two PITs were completed in the first clinical year. Conclusions. Collaboration with an experienced PIT/PII center allows developing programs to focus on patient safety and care, prudent use of pancreata, and consolidates PII expertise and experience.
Neal R Barshes - One of the best experts on this subject based on the ideXlab platform.
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inflammation mediated dysfunction and apoptosis in Pancreatic Islet transplantation implications for intrahepatic grafts
Journal of Leukocyte Biology, 2005Co-Authors: Neal R Barshes, Samuel Wyllie, John A. GossAbstract:Recent advances in clinical protocols have improved the outcomes of Pancreatic Islet transplantation (PIT), yet PIT recipients typically require Pancreatic Islet grafts derived from multi- ple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of Pancreatic Islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involve- ment of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1 appears to be among the most important inflammatory mediators, causing pan- creatic Islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) syn- thase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the Pancreatic Islets, and depletion or inhibition of Kupffer cells improves outcomes following exper- imental PIT. Immediately after transplantation, the Pancreatic Islets are perfused only by portal vein blood until the process of angiogenesis re- stores arterial blood flow some 7-10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion mole- cules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the imme- diate post-transplant period, hepatocytes may con- tribute to Pancreatic Islet injury through the pro- duction of NO. This paper reviews literature re- garding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the patho- physiology of hepatic ischemia-reperfusion and their relation to the survival and function of intra- hepatic Pancreatic Islet grafts. J. Leukoc. Biol. 77: 000-000; 2005.
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transaminitis after Pancreatic Islet transplantation
Journal of The American College of Surgeons, 2005Co-Authors: Neal R Barshes, Amy Mote, Paige A Schock, Sarah E. Goodpastor, Charles F Brunicardi, Rajesh Balkrishnan, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background An asymptomatic, self-limited transaminitis uniformly follows Pancreatic Islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote Pancreatic Islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the Pancreatic Islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.
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Lack of cytomegalovirus infection after Pancreatic Islet transplantation
Journal of Surgical Research, 2004Co-Authors: Neal R Barshes, Brian J. Williams, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Abstract Background. Cytomegalovirus (CMV) infection in the immunosuppressed transplant recipient is a cause of significant morbidity. With ganciclovir prophylaxis, the overall incidence of CMV after simultaneous kidney-whole pancreas transplantation remains as high as 40%, while CMV infection has never been reported following Pancreatic Islet transplantation (PIT) alone (i.e., without kidney transplantation). We designed the following study to objectively quantify the rate of transmission of CMV after clinical PIT. Methods. The 26 Pancreatic Islet grafts used at our institution since 1/2001 and the corresponding 11 PIT recipients were studied. The CMV serology of all organ donors was tested using a latex agglutination assay for anti-CMV antibody (CMV Scan™, Becton Dickinson®, Cockeysville, MD), a test capable of detecting one CMV-infected cell per 50,000 cells. Following PIT, recipients were closely monitored for clinical symptoms consistent with CMV infection. All patients were tested monthly for the presence of CMV antigenemia using immunofluorescent monoclonal antibodies for the CMV pp65 antigen (Light Diagnostics™, Chemicon®, Temecula, CA). All patients received valganciclovir 450 mg PO BID for 3 months following each PIT. Immunosuppression consisted of daclizumab, sirolimus, and tacrolimus. Results. Eight of the PIT recipients (72%) were CMV seronegative prior to PIT (R−). Eighteen of the 26 Pancreatic Islet grafts (69%) were from CMV+ donors (D+), and the remaining eight (31%) were from CMV− donors (D−). A single R− recipient received only D− Pancreatic Islets, while the remaining seven received at least one D+ Pancreatic Islets graft. In all there were 6 D+R+, 3 D−R+, 12 D+R−, and 5 D−R− PITs. No patient developed symptoms consistent with CMV infection at any time following PIT. Monthly routine blood testing of all recipients has revealed no detectable CMV antigenemia in any patient. Conclusion. In our series neither CMV transmission nor CMV infection was seen after PIT. The risk of CMV transmission is lower after PIT than the risk after simultaneous kidney--pancreas transplantation.
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procurement of the human pancreas for Pancreatic Islet transplantation
Transplantation, 2004Co-Authors: Neal R Barshes, Charles F Brunicardi, Liz Nguyen, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background. The full potential of Pancreatic Islet transplantation (PIT) has not been realized because of the difficulties associated with Islet isolation, particularly when associated with a remote Islet isolation center. Herein, we describe the principles of Pancreatic procurement for PIT, which have allowed us to achieve a successful Pancreatic Islet isolation rate 67% of the time when using a remote Islet isolation center. Methods. Between January 16, 2002 and June 30, 2003, 39 pancreata were procured and processed for PIT at a distant Islet isolation center. All pancreata were procured by a single surgeon, and special attention was given to careful dissection of the pancreas, maintenance of arterial inflow and the pressure differential between arterial and venous systems during perfusion, rapid organ cooling, and rapid removal of the pancreas from the body. Results. Twenty-six of 39 (67%) procured pancreata yielded more tha 5,000 Islet equivalents (IEQ)/kg recipient weight and were transplanted. Median IEQs per isolation was 413,867, whereas median purity and viability were 65% and 100%, respectively. The median time for Pancreatic excision was 34 minutes, whereas cold ischemia time was 6 hours and 40 minutes. Discussion. The principles we have adopted for Pancreatic procurement for PIT have resulted in a 67% Islet isolation success rate despite the maintenance of more than 5,000 IEQ/kg and the use of a remote Islet isolation center.
Rodolfo Alejandro - One of the best experts on this subject based on the ideXlab platform.
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transaminitis after Pancreatic Islet transplantation
Journal of The American College of Surgeons, 2005Co-Authors: Neal R Barshes, Amy Mote, Paige A Schock, Sarah E. Goodpastor, Charles F Brunicardi, Rajesh Balkrishnan, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background An asymptomatic, self-limited transaminitis uniformly follows Pancreatic Islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote Pancreatic Islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the Pancreatic Islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.
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Lack of cytomegalovirus infection after Pancreatic Islet transplantation
Journal of Surgical Research, 2004Co-Authors: Neal R Barshes, Brian J. Williams, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Abstract Background. Cytomegalovirus (CMV) infection in the immunosuppressed transplant recipient is a cause of significant morbidity. With ganciclovir prophylaxis, the overall incidence of CMV after simultaneous kidney-whole pancreas transplantation remains as high as 40%, while CMV infection has never been reported following Pancreatic Islet transplantation (PIT) alone (i.e., without kidney transplantation). We designed the following study to objectively quantify the rate of transmission of CMV after clinical PIT. Methods. The 26 Pancreatic Islet grafts used at our institution since 1/2001 and the corresponding 11 PIT recipients were studied. The CMV serology of all organ donors was tested using a latex agglutination assay for anti-CMV antibody (CMV Scan™, Becton Dickinson®, Cockeysville, MD), a test capable of detecting one CMV-infected cell per 50,000 cells. Following PIT, recipients were closely monitored for clinical symptoms consistent with CMV infection. All patients were tested monthly for the presence of CMV antigenemia using immunofluorescent monoclonal antibodies for the CMV pp65 antigen (Light Diagnostics™, Chemicon®, Temecula, CA). All patients received valganciclovir 450 mg PO BID for 3 months following each PIT. Immunosuppression consisted of daclizumab, sirolimus, and tacrolimus. Results. Eight of the PIT recipients (72%) were CMV seronegative prior to PIT (R−). Eighteen of the 26 Pancreatic Islet grafts (69%) were from CMV+ donors (D+), and the remaining eight (31%) were from CMV− donors (D−). A single R− recipient received only D− Pancreatic Islets, while the remaining seven received at least one D+ Pancreatic Islets graft. In all there were 6 D+R+, 3 D−R+, 12 D+R−, and 5 D−R− PITs. No patient developed symptoms consistent with CMV infection at any time following PIT. Monthly routine blood testing of all recipients has revealed no detectable CMV antigenemia in any patient. Conclusion. In our series neither CMV transmission nor CMV infection was seen after PIT. The risk of CMV transmission is lower after PIT than the risk after simultaneous kidney--pancreas transplantation.
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procurement of the human pancreas for Pancreatic Islet transplantation
Transplantation, 2004Co-Authors: Neal R Barshes, Charles F Brunicardi, Liz Nguyen, Rodolfo Alejandro, Camillo Ricordi, John A. GossAbstract:Background. The full potential of Pancreatic Islet transplantation (PIT) has not been realized because of the difficulties associated with Islet isolation, particularly when associated with a remote Islet isolation center. Herein, we describe the principles of Pancreatic procurement for PIT, which have allowed us to achieve a successful Pancreatic Islet isolation rate 67% of the time when using a remote Islet isolation center. Methods. Between January 16, 2002 and June 30, 2003, 39 pancreata were procured and processed for PIT at a distant Islet isolation center. All pancreata were procured by a single surgeon, and special attention was given to careful dissection of the pancreas, maintenance of arterial inflow and the pressure differential between arterial and venous systems during perfusion, rapid organ cooling, and rapid removal of the pancreas from the body. Results. Twenty-six of 39 (67%) procured pancreata yielded more tha 5,000 Islet equivalents (IEQ)/kg recipient weight and were transplanted. Median IEQs per isolation was 413,867, whereas median purity and viability were 65% and 100%, respectively. The median time for Pancreatic excision was 34 minutes, whereas cold ischemia time was 6 hours and 40 minutes. Discussion. The principles we have adopted for Pancreatic procurement for PIT have resulted in a 67% Islet isolation success rate despite the maintenance of more than 5,000 IEQ/kg and the use of a remote Islet isolation center.
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Development of a human Pancreatic Islet-transplant program through a collaborative relationship with a remote Islet-isolation center
Transplantation, 2004Co-Authors: John A. Goss, Sarah E. Goodpastor, Merle Barth, George D. Soltes, Dale J. Hamilton, Alan J. Garber, Rodolfo Alejandro, F. Charles Brunicardi, Camillo RicordiAbstract:Background. With the development of the Edmonton Protocol, Pancreatic Islet transplantation (PIT) now offers insulin-dependent diabetic patients metabolic stability. The PIT Food and Drug Administration (FDA) regulations, Pancreatic Islet isolation (PII) techniques, and clinical PIT protocols are challenging and make PIT program development daunting. Purpose. Review of the establishment of a PIT program through a collaborative relationship with a remote PIT/PII center. Methods. Four key elements are required: (1) development of a collaborative relationship with an established PIT/PII center, (2) achievement of institutional review board and FDA approval at both centers, (3) generation of standard operating procedures, and (4) development of a multidisciplinary PIT team. Results. Securing a collaborative relationship with an experienced PIT/PII center permitted our program to develop in less than 18 months. Twenty-two PITs were completed in the first clinical year. Conclusions. Collaboration with an experienced PIT/PII center allows developing programs to focus on patient safety and care, prudent use of pancreata, and consolidates PII expertise and experience.
Kazutomo Inoue - One of the best experts on this subject based on the ideXlab platform.
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successful subcutaneous Pancreatic Islet transplantation using an angiogenic growth factor releasing device
Pancreas, 2001Co-Authors: Yoshiyuki Kawakami, Yuan J Gu, Appakalai N. Balamurugan, Yoshinobu Murakami, Masayuki Imamura, Hiroo Iwata, Masaaki Miyamoto, Kazutomo InoueAbstract:Introduction: Although the subcutaneous tissue is considered as an attractive site for Pancreatic Islet transplantation, the success rate has been extremely low. Aims: To use basic fibroblast growth factor (bFGF) to induce neovascularization and sufficient blood flow around the space formed for grafted Islets in the subcutaneous tissue to improve the Islet survival. Methodology: In the experimental group, two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue (back) of diabetic Lewis rats. One week after implantation, in the same site, isolated rat Islets were syngeneically transplanted after the removal of the devices. In the control group, two devices without bFGF were implanted before subcutaneous Islet transplantation of the same number of Islets. Results: One week after the implantation of the bFGF-releasing devices in the experimental animals, the devices induced angiogenesis by slow release of bFGF. After transplantation of Islets, the neovascularized recipient rats showed significant decreases in nonfasting blood glucose concentration and maintained normoglycemia for more than 3 months. However, in the control group, all rats failed to achieve normoglycemia after transplantation in the absence of neovascularization. Conclusion: This study provides evidence that the subcutaneous tissue is a promising site for Pancreatic Islet transplantation, which suggests the acceptability of this treatment for diabetic recipients.
