Robert Harland - Academia.edu (original) (raw)
Papers by Robert Harland
Transplant international : official journal of the European Society for Organ Transplantation, Jan 14, 2017
Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports de... more Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies had polyoma virus large T-antigen expression in tubular epithelium by immunohistochemistry. All had viuria preceding or at the time of biopsy (range, 5.2x10(4) to > 25x10(6) BKV DNA copies/mL). Twenty (69%) had viremia ranging from 2.5x10(3) to 4.3x10(6) copies/mL at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed ...
Surgery, 2016
Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantati... more Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantation. Use of extended criteria donors (ECD) may help with donor allocation in these patients. The objective of this study was to determine the use of ECDs in patients with nonalcoholic steatohepatitis undergoing liver transplantation to stimulate a liver-specific predictive model for ECD use. The United Network for Organ Sharing database was used to identify patients undergoing liver transplantation for nonalcoholic steatohepatitis (2002-2014). Cox hazards models were created using (1) United Network for Organ Sharing ECD criteria (based on kidney allocation), (2) individual donor characteristics (age, sex, race, cause of death, body mass index, cold ischemic time), and (3) the Kidney Donor Profile Index (KDPI) to examine the effect of ECDs on mortality and graft failure. A total of 4,387 patients underwent liver transplantation for nonalcoholic steatohepatitis; 1,359 (30.9%) patients received an ECD. Transplantation with ECD livers had comparable patient survival (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.91-1.23) between donor types but an increased risk of graft failure (HR 1.18, 95% CI 1.03-1.36) compared to standard donors. Individual characteristics did not affect patient survival or graft failure. A 10% increase in KDPI was associated with a 28% increase in patient mortality (HR 1.28, 95% CI 1.02-1.60) and 45% increase in graft failure (HR 1.45, 95% CI 1.18-1.80). Based on the current United Network for Organ Sharing definition, ECDs in nonalcoholic steatohepatitis were associated with similar overall survival but increased risk of graft failure. Given the shortage of organs, creation of an easily calculated, liver-specific model similar to the KDPI may help risk stratify patients and improve organ allocation.
Transplantation, 1999
In recent years, hepatic support systems using xenogeneic cells have been developed to support pa... more In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM,1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3alpha-hydroxy-6-oxo-5beta-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. The mean duration of perfusions was 4.1+/-1.5 hr. The mean total bile acid clearance from serum (243+/-44 micromol/h) was similar to the total bile acid biliary excretion (286+/-84 micromol/hr, P = 0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.
Transplantation Proceedings, Sep 1, 1998
C YTOMEGALOVIRUS (CMV) remains an important contributor to morbidity in renal transplant recipien... more C YTOMEGALOVIRUS (CMV) remains an important contributor to morbidity in renal transplant recipients and may also be associated with both acute rejection 1 and chronic allograft failure. 2 Available pharmacologic approaches to prevent CMV disease are expensive and not universally effective. It remains unclear which regimen for CMV prophylaxis is most effective and which patients should receive it. Our center has had a relatively low rate of tissue-invasive CMV disease, perhaps because antilymphocyte therapy for induction immunosuppression is not used except for patients receiving a simultaneous kidney and pancreas transplant. To guide the use of CMV prophylaxis, we sought to quantify the incidence of CMV infection and its effect on graft survival in our renal transplant recipients.
Clinical Transplants, 2013
Donor specific human leukocyte antigen (HLA) antibodies (DSA) are a significant cause of allograf... more Donor specific human leukocyte antigen (HLA) antibodies (DSA) are a significant cause of allograft failure. However, it has been reported that some DSA negative patients still experience allograft failure. In addition, some DSA positive patients maintain good graft function for >20 years. These findings suggest that while DSA is a cause of failure, it is not the sole risk factor for graft dysfunction and that the presence of DSA alone may not predict the time course of graft failure. Here, we report the predictive value of a proprietary panel of four biomarkers in long-term renal allograft outcome. A total of 310 consecutive patients, who received kidney transplants between 1999 and 2012, were included in this study. Recipient sera was tested for HLA antibodies and biomarkers at 3, 6, 12, 24, and 36 months post-transplant. HLA antibodies were identified using Labscreen single antigen beads. The biomarker combination (BMC) test consisted of a proprietary panel of 4 biomarkers and was performed using Luminex. Sera were defined as positive when any one of the 4 biomarkers became detectable. Sera of normal healthy people were used as negative controls. Graft survival analyses were performed and compared between different patient groups based on the positivity of DSA and BMC. Our results indicate that 57% of DSA negative patients and 54% of DSA positive patients had detectable biomarkers. There was no significant difference in BMC positive patients between the DSA positive and negative groups, which suggests that presence of BMC is not associated with HLA DSA. DSA positive patients had a 10% lower 10-year graft survival rate than patients without DSA, while BMC positive patients had a 25% lower 10-year graft survival rate than patients without detectable BMC. When DSA negative patients were divided into two groups based on the positivity of BMC, BMC positive patients had a 20% lower 10-year graft survival rate compared to BMC negative patients…
Journal of the American College of Surgeons, Jul 1, 2006
Transplantation of cadaveric pancreas has evolved as an effective and established treatment for p... more Transplantation of cadaveric pancreas has evolved as an effective and established treatment for patients with type 1 diabetes mellitus. A recent analysis of more than 23,000 pancreas transplants reported as of December 2004 revealed a growing tendency to enterically drain the pancreas 1 ; reported drainage methods connect the graft duodenum with a Roux-en-Y limb, or use end-toside or side-to-side anastomosis. 2-5 Enteric drainage, although increasingly popular, is associated with a number of early surgical complications, including mechanical intestinal obstruction, duodenal anastomotic leak, and intraabdominal sepsis. 4 Their reported incidence, depending on the complications' severity, ranges from 35% to 80%, 6 and they necessitate relaparotomy in up to 43% of patients. In an attempt to decrease the risk of complications, we have developed a novel enteric drainage method and report the preliminary results with our first consecutive patients in whom it was used.
N Engl J Med, 1994
In 1990, more than 27,000 patients died of liver failure in the United States 1 . Perfusion throu... more In 1990, more than 27,000 patients died of liver failure in the United States 1 . Perfusion through a liver from another person or a member of another species, such as a monkey, outside the body was used in the past to stabilize the condition of some patients with acute or subacute ...
Transplantation, May 1, 2006
... Julian E. Losanoff. Robert C. Harland. James E. Williams. Oswaldo E. Rivero. Trevor W. Reichm... more ... Julian E. Losanoff. Robert C. Harland. James E. Williams. Oswaldo E. Rivero. Trevor W. Reichman. J. Michael Millis. Section of Transplantation. ... RB, Giatras I, Falagas ME. Outcome of transplantation of organs procured from bacteremic donors. Transplantation 1999; 68: 1107-1111 ...
The American Journal of Physiology, 1999
Transplantation, Nov 1, 1995
A major question in xenotransplantation is the nature of the humoral response that would occur fo... more A major question in xenotransplantation is the nature of the humoral response that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could mediate delayed types of injury to the graft. To begin to address this issue we characterized the changes in the properties of xenoreactive antibodies occurring in patients exposed to porcine organs under conditions simulating transplantation. In two patients whose blood had been cross-perfused through porcine livers as a treatment for hepatic failure, the titer of xenoreactive IgM increased by four-fold and the titer of xenoreactive IgG increased by sixty-fold within ten days after perfusion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells and bovine thyroglobulin, which express this determinant, and on the decrease in binding following treatment of porcine endothelial cells or bovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-binding sites obtained before and ten days after perfusion of porcine organs revealed no increase in binding of IgM above the level observed with serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to porcine endothelial cells of IgM in serum obtained before and ten days after perfusion of porcine organs was unchanged. Even at later times, the presence of newly elicited antibodies against porcine aortic endothelial cell targets was not detected. Thus, exposure to porcine antigens in a vascularized organ results in increases in the levels of xenoreactive IgM and IgG antibodies--however, these antibodies exhibit properties similar to natural antibodies.
The American journal of physiology, 1998
Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. ... more Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin -/-, ICAM-1 -/-, and L-selectin/ICAM-1 -/-) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-defici...
Cell transplantation
Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. How... more Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. However, the process of isolating, purifying, encapsulating, and transplanting islets in a single day is labor intensive and difficult for routine use. There is an apparent need for reliable methods of islet storage, and cryopreservation has emerged as an attractive system of islet banking. While studies have shown that cryopreserved islets are viable when tested unencapsulated after thawing, it is not clear if the combination of freezing and encapsulation would affect islet function. The purpose of the present study was to determine the in vitro function of cryopreserved islets following thawing and microencapsulation. Islets were isolated from the pancreata of Sprague-Dawley rats and cryopreserved under liquid nitrogen for either 1 week or 1 month, following an overnight culture at 37 degrees C. Upon thawing, the islets were tested either unencapsulated or after encapsulation in polylysin...
Clinical transplants, 1996
1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United St... more 1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United States. 2. SEOPF centers transplanted better-matched kidneys than the rest of the nation despite transplanting a significantly larger percentage of "hard-to-match" black recipients. 3. Within SEOPF centers, a shared kidney was almost twice as likely to be a good match (zero-3 HLA antigen mismatches) as was a local kidney. 4. Within SEOPF centers, well-matched kidneys (zero-3 HLA antigen mismatches) had significantly better graft survival than did poorly-matched (4-6 HLA antigen mismatches) kidneys. 5. SEOPF centers had one-, 2- and 3-year graft survival rates comparable to those of the rest of the nation. 6. SEOPF centers have proven the efficiency of ROP trays in predicting final crossmatch results for shared kidneys. 7. The SEOPF High Grade Match (HGM) algorithm has been successful in transplanting highly sensitized (current PRA > 40%) recipients. 8. The use of ROP trays in ...
Clinical transplantation, 1996
Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since urs... more Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since ursodeoxycholic acid (UDCA) is beneficial in several cholestatic disorders and possesses in vitro immunomodulatory and immunosuppressive effects, we have tested in a pilot study the effects of adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive liver transplant patients were treated with a standard cyclosporine immunosuppressive regimen. Treatment with UDCA (10 mg/kg/d) was initiated in each patient who developed biopsy-proven rejection or biochemical evidence of cholestasis. Clinical and laboratory features were monitored for evidence of rejection. Data were analyzed after at least a 10-month follow-up period was available in each patient. Seven patients died during the study period, all within 4 wk of surgery. No evidence of rejection was documented in these patients. Twenty three of the 43 survivors 53% (23/43) developed an episode of rejection, and UDCA was...
Transplantation proceedings, 1996
Transplantation proceedings, 1994
Transplantation proceedings, 1995
Transplantation proceedings, 1994
Transplant international : official journal of the European Society for Organ Transplantation, Jan 14, 2017
Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports de... more Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies had polyoma virus large T-antigen expression in tubular epithelium by immunohistochemistry. All had viuria preceding or at the time of biopsy (range, 5.2x10(4) to > 25x10(6) BKV DNA copies/mL). Twenty (69%) had viremia ranging from 2.5x10(3) to 4.3x10(6) copies/mL at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed ...
Surgery, 2016
Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantati... more Nonalcoholic steatohepatitis is expected to become the leading indication for liver transplantation. Use of extended criteria donors (ECD) may help with donor allocation in these patients. The objective of this study was to determine the use of ECDs in patients with nonalcoholic steatohepatitis undergoing liver transplantation to stimulate a liver-specific predictive model for ECD use. The United Network for Organ Sharing database was used to identify patients undergoing liver transplantation for nonalcoholic steatohepatitis (2002-2014). Cox hazards models were created using (1) United Network for Organ Sharing ECD criteria (based on kidney allocation), (2) individual donor characteristics (age, sex, race, cause of death, body mass index, cold ischemic time), and (3) the Kidney Donor Profile Index (KDPI) to examine the effect of ECDs on mortality and graft failure. A total of 4,387 patients underwent liver transplantation for nonalcoholic steatohepatitis; 1,359 (30.9%) patients received an ECD. Transplantation with ECD livers had comparable patient survival (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.91-1.23) between donor types but an increased risk of graft failure (HR 1.18, 95% CI 1.03-1.36) compared to standard donors. Individual characteristics did not affect patient survival or graft failure. A 10% increase in KDPI was associated with a 28% increase in patient mortality (HR 1.28, 95% CI 1.02-1.60) and 45% increase in graft failure (HR 1.45, 95% CI 1.18-1.80). Based on the current United Network for Organ Sharing definition, ECDs in nonalcoholic steatohepatitis were associated with similar overall survival but increased risk of graft failure. Given the shortage of organs, creation of an easily calculated, liver-specific model similar to the KDPI may help risk stratify patients and improve organ allocation.
Transplantation, 1999
In recent years, hepatic support systems using xenogeneic cells have been developed to support pa... more In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM,1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3alpha-hydroxy-6-oxo-5beta-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. The mean duration of perfusions was 4.1+/-1.5 hr. The mean total bile acid clearance from serum (243+/-44 micromol/h) was similar to the total bile acid biliary excretion (286+/-84 micromol/hr, P = 0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.
Transplantation Proceedings, Sep 1, 1998
C YTOMEGALOVIRUS (CMV) remains an important contributor to morbidity in renal transplant recipien... more C YTOMEGALOVIRUS (CMV) remains an important contributor to morbidity in renal transplant recipients and may also be associated with both acute rejection 1 and chronic allograft failure. 2 Available pharmacologic approaches to prevent CMV disease are expensive and not universally effective. It remains unclear which regimen for CMV prophylaxis is most effective and which patients should receive it. Our center has had a relatively low rate of tissue-invasive CMV disease, perhaps because antilymphocyte therapy for induction immunosuppression is not used except for patients receiving a simultaneous kidney and pancreas transplant. To guide the use of CMV prophylaxis, we sought to quantify the incidence of CMV infection and its effect on graft survival in our renal transplant recipients.
Clinical Transplants, 2013
Donor specific human leukocyte antigen (HLA) antibodies (DSA) are a significant cause of allograf... more Donor specific human leukocyte antigen (HLA) antibodies (DSA) are a significant cause of allograft failure. However, it has been reported that some DSA negative patients still experience allograft failure. In addition, some DSA positive patients maintain good graft function for >20 years. These findings suggest that while DSA is a cause of failure, it is not the sole risk factor for graft dysfunction and that the presence of DSA alone may not predict the time course of graft failure. Here, we report the predictive value of a proprietary panel of four biomarkers in long-term renal allograft outcome. A total of 310 consecutive patients, who received kidney transplants between 1999 and 2012, were included in this study. Recipient sera was tested for HLA antibodies and biomarkers at 3, 6, 12, 24, and 36 months post-transplant. HLA antibodies were identified using Labscreen single antigen beads. The biomarker combination (BMC) test consisted of a proprietary panel of 4 biomarkers and was performed using Luminex. Sera were defined as positive when any one of the 4 biomarkers became detectable. Sera of normal healthy people were used as negative controls. Graft survival analyses were performed and compared between different patient groups based on the positivity of DSA and BMC. Our results indicate that 57% of DSA negative patients and 54% of DSA positive patients had detectable biomarkers. There was no significant difference in BMC positive patients between the DSA positive and negative groups, which suggests that presence of BMC is not associated with HLA DSA. DSA positive patients had a 10% lower 10-year graft survival rate than patients without DSA, while BMC positive patients had a 25% lower 10-year graft survival rate than patients without detectable BMC. When DSA negative patients were divided into two groups based on the positivity of BMC, BMC positive patients had a 20% lower 10-year graft survival rate compared to BMC negative patients…
Journal of the American College of Surgeons, Jul 1, 2006
Transplantation of cadaveric pancreas has evolved as an effective and established treatment for p... more Transplantation of cadaveric pancreas has evolved as an effective and established treatment for patients with type 1 diabetes mellitus. A recent analysis of more than 23,000 pancreas transplants reported as of December 2004 revealed a growing tendency to enterically drain the pancreas 1 ; reported drainage methods connect the graft duodenum with a Roux-en-Y limb, or use end-toside or side-to-side anastomosis. 2-5 Enteric drainage, although increasingly popular, is associated with a number of early surgical complications, including mechanical intestinal obstruction, duodenal anastomotic leak, and intraabdominal sepsis. 4 Their reported incidence, depending on the complications' severity, ranges from 35% to 80%, 6 and they necessitate relaparotomy in up to 43% of patients. In an attempt to decrease the risk of complications, we have developed a novel enteric drainage method and report the preliminary results with our first consecutive patients in whom it was used.
N Engl J Med, 1994
In 1990, more than 27,000 patients died of liver failure in the United States 1 . Perfusion throu... more In 1990, more than 27,000 patients died of liver failure in the United States 1 . Perfusion through a liver from another person or a member of another species, such as a monkey, outside the body was used in the past to stabilize the condition of some patients with acute or subacute ...
Transplantation, May 1, 2006
... Julian E. Losanoff. Robert C. Harland. James E. Williams. Oswaldo E. Rivero. Trevor W. Reichm... more ... Julian E. Losanoff. Robert C. Harland. James E. Williams. Oswaldo E. Rivero. Trevor W. Reichman. J. Michael Millis. Section of Transplantation. ... RB, Giatras I, Falagas ME. Outcome of transplantation of organs procured from bacteremic donors. Transplantation 1999; 68: 1107-1111 ...
The American Journal of Physiology, 1999
Transplantation, Nov 1, 1995
A major question in xenotransplantation is the nature of the humoral response that would occur fo... more A major question in xenotransplantation is the nature of the humoral response that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could mediate delayed types of injury to the graft. To begin to address this issue we characterized the changes in the properties of xenoreactive antibodies occurring in patients exposed to porcine organs under conditions simulating transplantation. In two patients whose blood had been cross-perfused through porcine livers as a treatment for hepatic failure, the titer of xenoreactive IgM increased by four-fold and the titer of xenoreactive IgG increased by sixty-fold within ten days after perfusion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells and bovine thyroglobulin, which express this determinant, and on the decrease in binding following treatment of porcine endothelial cells or bovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-binding sites obtained before and ten days after perfusion of porcine organs revealed no increase in binding of IgM above the level observed with serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to porcine endothelial cells of IgM in serum obtained before and ten days after perfusion of porcine organs was unchanged. Even at later times, the presence of newly elicited antibodies against porcine aortic endothelial cell targets was not detected. Thus, exposure to porcine antigens in a vascularized organ results in increases in the levels of xenoreactive IgM and IgG antibodies--however, these antibodies exhibit properties similar to natural antibodies.
The American journal of physiology, 1998
Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. ... more Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin -/-, ICAM-1 -/-, and L-selectin/ICAM-1 -/-) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-defici...
Cell transplantation
Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. How... more Microencapsulation is an effective means of immunoisolation for pancreatic islet transplants. However, the process of isolating, purifying, encapsulating, and transplanting islets in a single day is labor intensive and difficult for routine use. There is an apparent need for reliable methods of islet storage, and cryopreservation has emerged as an attractive system of islet banking. While studies have shown that cryopreserved islets are viable when tested unencapsulated after thawing, it is not clear if the combination of freezing and encapsulation would affect islet function. The purpose of the present study was to determine the in vitro function of cryopreserved islets following thawing and microencapsulation. Islets were isolated from the pancreata of Sprague-Dawley rats and cryopreserved under liquid nitrogen for either 1 week or 1 month, following an overnight culture at 37 degrees C. Upon thawing, the islets were tested either unencapsulated or after encapsulation in polylysin...
Clinical transplants, 1996
1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United St... more 1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United States. 2. SEOPF centers transplanted better-matched kidneys than the rest of the nation despite transplanting a significantly larger percentage of "hard-to-match" black recipients. 3. Within SEOPF centers, a shared kidney was almost twice as likely to be a good match (zero-3 HLA antigen mismatches) as was a local kidney. 4. Within SEOPF centers, well-matched kidneys (zero-3 HLA antigen mismatches) had significantly better graft survival than did poorly-matched (4-6 HLA antigen mismatches) kidneys. 5. SEOPF centers had one-, 2- and 3-year graft survival rates comparable to those of the rest of the nation. 6. SEOPF centers have proven the efficiency of ROP trays in predicting final crossmatch results for shared kidneys. 7. The SEOPF High Grade Match (HGM) algorithm has been successful in transplanting highly sensitized (current PRA > 40%) recipients. 8. The use of ROP trays in ...
Clinical transplantation, 1996
Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since urs... more Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since ursodeoxycholic acid (UDCA) is beneficial in several cholestatic disorders and possesses in vitro immunomodulatory and immunosuppressive effects, we have tested in a pilot study the effects of adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive liver transplant patients were treated with a standard cyclosporine immunosuppressive regimen. Treatment with UDCA (10 mg/kg/d) was initiated in each patient who developed biopsy-proven rejection or biochemical evidence of cholestasis. Clinical and laboratory features were monitored for evidence of rejection. Data were analyzed after at least a 10-month follow-up period was available in each patient. Seven patients died during the study period, all within 4 wk of surgery. No evidence of rejection was documented in these patients. Twenty three of the 43 survivors 53% (23/43) developed an episode of rejection, and UDCA was...
Transplantation proceedings, 1996
Transplantation proceedings, 1994
Transplantation proceedings, 1995
Transplantation proceedings, 1994