Home About us Contact
|
Home About us Contact | ||
|
|
||
Posttransplantation
Kinds of Posttransplantation Terms modified by Posttransplantation Selected AbstractsTransplanted astrocytes internalize deposited ,-amyloid peptides in a transgenic mouse model of Alzheimer's diseaseGLIA, Issue 2 2008Rea Pihlaja Abstract Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. The neuropathological hallmarks include extracellular senile plaques consisting of deposited ,-amyloid (A,) peptides and intraneuronal neurofibrillary tangles. Neuroinflammation and activation of astrocytes are also well-established features of AD neuropathology; however, the relationships between astrocytes and A, deposition remain unclear. Previous studies have shown that adult mouse astrocytes internalize and degrade A, deposits in brain sections prepared from human amyloid precursor protein (APP) transgenic mice. In the present study, we demonstrate that cultured adult, but not neonatal mouse astrocytes, respond morphologically and degrade A, deposits present in human AD brain. We also transplanted astrocytes isolated from enhanced green fluorescent protein expressing adult and neonatal mice into the hippocampi of human A, plaque-bearing transgenic APPSwe+PS1dE9 (APdE9) mice and their wild-type littermates and followed the migration and localization of these astrocytes by confocal microscopy upto 7 days after transplantation. Posttransplantation the astrocytes localized as aggregates or thin strings of many cells within the hippocampi of APdE9 and wild-type mice and showed limited migration from the injection site. Interestingly, most of the transplanted astrocytes were found near A, deposits in the hippocampi of APdE9 mice. In contrast to findings in ex vivo degradation assay, confocal microscopy revealed that both adult and neonatal transplanted astrocytes internalized human A, immunoreactive material in vivo. These results support the role of astrocytes as active A, clearing cells in the CNS that may have important implications for future development of therapeutic strategies for AD. © 2007 Wiley-Liss, Inc. [source] Prophylaxis Against Hepatitis B Recurrence Posttransplantation Using Lamivudine and Individualized Low-Dose Hepatitis B ImmunoglobulinAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010L. Jiang Although the combination of lamivudine (LAM) and high-dose intravenous (IV) hepatitis B immunoglobulin (HBIG) is very effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation (LT), the major limitation of this regimen is its high cost. A more cost-effective, convenient and widely accepted regimen is urgently needed. We evaluated the safety and efficacy of another strategy using LAM and individualized low-dose intramuscular (IM) HBIG. Between May 2002 and December 2009, a total of 254 adult patients undergoing LT for HBV-related benign end-stage liver diseases received this regimen in our center. The mean follow-up of these patients was 41.2 ± 22.7 months. Their 1-, 3- and 5-year survival rates were 85.3%, 77.4% and 76.4%, respectively, and 1-, 3- and 5-year HBV recurrence rates were 2.3%, 6.2% and 8.2%. Fourteen patients experienced posttransplant HBV recurrence. Pretransplant high viral load and posttransplant prednisone withdrawal time were observed to be associated with recurrence. In conclusion, combination therapy with LAM and individualized low-dose IM HBIG provides a safe and effective prophylaxis against HBV recurrence after LT at about 5% of the cost of conventional high-dose IV HBIG regimens. [source] Kidney Transplantation from Hepatitis B Surface Antigen Positive Donors into Hepatitis B Surface Antibody Positive Recipients: A Prospective Nonrandomized Controlled Study from a Single CenterAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009H. Jiang The number of patients on renal transplant waiting list is increasing rapidly in many countries, exacerbating the shortage of organs. We conducted a study to evaluate the safety and efficacy of deceased-donor kidney transplantation from hepatitis B surface antigen (HBsAg)-positive (+) donors into hepatitis B surface antibody (anti-HBs)-positive (+) recipients. Sixty-five patients received grafts from HBsAg(+) donors, and 308 subjects received grafts from HBsAg-negative(,) donors. Posttransplantation, recipients with HBsAg(,) grafts or HBsAg(+) grafts received 400 U of hepatitis B immunoglobulin once and twice, respectively. The seven recipients who received grafts from hepatitis B virus (HBV) DNA(+) donors were treated with hepatitis B immunoglobulin 400 U weekly for 3 months and lamivudine 100 mg daily for 6 months. All patients were monitored for liver function and hepatitis B viral status. The follow-up period was 38.7 ± 15.4 months. Although two recipients developed de novo HBV infection, neither patient developed severe liver dysfunction nor died. The incidence of liver injury (39/65 vs. 207/308, chi-square test, p > 0.05) and survival (log-rank test, p > 0.05) did not differ between the groups. We conclude that anti-HBs(+) recipients receiving HBsAg(+) grafts did as well as those receiving HBsAg(,) grafts. [source] Impact of Tips Preliver Transplantation for the Outcome PosttransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009G. P. Guerrini The effects of transjugular intrahepatic portocaval shunt (TIPS) on the survival of grafts and patients after liver transplantation (LTx) have only been documented in small series and with only a comparative description with non-TIPS recipients. We evaluated 61 TIPS patients who had a subsequent LTx and compared these with 591 patients transplanted with cirrhosis without TIPS. Pretransplant characteristics were similar between groups. Graft survival at 1, 3 and 5 years post-LTx was 85.2%, 77% and 72.1% (TIPS) and 75.3%, 69.8% and 66.1% (controls). Patient survival at the same points was 91.7%, 85% and 81.7%, respectively (TIPS) and 85.4%, 80.3% and 76.2% (controls). Cox regression showed the absence of TIPS pre-LTx, transfusion of >5 units of blood during LTx, intensive care unit (ICU) stay post-LTx >3 days and earlier period of transplant to be significantly associated with a worse patient and graft survival at 1 year. Migration of the TIPS stent occurred in 28% of cases, increasing the time on bypass during LTx, but was not related to graft or patient survival. TIPS may improve portal supply to the graft and reduce collateral flow, improving function. This may account for the improved adjusted graft and patient survival by Cox regression at 12 months. Long-term survival was not affected. [source] In Vivo Perfusion of Human Skin Substitutes With Microvessels Formed by Adult Circulating Endothelial Progenitor CellsDERMATOLOGIC SURGERY, Issue 2 2008ELAINE F. KUNG MD BACKGROUND At present, tissue-engineered human skin substitutes (HSSs) mainly function as temporary bioactive dressings due to inadequate perfusion. Failure to form functional vascular networks within the initial posttransplantation period compromises cell survival of the graft and its long-term viability in the wound bed. OBJECTIVES Our goal was to demonstrate that adult circulating endothelial progenitor cells (EPCs) seeded onto HSS can form functional microvessels capable of graft neovascularization and perfusion. MATERIALS AND METHODS Adult peripheral blood mononuclear cells (PBMCs) underwent CD34 selection and endothelial cell (EC) culture conditions. After in vitro expansion, flow cytometry verified EC phenotype before their incorporation into HSS. After 2 weeks in vivo, immunohistochemical analysis, immunofluorescent microscopy, and microfil polymer perfusion were performed. RESULTS CD34+ PBMCs differentiated into EPC demonstrating characteristic EC morphology and expression of CD31, Tie-2, and E-selectin after TNF,-induction. Numerous human CD31 and Ulex europaeus agglutinin-1 (UEA-1) microvessels within the engineered grafts (HSS/EPCs) inosculated with recipient murine circulation. Limitation of murine CD31 immunoreactivity to HSS margins showed angiogenesis was attributable to human EPC at 2 weeks posttransplantation. Delivery of intravenous rhodamine-conjugated UEA-1 and microfil polymer to HSS/EPCs demonstrated enhanced perfusion by functional microvessels compared to HSS control without EPCs. CONCLUSION We successfully engineered functional microvessels in HSS by incorporating adult circulating EPCs. This autologous EC source can form vascular conduits enabling perfusion and survival of human bioengineered tissues. [source] A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post,liver transplantation hepatitis B prophylaxis,HEPATOLOGY, Issue 5 2008Peter W. Angus Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen,positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 ,mol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine. Conclusion: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost. (HEPATOLOGY 2008.) [source] A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis CHEPATOLOGY, Issue 5 2002A. Obaid Shakil Although interferon alfa (IFN-,) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-, 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-, and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal. [source] Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantationHEPATOLOGY, Issue 5 2000Raghavakaimal Sreekumar Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre- and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (,109 copies/mL, n = 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r = .56, P , .001) and 3 years (r = .53, P = .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. Higher pre- and early post-LT HCV-RNA levels are associated with more severe recurrence of HCV. The correlation of early HAI with subsequent FS suggests that higher mean HAI will eventually translate into more advanced stages of fibrosis. Patients at risk for more severe post-LT recurrence of HCV can be identified by early posttransplant HCV-RNA levels. [source] Virus load dynamics of individual CMV-genotypes in lung transplant recipients with mixed-genotype infectionsJOURNAL OF MEDICAL VIROLOGY, Issue 8 2008Irene Görzer Abstract Human cytomegalovirus (CMV) is a major cause of disease and transplant dysfunction in lung transplant recipients. Simultaneous emergence of more than one CMV-genotype can occur, and appears to be disadvantageous for the patient. In this study, the dynamics of individual CMV-genotypes in blood and lung was assessed within mixed CMV-genotype populations emerging after lung transplantation. In 69 plasma and 76 bronchoalveolar lavage samples of 16 lung transplant recipients with mixed CMV-genotype infections within the first year posttransplantation each of the major glycoprotein B (gB) and glycoprotein H (gH) genotypes was selectively quantified by genotype-specific quantitative TaqMan assays. The data obtained revealed that individually different genotype dynamics occurred for the individual patients and that the relative levels of the genotypes to each other may change over time. The quantitative development was independent of the specific gB,gH-genotype. In 10 of the 16 lung recipients the patient's individual genotype composition was the same in blood and lung. Genotype development during the follow-up was influenced by antiviral treatment. These data show for the first time that the CMV load used as diagnostic tool after transplantation is not always a constant entity but reflects the sum of the individual CMV-genotype dynamics developing over time. J. Med. Virol. 80:1405,1414, 2008. © 2008 Wiley-Liss, Inc. [source] Overexpression of Bcl-XL in human neural stem cells promotes graft survival and functional recovery following transplantation in spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2009Seung I. Lee Abstract Transplantation of neural stem cells (NSCs) has shown promise for improving functional recovery after spinal cord injury (SCI). The inhospitable milieu of injured spinal cord, however, does not support survival of grafted NSCs, reducing therapeutic efficacy of transplantation. The present study sought to examine whether overexpression of antiapoptotic gene Bcl-XL in NSCs could promote graft survival and functional recovery following transplantation in rat contusive SCI model. A human NSC line (HB1.F3) was transduced with a retroviral vector encoding Bcl-XL to generate Bcl-XL -overexpressing NSCs (HB1.F3.Bcl-XL). Overexpression of Bcl-XL conferred resistance to staurosporine-mediated apoptosis. The number of HB1.F3.Bcl-XL cells was 1.5-fold higher at 2 weeks and 10-fold higher at 7 weeks posttransplantation than that of HB1.F3 cells. There was no decline in the number of HB1.F3.Bcl-XL cells between 2 and 7 weeks, indicating that Bcl-XL overexpression completely blocked cell death occurring between these two time points. Transplantation of HB1.F3.Bcl-XL cells improved locomotor scores and enhanced accuracy of hindlimb placement in a grid walk. Approximately 10% of surviving NSCs differentiated into oligodendrocytes. Surviving NSCs produced brain-derived neurotrophic factor (BDNF), and the level of BDNF was significantly increased only in the HB1.F3.Bcl-XL group. Transplantation of HB1.F3.Bcl-XL cells reduced cavity volumes and enhanced white matter sparing. Finally, HB1.F3.Bcl-XL grafts enhanced connectivity between the red nucleus and the spinal cord below the lesion. These results suggest that enhancing graft survival with antiapoptotic gene can potentiate therapeutic benefits of NSC-based therapy for SCI. © 2009 Wiley-Liss, Inc. [source] Meta-analysis of risk for relapse to substance use after transplantation of the liver or other solid organs,LIVER TRANSPLANTATION, Issue 2 2008Mary Amanda Dew For patients receiving liver or other organ transplants for diseases associated with substance use, risk for relapse posttransplantation is a prominent clinical concern. However, there is little consensus regarding either the prevalence or risk factors for relapse to alcohol or illicit drug use in these patients. Moreover, the evidence is inconsistent as to whether patients with pretransplantation substance use histories show poorer posttransplantation medical adherence. We conducted a meta-analysis of studies published between 1983 and 2005 to estimate relapse rates, rates of nonadherence to the medical regimen, and the association of potential risk factors with these rates. The analysis included 54 studies (50 liver, 3 kidney, and 1 heart). Average alcohol relapse rates (examined only in liver studies) were 5.6 cases per 100 patients per year (PPY) for relapse to any alcohol use and 2.5 cases per 100 PPY for relapse with heavy alcohol use. Illicit drug relapse averaged 3.7 cases per 100 PPY, with a significantly lower rate in liver vs. other recipients (1.9 vs. 6.1 cases). Average rates in other areas (tobacco use, immunosuppressant and clinic appointment nonadherence) were 2 to 10 cases per 100 PPY. Risk factors could be examined only for relapse to any alcohol use. Demographics and most pretransplantation characteristics showed little correlation with relapse. Poorer social support, family alcohol history, and pretransplantation abstinence of ,6 months showed small but significant associations with relapse (r = 0.17-0.21). Future research should focus on improving the prediction of risk for substance use relapse, and on testing interventions to promote continued abstinence posttransplantation. Liver Transpl 14:159,172. 2008. © 2008 AASLD. [source] Employment and quality of life in liver transplant recipientsLIVER TRANSPLANTATION, Issue 9 2007Sammy Saab The purposes of liver transplantation (LT) include the extension of survival, improvement in quality of life, and the return of the recipient as a contributing member of society. Employment is one measure of the ability to return to society. The aim of this study is to determine the factors affecting employment/subemployment after LT. A total of 308 adult liver transplant recipients who were seen at the University of California, Los Angeles were administered the Medical Outcomes Short Form 36 (SF-36) and a questionnaire regarding work history and insurance coverage. Multivariate analysis were used to identify independent variables associated with posttransplantation employment. Interaction terms were used to examine effect modification. Of 308 transplant recipients, 218 (70.8%) worked prior to transplantation, and 78 (27%) worked posttransplantation. Pretransplant variables that were independently associated with posttransplantation employment included the following: lack of disability income (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.32-7.18; P = 0.36); health maintenance organization (HMO)/preferred provider organization (PPO) insurance (OR = 3.08; 95% CI, 1.32-7.18; P < 0.01); the number of hours worked (OR = 1.17; 95% CI, 1.08-1.28; P < 0.01); and the lack of diabetes mellitus (OR = 0.23; 95% CI, 0.70-0.73; P < 0.01). An interaction term between disability income and hours worked prior to transplantation (OR = 0.16; 95 % CI, 0.03-0.83; P = 0.03) was independently associated with posttransplantation employment. In a separate regression model of SF-36 responses, posttransplantation physical functioning (OR = 1.17; 95% CI, 1.10-1.26; P < 0.01) and role-physical (OR = 1.1; 95% CI, 1.02-1.16; P < 0.01) were independently associated with employment after transplantation. In conclusion, HMO or PPO insurance, lack of disability income coverage prior to transplant, the absence of diabetes mellitus, the number of hours worked prior to transplantation, and high physical functioning were associated with posttransplantation employment. Liver Transpl 13:1330,1338, 2007. © 2007 AASLD. [source] Exploring the bidirectional interactions between human cytomegalovirus and hepatitis C virus replication after liver transplantationLIVER TRANSPLANTATION, Issue 1 2007Gaia Nebbia Recurrence of Hepatitis C (HCV) post-liver transplantation (LT) is universal and its course is more aggressive than in immunocompetent individuals. Human cytomegalovirus (CMV) infection is a common post-LT infection and has immunomodulatory effects that could adversely affect the outcome of HCV. To date, the effect of HCV replication on the dynamics of CMV have not been investigated. From 2000 to 2004, a cohort of 69 HCV-infected liver transplant recipients and 188 HCV-negative liver transplant recipients (NON-HCV cohort) were monitored for CMV infection twice weekly by CMV polymerase chain reaction (PCR) with preemptive therapy initiated after 2 consecutive positive results. None of the patients received CMV prophylaxis. A subset of 18 HCV-infected patients had their HCV viral load monitored regularly post-LT by quantitative PCR. CMV DNAemia (>200 genomes/mL blood) did not influence the level of HCV replication within 150 days posttransplantation or the stage of liver fibrosis in liver biopsies at 1 yr post-LT. There were no differences in the incidence of CMV DNAemia or replication dynamics in the HCV cohort compared to the NON-HCV cohort. In conclusion, short term CMV viremia does not enhance the replication of HCV after LT, while HCV replication does not alter the replication dynamics of CMV. Liver Transpl 13:130,135, 2007. © 2006 AASLD. [source] Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: The Kyoto experienceLIVER TRANSPLANTATION, Issue 8 2006Yasumasa Shirouzu Smaller-size infants undergoing living-donor liver transplantation (LDLT) are at increased risks of vascular complications because of their smaller vascular structures in addition to vascular pedicles of insufficient length for reconstruction. Out of 585 child patients transplanted between June 1990 and March 2005, 64 (10%) weighing less than 6 kg underwent 65 LDLTs. Median age and weight were 6.9 months (range: 1-16 months) and 5 kg (range: 2.8-5.9 kg), respectively. Forty-five lateral segment, 12 monosegment, and 8 reduced monosegment grafts were adopted, and median graft-to-recipient weight ratio was 4.4% (range: 2.3-9.7). Outflow obstruction occurred in only 1 patient (1.5%). Portal vein complication occurred in 9 (14%) including 5 with portal vein thrombosis. Hepatic artery thrombosis (HAT) occurred in 5 (7.7%). Patient and graft survivals were 73% and 72% at 1 yr, and 69% and 68% at 5 yr after LDLT, respectively. Thirteen of 22 grafts (58%) lost during the follow-up period occurred within the first 3 months posttransplantation. Overall graft survival in patients with and without portal vein complication was 67% and 65%, respectively (P = 0.54). Overall graft survival in patients with and without HAT was 40% and 67%, respectively. HAT significantly affected graft survival (P = 0.04). In conclusion, our surgical technique for smaller-size recipients resulted in an acceptable rate of vascular complications. Overcoming early posttransplantation complications will further improve outcomes in infantile LDLT. Liver Transpl 12:1224,1232, 2006. © 2006 AASLD. [source] The role of immunosuppression in recurrence of hepatitis CLIVER TRANSPLANTATION, Issue 11 2003John R. Lake Key points 1. Recurrent hepatitis C is an increasing problem posttransplantation. 2. It is difficult to determine histologically if alloimmunity, i.e., rejection, is also plays a role in posttransplantation hepatitis C. 3. Change in the degree of immunosuppression, rather than the absolute amount of immunosuppression, is bad for HCV-infected recipients. 4. Corticosteroid boluses are bad for HCV-infected recipients. [source] Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-upLIVER TRANSPLANTATION, Issue 6 2003Paul Greig Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone ,0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P = .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P = .052). Graft survival was 97% and 86%, respectively (P = .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P = .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis. [source] Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidatesLIVER TRANSPLANTATION, Issue 4 2002Gary A. Abrams MD Assistant Professor of Medicine Hepatopulmonary syndrome, arterial hypoxemia caused by intrapulmonary vasodilatation, occurs in approximately 10% of patients with cirrhosis. The severity of hypoxemia affects liver transplant candidacy and is associated with increased morbidity and mortality posttransplantation. Screening guidelines for detecting the presence of arterial hypoxemia do not exist. The aim of this study is to investigate the accuracy and utility of pulse oximetry in the detection of hypoxemia (PaO2 < 70 mm Hg) in patients with cirrhosis. Two hundred prospective liver transplant candidates were compared with 94 controls. Arterial oxyhemoglobin saturation was obtained by pulse oximetry (SpO2) and compared with simultaneous arterial blood gas (ABG) oxyhemoglobin values (SaO2; bias = the difference). PaO2, carboxyhemoglobin, methemoglobin, and routine clinical and biochemical parameters were investigated to account for the bias. SpO2 overestimated SaO2 in 98% of patients with cirrhosis (mean bias, 3.37%; range, ,1% to 10%). Forty-four percent of patients with cirrhosis and controls had a bias of 4% or greater. No clinical or biochemical parameters of cirrhosis accounted for the overestimation of pulse oximetry. Twenty-five subjects with cirrhosis were hypoxemic, and an SpO2 of 97% or less showed a sensitivity of 96% and a positive likelihood ratio of 3.9 for detecting hypoxemia. An SpO2 of 94% or less detected all subjects with an arterial PaO2 less than 60 mm Hg. Pulse oximetry significantly overestimates arterial oxygenation, and the inaccuracy is not influenced by liver disease. Nevertheless, pulse oximetry can be a useful screening tool to detect arterial hypoxemia in patients with cirrhosis, but a higher threshold for obtaining an ABG must be used. [source] Fitness testing of pediatric liver transplant recipientsLIVER TRANSPLANTATION, Issue 3 2001Viswanath B. Unnithan PhD Liver transplantation is accepted as the standard management for end-stage liver disease in children. Pediatric heart and heart-lung transplant recipients have shown significantly diminished exercise capacities compared with age-matched, able-bodied, control subjects. The primary aim of this study is to compare the fitness levels of a group of pediatric liver transplant (LT) recipients (LT group, 20 boys, 9 girls; age, 8.9 ± 4.8 years; 56 ± 35 months posttransplantation) with a group of able-bodied control subjects (22 boys, 12 girls; age, 8.4 ± 3.8 years). The secondary aim is to compare the performance of the LT group against the Fitnessgram criterion standards. We assessed muscular endurance by means of a partial curl-up, flexibility by means of the back-saver sit and reach, and cardiorespiratory fitness by means of the progressive aerobic cardiovascular endurance run (PACER). The only significant (P < .05) difference between the 2 groups was the number of shuttles run in the PACER (control, 16.8 ± 9.8 v LT, 11.5 ± 8.4 shuttles). Other differences between the 2 groups were not significant. With regard to satisfying the Fitnessgram criterion standards, only 35% of the LT group achieved the standards for the partial curl-up, 88% of the LT group achieved the criterion standards for flexibility, and 0% achieved the standards for the PACER. These results indicate that the LT group has diminished exercise capacity. The origins of exercise limitations deserve further investigation. [source] Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudineLIVER TRANSPLANTATION, Issue 6 2000Craig A. Sponseller Lamivudine is effective in inhibiting hepatitis B virus (HBV) replication, and its clinical use in patients with chronic hepatitis B is associated with improvements in serum aminotransferase levels and liver histopathologic characteristics. Few data are available on its use in patients with advanced liver disease. We report on the outcomes of 5 patients with hepatic decompensation caused by chronic hepatitis B treated long term with lamivudine. All patients were adult white men seropositive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) before therapy. All 5 patients had biopsy-proven cirrhosis with clinical and biochemical evidence of hepatic decompensation. Two patients had Child's class C cirrhosis; 2 patients, class B; and 1 patient, class A (although this patient had persistent portasystemic encephalopathy and developed variceal bleeding). HBV DNA became undetectable in all patients and remained so throughout the study. Both patients with Child's class C and 1 patient with class B cirrhosis had significant clinical improvement. Child-Pugh scores improved from 12 to 7 and 11 to 7 in the 2 patients with Child's class C cirrhosis, and the patient with class B cirrhosis had complete resolution of troublesome encephalopathy. Serum aminotransferase, albumin, and total bilirubin levels improved significantly in 3 of 5 patients. One patient with Child's class B cirrhosis underwent orthotopic liver transplantation at week 13 after dramatic increases in liver tests and clinical worsening. The patient subsequently cleared HBeAg and HBsAg from serum posttransplantation. In conclusion, prolonged therapy with lamivudine resulted in improved serum biochemical values and loss of HBV DNA in patients with decompensated cirrhosis. Clinical improvements, reflected in Child-Pugh classification and functional status, may also occur, particularly among those with Child's class C disease initially. [source] Quality of life after liver transplantation for alcoholic liver diseaseLIVER TRANSPLANTATION, Issue 6 2000Stephen P. Pereira There are few data on predictive factors for alcohol relapse or long-term functional outcome after liver transplantation for alcoholic liver disease (ALD). In all 56 surviving UK patients (47 men, 9 women; mean age: 51 years; range: 33 to 69 years) who underwent transplantation for ALD at King's College Hospital over a 10-year period, alcohol relapse and outcome were assessed by outpatient and case-note review and by postal questionnaire containing (1) the Nottingham Health Profile (NHP), (2) the Short-Form-36 (SF-36) Health Survey, and (3) a drug and alcohol questionnaire. At a median of 2.5 years (range: 0.5 to 10 years), 13 of the 47 respondents (28%) and 2 of the 9 nonrespondents (22%) had evidence of potentially harmful drinking (>3 units daily) at some time posttransplantation. An additional 13 patients admitted to drinking some alcohol at least once, corresponding to an overall relapse rate of 50%. The patients with harmful drinking (1) had started drinking regularly at a younger age (18 v 25 years; P = .01), (2) began drinking heavily at a younger age (30 v 40 years; P = .01), (3) had shorter pretransplantation abstinence periods (10 v 23 months; P = .02), and (4) had a longer time since transplantation (median, 5.7 v 1.5 years; P = .0004) than those with no or mild alcohol relapse. They were also more likely to report sleep disturbance (NHP sleep problem score, 45 v 16; P = .01) and use benzodiazepines regularly (7 of 13 v 3 of 34 patients; P = .002). Despite these differences, health dimension scores in the SF-36 and NHP posttransplantation were similar between the groups and to those of UK community controls. In the long term, at least 50% of the patients will drink again at some time posttransplantation, although at lower levels of alcohol intake than previously. Those patients with multiple predictive factors for alcohol relapse may be at greatest risk for harmful drinking and be the group that would benefit most from professional counseling. Overall, the quality of life after liver transplantation for ALD is high and broadly similar to the levels expected in the normal population. [source] Rapid method for the analysis of peripheral chimerism in suspected graft-versus-host disease after liver transplantationLIVER TRANSPLANTATION, Issue 2 2000Amy B. Hahn The effects of microchimerism and possible tolerance have been well studied in orthotopic liver transplantation. In some patients, greater levels of donor cells persist in the periphery. These cells were characterized and their effects on clinical outcome were studied. Peripheral blood was obtained from patients at various times posttransplantation. HLA class II typing was performed by the polymerase chain reaction,sequence-specific primer method on unfractionated blood and lymphocyte subpopulations. Relative levels of amplification of donor and recipient alleles were compared. All patients studied had a low degree of chimerism that was most apparent in the CD8+T/natural killer (NK) cell population. One patient with persistently high levels of donor alleles in his CD8+T/NK cell population was diagnosed with severe graft-versus-host disease (GVHD) and died of opportunistic infections. Another patient with biopsy-proven GVHD was chimeric in several cell populations. On resolution of her symptoms, donor alleles were reduced to levels undetectable by this assay. These results suggest that persistently elevated levels of donor CD8+T/NK cells in the periphery may indicate GVHD in liver transplant recipients. This technique aids in rapid diagnosis, which facilitates appropriate treatment and thus may improve clinical outcome. [source] Significance of detecting epstein-barr,specific sequences in the peripheral blood of asymptomatic pediatric liver transplant recipientsLIVER TRANSPLANTATION, Issue 1 2000Nancy R. Krieger Pediatric allograft recipients are at increased risk for Epstein-Barr virus (EBV)-associated illnesses. The early identification and diagnosis of EBV-associated disorders is critical because disease progression can often be curtailed by modification of immunosuppression. We have previously shown that detection of EBV-specific sequences in the circulation by polymerase chain reaction (PCR) correlated well with the clinical symptoms of EBV infection. The purpose of the current study is to determine the significance of detecting EBV-specific sequences by PCR in asymptomatic pediatric liver transplant recipients. Peripheral-blood DNA was analyzed for the EBV genes, coding from the nuclear antigen 1 (EBNA-1) and the viral capsid antigen (gp220) by PCR. Samples from asymptomatic pediatric liver transplant recipients were analyzed from the immediate postoperative period and at 2- to 4-month intervals thereafter. We followed up 13 of these asymptomatic recipients who tested positive for EBV compared with 7 asymptomatic recipients who tested negative for EBV during the early posttransplantation period. Follow-up ranged from 1.5 to 4 years posttransplantation. Nine patients (69%) initially positive for EBV and asymptomatic ultimately developed symptoms of EBV infection, including fever, lymphadenopathy, rash, respiratory and gastrointestinal symptoms, and/or hepatitis. Five of these patients (56%) went on to develop posttransplant lymphoproliferative disorder based on histological examination of biopsied tissue and immunohistochemical identification of the EBV antigen/DNA in tissue. This is the first report suggesting that detection of EBV-specific sequences in the absence of symptoms may herald impending EBV-associated disorders. Thus, routine monitoring for circulating EBV sequences in asymptomatic recipients may be useful in the early identification of those at risk for developing EBV-associated disease and its ultimate prevention. (Liver Transpl 2000;6:62-66.) [source] Transplanted dopaminergic neurons develop PD pathologic changes: A second case report,MOVEMENT DISORDERS, Issue 16 2008Jeffrey H. Kordower PhD Abstract This report describes pathological changes within the grafted neurons of another patient with Parkinson's disease (PD) who died 14 years posttransplantation. Although numerous healthy appearing grafted neurons were present at this long-term time point, some displayed Lewy bodies as evidenced by alpha-synuclein, ubiquitin, and thioflavin-S staining. Additionally, there was a general loss of dopamine transporter-immunoreactivity in grafted neurons. Some grafted cell displayed a loss of tyrosine hydroxylase. These data support the emerging concept that PD-like pathology is seen in young grafted neurons when they survive long term. © 2008 Movement Disorder Society [source] The Molecular Phenotype of Heart Transplant Biopsies: Relationship to Histopathological and Clinical VariablesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010M. Mengel Histopathology of endomyocardial biopsies (EMB) is the standard rejection surveillance for heart transplants. However, ISHLT consensus criteria for interpreting biopsies are arbitrarily defined. Gene expression offers an independent re-evaluation of existing diagnostic systems. We performed histologic and microarray analysis on 105 EMB from 45 heart allograft recipients. Histologic lesions, diagnosis and transcripts were compared to one another, time posttransplantation, indication for biopsy and left ventricular ejection fraction (LVEF). Histologic lesions presented in two groups: myocyte,interstitial and microcirculation lesions. Expression of transcript sets reflecting T cell and macrophage infiltration, and ,-interferon effects correlated strongly with each other and with transcripts indicating tissue/myocardium injury. This molecular phenotype correlated with Quilty (p < 0.005), microcirculation lesions (p < 0.05) and decreased LVEF (p < 0.007), but not with the histologic diagnosis of rejection. In multivariate analysis, LVEF was associated (p < 0.03) with ,-interferon inducible transcripts, time posttransplantation, ischemic injury and clinically indicated biopsies, but not the diagnosis of rejection. The results indicate that (a) the current ISHLT system for diagnosing rejection does not reflect the molecular phenotype in EMB and lacks clinical relevance; (b) the interpretation of Quilty lesions has to be revisited; (c) the assessment of molecules in heart biopsy can guide improvements of current diagnostics. [source] Case Report: Combined Pancreas and En Bloc Kidney Transplantation Using a Bladder Patch Technique From Very Small Pediatric DonorsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010J. Sageshima Very small pediatric donors are underutilized for pancreas and kidney transplantation for the fear of inadequate islet mass and higher incidence of technical complications, and the lower age limit for such donors is not well defined. We present here two cases of combined pancreas and en bloc kidney transplantation from very small pediatric donors (14 and 18 months old) to adult type 1 diabetic and uremic patients. The conventional surgical procedure for simultaneous pancreas and kidney transplantation with systemic venous and bladder exocrine drainage was successfully applied to very small organs. For both, we utilized the recently described bladder patch technique for ureteral reconstruction. One patient developed venous thrombosis (partial thrombosis of the splenic and mesenteric veins) and the other urine leak (from a midportion of the medial ureter without compromising the bladder patch) after the transplants; both were successfully managed and the patients demonstrated immediate and sustained pancreas and kidney graft functions for 12 and 2 months posttransplantation. These cases illustrate the feasibility of combined pancreas and en bloc kidney transplantation from very small pediatric donors using a bladder patch technique to avoid small ureteral anastomosis. [source] High Dose Epoetin Beta in the First Weeks Following Renal Transplantation and Delayed Graft Function: Results of the Neo-PDGF StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010F. Martinez Erythropoietin promotes nephroprotection in animal models of ischemia-reperfusion injury. Neorecormon® and Prevention of Delayed Graft Function (Neo-PDGF) is a French open-label multicenter randomized study to evaluate the effect of high doses of epoetin beta (EPO-,) during the first 2 weeks of renal transplantation on renal function in patients at risk for delayed graft function (DGF). One hundred and four patients were included in the study. Patients randomized in treatment group (A) received four injections of EPO-, (30.000 UI each), given before surgery and at 12 h, 7 days and 14 days posttransplantation. Patients randomized in control group (B) did not receive EPO-,. Immunosuppression included induction with basiliximab and maintenance therapy with steroids, mycophenolate mofetil and tacrolimus. At 1 month posttransplant, the estimated glomerular filtration rate (MDRD formula) was 42.5 ± 19.0 mL/min in the EPO-, group and 44.0 ± 16.3 mL/min in the control group (p = ns). The frequency of DGF was similar in both groups (32% vs. 38.8%; p = ns). No difference in the incidence of serious adverse events was observed. (ClinicalTrials.gov number, NCT00815867.) [source] Extracorporeal Support: Improves Donor Renal Graft Function After Cardiac DeathAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010A. Rojas-Pena Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4,6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min ± 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min ± 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h ± 1.7). DCD-30 had lower CrCl (0.9 mL/min ± 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI. [source] Melanoma in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010F. O. Zwald This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM. [source] Receptor for Advanced Glycation End Products in Donor Lungs Is Associated with Primary Graft Dysfunction After Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010A. Pelaez Development of primary graft dysfunction (PGD) is associated with poor outcomes after transplantation. We hypothesized that Receptor for Advanced Glycation End-products (RAGE) levels in donor lungs is associated with the development of PGD. Furthermore, we hypothesized that RAGE levels would be increased with PGD in recipients after transplantation. We measured RAGE in bronchoalveolar lavage fluid (BALf) from 25 donors and 34 recipients. RAGE was also detected in biopsies (transbronchial biopsy) from recipients with and without PGD. RAGE levels were significantly higher in donor lungs that subsequently developed sustained PGD versus transplanted lungs that did not display PGD. Donor RAGE level was a predictor of recipient PGD (odds ratio = 1.768 per 0.25 ng/mL increase in donor RAGE level). In addition, RAGE levels remained high for 14 days in those recipients that developed severe graft dysfunction. Recipients may be at higher risk for developing PGD if they receive transplanted organs that have higher levels of soluble RAGE prior to explantation. Moreover, the clinical and pathologic abnormalities associated with PGD posttransplantation are associated with increased RAGE expression. These findings also raise the possibility that targeting the RAGE signaling pathway could be a novel strategy for treatment and/or prevention of PGD. [source] Neurological Complications Following Adult Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010F. J. Mateen The full spectrum of neurologic complications and their impact on survival in lung recipients has not been reported. A retrospective cohort review of the Mayo Clinic Lung Transplant Registry (1988,2008) was performed to determine the range of neurologic complications in a cohort of adult lung recipients. Cox regression models were used to assess risk factors for neurological complications and death posttransplant. One hundred and twenty lung transplant recipients (53% women, median age at transplantation 53 years, range 21,73, median survival 4.8 years) were identified, of whom 95 had a neurological complication posttransplantation (median time to complication 0.8 years). Neurological complications were severe in 46 patients (requiring hospitalization or urgent care and evaluation) and were most often perioperative stroke or encephalopathy. Age predicted neurological complications of any type, whereas lung allocation score, bilateral lung transplantation, sex, underlying lung disease, elevated hemoglobin A1C, renal insufficiency and smoking history did not. Neurological complications of any severity (HR 4.3, 95% CI 2.2,8.6, p < 0.001) and high severity (HR 7.2, 95% CI 3.5,14.6, p < 0.001) were associated with increased risk of death. Neurological complications are common after lung transplantation, affecting 92% of recipients within 10 years. Severe neurologic complications are also common, affecting 53% of recipients within 10 years. [source] | |||||||||||||