Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis.

Impact of simultaneous pancreas-kidney transplantation: patients' perspectives

Background: Few qualitative studies of simultaneous pancreas-kidney transplantation (SPK Tx) have been published. The aims of this study were to explore from the perspective of patients, the experience of living with diabetes mellitus type 1 (T1DM), suffering from complications, and undergoing SPK Tx with good outcome; and to determine the impact of SPK Tx on patients and their social and cultural environment. Methods: We performed a focused ethnographic study. Twenty patients were interviewed. Data were analyzed using content analysis and constant comparison following the method proposed by Miles and Huberman. Results: A functioning SPK Tx allowed renal replacement therapy and insulin to be discontinued. To describe their new situation, patients used words and phrases such as "miracle", "being reborn" or "coming back to life". Although the complications of T1DM, its surgery and treatment, and associated psychological problems did not disappear after SPK Tx, these were minimized when compared with the pretransplantation situation. Conclusion: For patients, SPK Tx represents a recovery of their health and autonomy despite remaining problems associated with the complications of T1DM and SPK Tx. The understanding of patients' existential framework and their experience of disease are key factors for planning new intervention and improvement strategies.

Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview

Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation

First Annual IMACS Report: A global International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support

The first annual report of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) registry provides global data on 5,942 patients from 31 countries. This initial report focuses on patient demographics, survival, device types, adverse events, competing outcomes, and a risk factor analysis.

Histoire de la Littérature Grecque profane, depuis son origine jusquʾa la prise de Constantinople par les turcs : suivie d'un précis de lʾhistoire de la transplantation de la littérature grecque en occident /

Includes bibliography and index.

Organ transplantation : issues and recommendations /

Reports for <1997- > also called <34d- >.

Die heteroplastische und homöoplastische Transplantation; eigene Untersuchungen und vergleichende Studien.

Contains bibliography.

The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation

Purpose. The aim of this study was to report the influence of hepatitis C virus (HCV) genotype and rejection episodes on the outcome of orthotopic liver transplantation (OLT), hepatitis recurrence, and progression to graft cirrhosis after OLT. Methods. Fifty-three patients who all had undergone OLT for end-stage liver cirrhosis were selected for this study. Hepatitis C genotype was determined. Recurrent hepatitis and rejection were diagnosed based on elevated liver function tests and a liver biopsy. Results. The patients were followed up for a mean of 51.9 +/- 34.3 months. The cumulative survival rate was no different in OLT for hepatitis C and OLT for all other liver diseases. After OLT, serum HCV RNA was detected in 93%. Histological recurrence occurred in 85% of all patients. The 1-, 3-, and 5-year recurrence rates were 48%, 77%, and 85%, respectively. Of the 41 patients with recurrent hepatitis C, 4 (10%) had cirrhosis, 18 (44%) had hepatitis with fibrosis, and 91 (46%) had hepatitis without fibrosis at the end of follow-up. A total of 32% of the patients were infected by HCV genotype 1b and 68% by other HCV genotypes. The recurrence rates were significantly higher in patients infected with genotype 1b than in those with other genotypes (p = 0.04). Twenty of 48 patients (42%) experienced acute rejection. There was a strong association between the number of rejection episodes and the incidence of HCV-related cirrhosis (p < 0.01). Conclusion. Our findings showed the genotype 1b to result in a higher recurrence rate after OLT. On the other hand, rejection episodes were associated with a more rapid progression to graft cirrhosis.

Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation

The granulocyte colony-stimulating factor (G-CSF) and Fit-3 receptor agonist progenipoietin-1 (ProGP-1) has potent effects on dendritic cell (DC) expansion and may be an alternative to G-CSF for the mobilization of stem cells for allogeneic stem cell transplantation (SCT). We studied the ability of stem cell grafts mobilized with this agent to induce graft-versus-host disease (GVHD) to minor and major histocompatibility antigens in the well-described B6 --> B6D2F1 SCT model. ProGP-1, G-CSIF, or control diluent was administered to donor B6 mice. ProGP-1 expanded all cell lineages in the spleen, and unseparated splenocytes from these animals produced large amounts of interleukin 10 (IL-10) and transforming growth factor beta (TGFbeta) whereas the expression of T-cell adhesion molecules was diminished. Transplantation survival was 0%, 50%, and 90% in recipients of control-, G-CSF-, and ProGP-1-treated allogeneic donor splenocytes, respectively (P < .0001). Donor pretreatment with ProGP-1 allowed a 4-fold escalation in T-cell dose over that possible with G-CSF. Donor CD4 T cells from allogeneic SCT recipients of ProGP-1 splenocytes demonstrated an anergic response to host antigen, and cytokine production (interferon gamma [IFNγ], IL-4, and IL-10) was also reduced while CD8 T-cell cytotoxicity to host antigens remained intact. Neither CD11c(hi) DCs nor CD11c(dim)/B220(hi) DCs from ProGP-1-treated animals conferred protection from GVHD when added to control spleen. Conversely, when equal numbers of purified T cells from control-, G-CSF-, or ProGP-1-treated allogeneic donors were added to allogeneic T-cell-depleted control spleen, survival at day 60 was 0%, 15%, and 90%, respectively (P < .0001). The improved survival in recipients of ProGP-1 T cells was associated with reductions in systemic tumor necrosis factor alpha generation and GVHD of the gastrointestinal tract. We conclude that donor pretreatment with ProGP-1 is superior to G-CSIF for the prevention of GVHD after allogeneic SCT, primarily due to incremental affects on T-cell phenotype and function

Liver transplantation for HCV-associated liver cirrhosis: Predictors of outcomes in a population with significant genotype 3 and 4 distribution

End-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, reinfection of the graft is universal. We aimed to determine predictors of outcome of HCV-Iiver transplant recipients in the Australian and New Zealand communities. The following variables were analysed: demographic factors, coexistent pathology at the time of transplantation, HCV genotype, and donor age. Outcomes measures were: 1. mortality; 2. development of HCV-related complications, which were stage 3 or 4 fibrosis, or mortality from HCV-related graft failure, or both. Between January 1989 and December 30, 1999, 182 patients were transplanted for HCV-associated cirrhosis. The median follow-up period was 4 years (range, 0 to 13 years). Genotype data were available on 157 patients. The distribution of genotypes among the 157 patients was as follows: 36 (23%) genotype la, 30 (19%) genotype 1b, 4 (9%) genotype 1, 17 (11%) genotype 2, 41 (26%) genotype 3a, and 16 (10%) genotype 4. Eight (5%) patients were HCV-polymerase chain reaction (PCR)-negative (but HCV-antibody positive). Donor age and genotype 4 were associated with an increased risk of retransplantation or death (P < .001 and.05, respectively). Meanwhile, donor age, genotype 4, and pretransplant excess alcohol were risk factors for the development of HCV-related complications (P = .004, .008, and .02, respectively). In contrast, patients with genotype 3a were less likely to develop HCV-related complications (P = .05). In a population of HCV liver transplant recipients with a heterogeneous genotype distribution, donor age, and genotype 4, were predictors of a worse outcome, whereas genotype 3 was associated with a more favorable outcome.