Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.

Seven murine monoclonal antibodies (mAb) with different binding characteristics for human IgM varied markedly in their ability to induce proliferation of T cell-depleted human splenocytes. Two mAb (HB57 and 5D7) that bound to distinct epitopes on IgM were highly effective initiators of B cell proliferation at very low concentrations, in the presence of a T cell factor source. In the absence of T cell supernatant, both HB57 and 5D7 mAbs produced a markedly reduced degree of stimulation at all concentrations. Two additional anti-IgM mAb (VIIIE11 and Mu53) were distinctive in that, even at high concentrations, only limited proliferation was observed compared with the first group of mAb. This proliferation depended on the presence of T cell supernatant. Competitive-binding studies revealed that the epitope recognized by mAb Mu53 may be identical or very proximate to that recognized by HB57. Three other mAb (1G6, XG9, and P24) induced little or no proliferation. 1G6 bound to a unique epitope on the IgM molecule, whereas XG9 shared a determinant with VIIIE11 mAb. Regulatory influences of Fc receptor binding cannot account for all the diversity in proliferation observed with the individual anti-IgM mAb. Markedly augmented proliferation was obtained when B cells were cultured with certain combinations of anti-IgM mAb in the presence of exogenous T cell supernatant. The proliferation induced in the absence of T cell supernatant by high concentrations of mAb mixtures that included 1G6 approached that observed for the same mixtures in the presence of T cell supernatant. The data suggest that certain signals delivered through membrane IgM can bypass the need for T cell supernatant in the activation of human B lymphocytes.

Anti-IgM-mediated B cell signaling. Molecular analysis of ligand binding requisites for human B cell clonal expansion and tolerance.

The ligand binding requisites for membrane IgM-mediated signaling of human B lymphocyte clonal expansion and B cell tolerance were investigated with a well-characterized set of soluble murine anti-human IgM mAbs. Evaluation of the impact of mu chain domain specificity, affinity, and binding stoichiometry for membrane IgM on antibody-induced regulation of normal and leukemic B cell DNA synthesis revealed that the ligand binding requisites for inducing or, alternatively, suppressing B cell DNA synthesis are significantly different. First, while the induction of S phase entry required micrograms/ml concentrations of ligand, orders of magnitude lower concentrations of ligand sufficed for inhibitory signaling. Second, while an upper affinity threshold for achieving maximal stimulation of B cell DNA synthesis was never detected, inhibitory signaling by bivalent ligands appeared to become relatively affinity independent at Fab binding affinities greater than 7.0 x 10(6) M-1. Third, while a C mu 1-specific mAb with an enhanced incidence of monogamous binding to mIgM was ineffective at inducing B cell DNA synthesis, the antibody was not significantly compromised in ability to initiate inhibitory signals. These differences could be observed in a clonal B cell population which positively or negatively responded to mIgM ligation depending upon its state of activation. The accumulated observations indicate that the ligand binding requisites for inhibitory signal transduction in human B lymphocytes are much less rigorous than those for stimulatory signal transduction and suggest that many physiologically relevant anti-Ig antibodies are more likely to function in the negative feedback regulation of B cell responses than in the direct triggering of human B cell clonal expansion.

Temperature dependence of ADH-induced water flow and intramembranous particle aggregates in toad bladder.

Antidiuretic hormone (ADH)-induced luminal intramembranous particle aggregates and hormonally stimulated water flow in toad urinary bladder are reduced simultaneously with a reduction in temperature. When water movement is factored by the aggregation response, the apparent activation energy for this process decreases from 12.1 +/- 1.6 to 3.0 +/- 2.3 kilocalories per mole. The data are consistent with the view that the particle aggregates contain sites for transmembrane water movement and that these sites behave as pores.

Donors after cardiac death: validation of identification criteria (DVIC) study for predictors of rapid death.

Donation after cardiac death (DCD) is uncommon in part because clinicians cannot prospectively identify patients who are likely to die within 60 min of withdrawal of life-sustaining treatments (LST). UNOS criteria exist but have not been validated. Consecutive patients electively withdrawn from LST at five university-affiliated hospitals were prospectively enrolled. Demographic and treatment characteristics were collected. Chi-square was used to determine risk for death within 60 min and validate the UNOS criteria. A total of 533 patients were enrolled. A total of 28 were excluded from this report due to age <18 years or failure to include time of death. Of 505 (95%) patients, 227 (45%) died within 60 min, 134 (27%) in 1-6 h and 144 (29%) >6 h after withdrawal of LST. A total of 29%, 52%, 65% and 82% of patients with 0,1,2 and 3 UNOS DCD criteria, respectively, died within 60 min of withdrawal of LST. The data validate the UNOS criteria. Patients with no criteria might be excluded from consideration for DCD. Those with more than one criterion are reasonable candidates, while those with a single criterion should be considered if a 50% failure rate for DCD is acceptable.

Methicillin-resistant Staphylococcus aureus infection in liver transplantation: a matched controlled study.

UNLABELLED: The purpose of this study was to evaluate the clinical impact of methicillin-resistant Staphylococcus aureus (MRSA) infections on transplant recipients. METHODS: Liver and kidney recipients with MRSA infections were retrospectively identified and compared to an age, gender, UNOS status, organ transplanted, and transplant date matched (2:1) non-MRSA-infected recipient control group. All MRSA infections were initially treated with vancomycin, and four (33%) liver recipients were converted to linezolid therapy after failing to improve with vancomycin. RESULTS: The overall MRSA infection incidence was 1.4% (24/1770) with MRSA more common in liver (3.75%; 12/320) than kidney transplants (0.8%; 12/1450) (P < .001). The most common sites of MRSA infection were blood (42%), lung (38%), and abdomen (29%). The MRSA group had a greater percentage of prior antibiotic usage (79% vs 40%; P < .0015). The MRSA group experienced more posttransplant complications (52% vs 19%; P < .011)), and exhibited a trend toward greater length of stay in the intensive care unit (7.8 vs 4.6 days; P = .09), but not overall length of stay. Survival was similar in MRSA and non-MRSA groups (75% vs 88%; P = .17). No significant differences in mortality were noted between liver and kidney recipients infected with MRSA (P = .6). CONCLUSION: MRSA infection is associated with a higher incidence of posttransplant complications and antibiotic usage in both liver and kidney recipients compared to patients with MRSA infection.

Pilot study of early corticosteroid elimination after pancreas transplantation.

UNLABELLED: Early corticosteroid withdrawal has recently been shown to be possible in recipients of simultaneous pancreas kidney transplants; however, its feasibility in solitary pancreas recipients has not been documented. In the present study, we provide evidence that early withdrawal can be achieved in pancreas as well as pancreas-kidney recipients. METHODS: Twenty type I diabetics underwent 13 pancreas-kidney transplants and 7 pancreas-only transplants with early withdrawal (methylprednisone 6-day taper). Additional immunosuppression consisted of tacrolimus, mycophenolate mofetil, and thymoglobulin induction (five doses). RESULTS: Transplants included 13 pancreas-kidney, 6 pancreas after kidney transplant, and 1 pancreas after islet transplant. Overall mean follow-up was 7.3 months. One episode of pancreas transplant rejection after pancreas-only transplant was detected on protocol biopsy without biochemical abnormalities. One renal allograft rejection occurred 65 days posttransplant in a pancreas-kidney recipient and was graded as a Banff IA rejection. A single pancreas graft loss occurred due to thrombosis 6 days after pancreas-kidney transplantation. CONCLUSIONS: These results indicate that relatively short thymoglobulin induction (five doses) with tacrolimus and mycophenolate mofetil can allow early withdrawal in both pancreas-kidney and pancreas-only transplant recipients.

The importance of clinical parameters when differentiating cholestatic hepatitis C virus from allograft rejection.

BACKGROUND: The exact cause and appropriate treatment for cholestasis following liver transplantation in recipients with hepatitis C virus recurrence (RHCV) are difficult to determine. Our objective was to determine the diagnostic accuracy of clinical and histological parameters in liver transplant recipients with RHCV and concurrent cholestasis. METHODS: A retrospective analysis from June 1996 to May 2003 was performed on adult liver transplant (OLT) recipients with hepatitis C virus. Patients with cholestasis (bilirubin >5 mg/dL, 6 months after OLT) were selected. Demographics, etiology, immune suppression, clinical and histologic outcomes, and virologic features were evaluated. Patients were divided into two groups based on clinical and histological criteria: (1) patients with parameters suggestive of cholestatic HCV; and (2) patients with parameters consistent with acute cellular rejection. RESULTS: Thirty-seven patients met study criteria (20 males). The average age was 54 years (range = 14-72), and time from transplant to jaundice was 769 days (range = 48-2981). The groups were comparable regarding HCV viral load, age, gender, time from transplant, and United Network of Organ Sharing status at time of transplant. Retransplantation was performed in two patients in group 1, neither of whom survived, and in three patients in group 2, all of whom survived. Clinical parameters correlated well with diagnosis of cholestasis (r = 0.85, P < .001) whereas histological evaluation did not (r = 0.11, P = .53). Mortality in group 1 was 78% (7 of 9) vs. 50% (13 of 26) in group 2. Median duration of survival following liver transplantation in group 1 was 132 days versus 435 days in group 2. CONCLUSION: Clinical diagnosis parameters for RHCV with cholestasis appear more accurate than histology parameters and should be the primary consideration in directing therapy. Despite timely diagnosis, cholestatic RHCV LTx recipients have a poor prognosis.

Analysis of the domain specificity of various murine anti-human IgM monoclonal antibodies differing in human B lymphocyte signaling activity.

The domain binding specificity of 19 murine anti-human IgM monoclonal antibodies (MoAbs) that have shown considerable heterogeneity in the transduction of stimulatory and inhibitory signals to B lymphocytes was evaluated by competition radioimmunoassays. Through the use of: (i) enzymatic fragments of IgM which each encompass more than a single CH domain, i.e. Fc5 mu and F(ab')2 mu, (ii) isolated single domains, C mu 2, C mu 3, and C mu 4, and (iii) mu heavy chain disease proteins, nine anti-IgM MoAbs were found to have C mu 1 domain specificity, five to have C mu 2 specificity, and five others to have C mu 4 specificity. Ineffective binding to isolated mu chain demonstrated that C mu 1-specific MoAbs were directed to epitopes which require light chain for expression. The lack of binding of the C mu 4-specific MoAbs to CNBr cleavage fragments of Fc5 mu suggest that the determinants recognized by these MoAbs may also be conformational in nature. Cross-inhibition analyses were used to determine the number of unique epitopes recognized by the anti-IgM MoAbs. Results from these experiments showed that: (i) eight of the nine MoAbs specific for C mu 1 likely bind to a single epitope, or very proximate epitopes, (ii) the five C mu 2-specific MoAbs recognize at least three distinct epitopes, and (iii) the five C mu 4-specific MoAbs each recognize a separate determinant. A comparison of the known B cell activating properties of these MoAbs with their specificity for the various segments of the IgM molecule indicate that mitogenicity cannot be attributed to selective binding to any one domain.

Interaction of mycophenolate mofetil and HLA matching on renal allograft survival.

INTRODUCTION: The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). METHODS: All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. RESULTS: A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to six antigen mismatches, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF does not obviate the benefits of HLA matching, while HLA matching does not minimize the benefits of MMF on long term graft survival. Our study would suggest that HLA matching and MMF therapy are additive factors in decreasing the risk for renal allograft loss.

Lack of correlation between the magnitude of preservation injury and the incidence of acute rejection, need for OKT3, and conversion to FK506 in cyclosporine-treated primary liver allograft recipients.

In order to study further whether a relationship exists between the extent of ischemia-preservation-reperfusion injury (IPRI) and acute rejection (AR) events in liver allografts, we retrospectively reviewed 213 consecutive cyclosporine-treated patients who received their first liver allograft between 1/1/93 and 12/31/93. Of these, 178 fulfilled the study inclusion criteria. The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr posttransplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax < 600 IU/L (n = 43); group 2, ASTmax 600-2000 IU/L (n = 86); and group 3, ASTmax > 2000 IU/L (n = 49). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and UNOS status as covariates. At a median follow-up of 271 days there were no statistically significant differences between groups with respect to the incidence of a first episode of AR (47%, 55%, 51%, respectively, P = NS), the timing of AR (respective medians, 9, 10, and 10 days, P = NS), or the proportion of patients treated with OKT3 (9%, 20%, 12%, respectively, P = NS) or converted to FK506 (16%, 12%, 10%, P = NS). Cox regression confirmed the lack of an independent association between the extent of IPRI and any of these outcomes. We conclude that in UW-preserved, cyclosporine-treated primary liver allografts, no correlation exists between the extent of IPRI and the incidence, timing, severity, or refractoriness of clinically defined AR events.

Selective targeting of Kupffer cells with liposomal butyrate augments portal venous transfusion-induced immunosuppression.

BACKGROUND: Enhanced Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2) has been shown to be a mechanism of the immunosuppressive effect of portal venous transfusions (PVT). Butyrate, a four-carbon short-chain fatty acid, has received increased attention because of its ability to enhance gene transcription. This study tested the hypothesis that the intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production and thus augments the immunosuppressive effect of PVT. METHODS: Butyrate was incorporated into liposomes and administered intravenously to Lewis rats. Control rats were administered liposomes without butyrate. Twenty-four hours after liposome injection, rats were administered a PVT of 1 ml of Wistar-Furth blood. Kupffer cells were isolated, and PGE2 and tumor necrosis factor-alpha levels were measured in the culture medium after 24 hr. Additionally, Kupffer cells from butyrate-treated and control animals were added to one-way mixed lymphocyte reaction cultures. RESULTS: Intrahepatic delivery of butyrate via liposomes increased Kupffer cell PGE2 (3800+/-1220 vs. 1010+/-119 pg/ml, P<0.05) and decreased tumor necrosis factor-alpha (1670+/-81 vs. 3360+/-415 pg/ml, P<0.01) production as compared with controls. Butyrate also augmented the Kupffer cell-mediated immunosuppression as demonstrated by significant depression of the mixed lymphocyte reaction (690+/-119 vs. 3850+/-148 cpm, P<0.01). CONCLUSION: The results support the hypothesis that intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production, and specific targeting of Kupffer cells with liposomes containing immunomodulating agents such as butyrate may be a useful means of augmenting immunosuppression protocols in organ transplantation.

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

Significance of early aminotransferase elevation after liver transplantation.

BACKGROUND: We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome. METHODS: The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates. RESULTS: Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI. CONCLUSIONS: We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.

Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin.

This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy-methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months = 221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506 [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6 months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients.

A prospective study on the reliability and cost effectiveness of preoperative ultrasound screening of the "marginal" liver donor.

With the growing shortage of available liver donors, many donors with risk factors that would have traditionally precluded liver procurement are now being considered. In this prospective study, we evaluated 50 "marginal" liver donors with pre-procurement abdominal ultrasounds and correlated results with findings at procurement and with subsequent allograft function. The results show that the ultrasounds have a specificity of 96% and a sensitivity of 68% in predicting abnormalities in donor livers that precluded transplantation. In addition, using ultrasound to screen marginal donors would result in significant savings in manpower and hospital resource utilization without "missing" any normal liver organs. Our results also show that, when properly selected, livers from donors with one or more high-risk factors function well with acceptable primary nonfunction rates.

Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death.

BACKGROUND: The number of patients waiting lung transplantation greatly exceeds the supply of donors. This study was conducted to determine the effect of high-dose steroid administration on oxygenation and donor lung recovery after brain death. METHODS: A retrospective analysis was conducted on 118 consecutive organ donors from January 1 through December 31, 1995. Eighty donors received high-dose steroids (methylprednisolone, mean 14.5+/-0.06 mg/kg) after organ procurement organization management began; a second group was composed of 38 patients who received no steroids. PaO2/FiO2 ratios were used to evaluate oxygenation. The number of single and double lungs transplanted served as the endpoint. RESULTS: No differences were noted in hemodynamics, most clinical or demographic variables and initial values of PaO2/FiO2 between groups. However, nonsteroid-treated donors showed an overall decrease in oxygenation (mean decrease in PaO2/FiO2 -34.2+/-14), whereas steroid-treated donors had a significant and progressive increase in oxygenation (mean increase in PaO2/FiO2: 16+/-14) before aortic cross-clamping (p = 0.01). Time before cross-clamping was longer in the steroid-treated patients (p = 0.003). The number of procured lungs was markedly greater in steroid-treated than nonsteroid-treated donors (25/80 patients vs 3/38; p < 0.01). CONCLUSIONS: High-dose methylprednisolone given during donor management results in improved oxygenation at organ recovery. This treatment resulted in a significant increase in the number of lungs transplanted and may have enabled donors to be treated longer.

Improved results of liver transplantation in patients with portal vein thrombosis.

OBJECTIVE: To analyze the impact of preexisting portal vein thrombosis (PVT) on the operative management and outcome of liver transplantation. DESIGN: Retrospective review of 1423 patients who received transplants over 11 years. SETTING: Tertiary referral center. PATIENTS OR OTHER PARTICIPANTS: Seventy patients who underwent liver transplantation who had preexisting PVT. INTERVENTIONS: Portal vein thromboendovenectomy, vein grafting, or use of portal collateral veins for inflow during liver transplantation. MAIN OUTCOME MEASURES: Postoperative PVT, intraoperative transfusion, retransplantation rate, 30-day and 1-year actuarial survival rates. RESULTS: Operative management consisted of thromboendovenectomy in 61 cases, vein graft to the superior mesenteric vein in 6 cases, and vein graft to other mesenteric veins in 3 cases. The incidence of posttransplant PVT was 3% (n = 2). The mean +/- SD transfusion requirement was 23 +/- 18 U. The 1-year actuarial survival rate was 74% but improved from 66% in the first 35 cases to 82% in the latter 35 cases. CONCLUSIONS: Thromboendovenectomy is the procedure of choice for PVT. Results of liver transplantation in patients with PVT improve significantly with experience gained and are equivalent to results in patients without PVT.

The impact of microsurgical hepatic arterial reconstruction on the outcome of liver transplantation for congenital biliary atresia.

BACKGROUND: Hepatic artery thrombosis (HAT) after liver transplantation for biliary atresia (BA) is a serious complication that most often leads to retransplantation (re-OLT). The purpose of the present study was: (1) to identify risk factors associated with HAT and (2) to analyze the impact of recently introduced microsurgical hepatic arterial reconstruction (MHR) on the incidence of HAT, subsequent need for re-OLT, and patient survival. METHODS: A retrospective review of 194 patients transplanted for BA was performed. One hundred and sixty-six patients (group 1) underwent conventional arterial reconstruction and 28 (group 2) had MHR. RESULTS: Actuarial survival for patients with HAT was significantly worse than for patients without HAT at 1, 2, and 5 years (71%, 61%, and 57% versus 85%, 85%, and 85%, P = 0.0007). Stepwise logistic regression analysis revealed that the risk of HAT correlated best with the type of arterial reconstruction (P = 0.007) followed by pretransplant bilirubin concentration (P = 0.04) and the number of acute rejection episodes (P = 0.03). In group 1, 32 patients developed HAT (19%), and of these, 18 underwent re-OLT for HAT. No patient in group 2 developed HAT (P = 0.006 versus group 1). One-year actuarial patient survival was 81% in group 1 and 100% in group 2 (P = 0.02). CONCLUSIONS: In OLT for BA, (1) the predominant risk factor for HAT is the technique of arterial reconstruction, and (2) MHR markedly reduces the incidence of HAT and the need for re-OLT while improving patient survival.

The role of whole organ pancreas transplantation in the treatment of type I diabetes.

UNLABELLED: BACKGROUND AND DEMOGRAPHICS: Clinical course was reviewed for 19 whole organ pancreas transplant recipients at UCLA between 11/14/93 and 5/31/95, 18 of which were simultaneous pancreas kidney transplants and 1 of which was an isolated pancreas after kidney transplant. The initial 4 pancreatic grafts were procured by classical warm dissection techniques while the remaining 15 were procured by rapid en bloc technique. Mean recipient age, duration of diabetes, and daily insulin requirements were 38 years, 25 years, and 45 units, respectively. Bladder drainage of exocrine secretions was used primarily in 18 cases and primary enteric drainage in one. RESULTS: All recipients manifested immediate dialysis and insulin independence. Actuarial patient and graft survival were 100% and 89%, respectively, at a mean follow-up of 396 days (range, 150-660 days). Mean maximal serum amylase on the first postoperative day was 366 U/dL. There were no instances of pancreatic graft vascular thrombosis. Three patients experienced pancreatic leaks (16%), 1 of which resulted in graft loss. Six month posttransplant Hgb A1c was within normal range and significantly lower than pretransplantation values (5.1 vs 10.7, P = 0.002). Mean length of initial hospitalization was 15 days, with 100% of patients requiring at least one read mission. Fifty-eight percent of patients experienced rejection episodes. Ninety-one percent of patients responding to a quality of life survey reported improvement in general sense of well-being after transplantation. CONCLUSIONS: It is concluded that high rates of success may be possible with whole organ pancreas transplantation, even in new programs. Rapid en bloc dissection is a safe, expeditious method of pancreas procurement. Successful pancreatic transplantation is associated with freedom from exogenous insulin administration, normalization of glycated hemoglobin, and subjective improvement in quality of life. However, this modality is associated with higher rates of rejection and readmission, and longer duration of hospitalization when compared with isolated kidney transplantation.

Orthotopic liver transplantation from a donor with a history of schistosomiasis.

The shortage of liver donors and the increasing number of patients on the waiting list for liver transplantation have led to a widening of the definition of suitable liver donors. In this case report, we describe transplantation of a liver from a 20-year-old brain-dead donor with a past history of schistosomiasis. Careful evaluation for schistosomiasis-related hepatic complications using hepatic function tests, clinical assessment for manifestations of portal hypertension, as well as abdominal ultrasound, and liver biopsy were performed. At 7 months follow-up, the recipient is doing well with normal liver function. Liver transplantation from a donor with a history of schistosomiasis is acceptable in carefully screened cases.