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B Nashan

Publications and source records attributed to B Nashan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Background and prognostic implications of perireperfusion tissue injuries in human liver transplants: a panel histochemical study.

BACKGROUND: Hepatic graft reperfusion is associated with inflammatory processes of unknown relevance to the fate of graft. This study aimed to clarify this relevance by histochemical analyses of human hepatic grafts. METHODS: Paired tissue samples were taken at the end of cold preservation and 2 hr after reperfusion (n=39). From six additional grafts, biopsies were performed at the end of cold preservation only. Injury or inflammatory markers of sinusoidal endothelium (von Willebrand factor-related antigen [vWF]), Kupffer cells (25F9), platelets (CD62), neutrophil leukocytes (CD11b), interleukin (IL)-1beta, intercellular adhesion molecule (ICAM)-1, and HLA-DR were evaluated semiquantitatively by indirect immunoperoxidase staining. Steatosis was also evaluated by hematoxylin and eosin staining. RESULTS: vWF, CD62+ platelet aggregation, CD11b+ leukocytes, and IL-1beta levels increased after reperfusion, and these levels correlated with prereperfusion levels. Not only vWF, CD62+ platelets, CD11b+ leukocytes, IL-1beta, ICAM-1, and steatosis after reperfusion, but also IL-1beta, ICAM-1, and steatosis before reperfusion correlated with postoperative peak transaminase. Furthermore, vWF, CD11b+ leukocytes, 25F9+ macrophages, and ICAM-1 after reperfusion were associated with primary graft nonfunction and strong expressions of ICAM-1 or HLA-DR with early acute rejection. Although some markers (IL-1beta, CD62+ platelets, and CD11b+ leukocytes) correlated with preharvesting parameters (donor age or length of intensive care unit stay), none showed any significant correlation with cold preservation. CONCLUSION: Synergistic inflammatory events in the hepatic graft at reperfusion, which have a significant impact on the later clinical course, are largely defined and precipitated by injury or activation of nonparenchymal cells preceding reperfusion or even graft harvesting.

Adolescent↗
PubMed1998

Antibodies against the GB virus C envelope 2 protein before liver transplantation protect against GB virus C de novo infection.

GB virus C (GBV-C) is a newly discovered RNA virus related to the Flaviviridae family. Although GBV-C is not yet associated with any cause of liver disease, a humoral immune response against the GBV-C envelope 2 (E2) protein has been observed. Therefore, we studied the prevalence and clinical relevance of GBV-C RNA and anti-E2 antibodies in patients undergoing orthotopic liver transplantation (OLT). In addition, we tested whether the prevalence of anti-E2 antibodies may protect against GBV-C infection. Of the 182 liver recipients included in this study, 117 of these were evaluated for GBV-C recurrence or de novo infection. GBV-C RNA was detected in sera or plasma using single-tube, reverse-transcriptase polymerase chain reaction, and anti-E2 antibody was detected by enzyme immunoassay (EIA). Cumulative patient and graft survival was tested by using Kaplan-Meier analysis. The independence of prognostic values was assessed by using Cox regression analysis. Before OLT, GBV-C RNA and anti-E2 were detected in 4.0% to 28.6% and 10.0% to 68.8%, respectively, of patients suffering from different forms of chronic liver diseases. GBV-C reinfection after OLT was determined in 85.7%. Of the patients without evidence of exposure to GBV-C before OLT, 30 of 65 (46.2%) became GBV-C RNA positive after OLT. None of the 38 patients who were anti-E2 antibody positive before OLT became GBV-C RNA positive after OLT. Neither patient nor graft survival was significantly affected by the presence of either GBV-C RNA or anti-E2 antibody before OLT. Our data indicate that 1) GBV-C RNA positive patients have a high risk of reinfection after OLT, and 2) the presence of anti-E2 antibodies before OLT is associated with an absence of GBV-C infection after OLT, which may indicate a protective role of anti-E2 antibodies.

Adult↗
PubMed1998

Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas positive for inhibin. A hint concerning its possible histogenesis.

A female patient with a mucinous cystadenocarcinoma originating from a mucinous cystadenoma of the pancreas is presented. The cystic tumour was diagnosed 3 years before and was treated with interventional external and internal surgical drainage before radical resection was accomplished by left hemipancreatectomy. Histology showed simultaneous occurrence of mildly dysplastic and invasive malignant epithelium. Immunohistology revealed inhibin-positive cells in the ovarianlike stroma of the tumour. The demonstration of ovarian-like stroma positive for inhibin suggests that this could be a hamartoma with dispersed sex-cord stroma, which would explain the predominance of the female gender in mucinous cystic tumours of the pancreas.

Adult↗
PubMed1998

Disposition and immunodynamics of basiliximab in liver allograft recipients.

A randomized, open-label prospective study was conducted with recipients of primary cadaveric liver allografts to characterize the disposition and immunodynamics of basiliximab, an interleukin-2 receptor, alpha-chain chimeric monoclonal antibody for immunoprophylaxis of acute rejection. Patients received a total intravenous dose of 40 mg basiliximab in addition to baseline dual immunosuppression consisting of cyclosporine (INN, ciclosporin) and steroids. The central distribution volume was 5.6 +/- 1.7 L with a steady-state volume of 7.5 +/- 2.5 L. It was cleared slowly with a total body clearance of 75 +/- 24 ml/hr and an elimination half-life of 4.1 +/- 2.1 days. Basiliximab was measurable in drained ascites fluid, and clearance by this route was an average of 20% of total clearance. Total body clearance correlated positively with volume of postoperative blood loss (r = 0.5253, p = 0.0101), suggesting that bleeding may represent an additional route of drug removal. A threshold relation was observed between serum concentration of basiliximab and CD25 expression on T lymphocytes whereby complete saturation of interleukin-2 receptor alpha-chain was maintained as long as serum concentrations exceeded 0.1 microgram/ml. The duration of receptor saturation was 23 +/- 7 days after transplantation (range, 13 to 41 days).

Adolescent↗
PubMed1998

Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?

BACKGROUND/AIMS: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

Carcinoma, Hepatocellular↗
PubMed1998

[De novo hepatitis B infection after liver transplantation--evidence for the need of active hepatitis B vaccination of liver transplantation candidates].

BACKGROUND: Liver transplantation (LTX) is a generally accepted therapy in the treatment of acute and chronic end-stage liver diseases. Recurrent and de-novo hepatitis B and C virus infection following liver transplantation have been shown. PATIENTS AND METHODS: We analyzed retrospectively the course of patients treated at our transplant center between 01.01.1992 and 31.12.1997, who does not show any markers of an active hepatitis B (HBV) infection prior to liver transplantation but developed replicative HBV infection afterwards. During this period 544 liver transplantations were performed in 452 patients, 395 of whom were HBs-Ag negative prior to transplantation. RESULTS: Six patients were identified who underwent LTX for non-hepatitis B-induced liver disease, and who subsequently developed a highly replicative de-novo HBV-infection six to twelve months (mean 8.5 months) after LTX. In each of the patients HBV de-novo infection showed clinically and biochemically a mild but chronic course without evidence of liver failure during a maximum follow-up period of 14 to 37 months (mean 26 months). Liver biopsies taken in four patients nine to 22 months after LTX showed chronic active hepatitis (n = 2), chronic portal hepatitis (n = 1), and a mild rejection (n = 1). The source of de-novo HBV infections remained unclear, but inapparent infection of patients pre-LTX was ruled out so that the donor livers or postoperative infection appear to be the likely source. CONCLUSION: In our center the number of HBV de-novo infections (1.5%, 6/395) following liver transplantation was comparable to the results published by other centers, but in our center no inapparent infection of patients prior to LTX was observed. For further minimization of HBV de-novo infection following LTX active HBV immunization of patients awaiting LTX is recommended.

Adult↗
PubMed1998

Metastatic pancreatic VIPoma: deteriorating clinical course and successful treatment by liver transplantation.

Gastrointestinal neuroendocrine tumors are slowly growing and metastases are often limited to the liver. As a result of their favorable biological behavior these tumors have a relatively good prognosis even in metastatic stage. Due to a variety of therapeutic options patients with malignant neuroendocrine tumors may survive for extended periods of time up to ten years. Often a combination of different treatments and also alternation between the different therapeutic regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic disturbances due to a pancreatic VIPoma with metastatic spread into the liver and abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5-fluorouracil and adriamycin) were able to alleviate clinical symptoms and to control tumor growth for six years. Analogues of somatostatin (octreotide) and interferon alpha had been very useful in controlling clinical symptoms and tumor progress for 18 months. Cytotoxic agents or octreotide were not able, however, to achieve any permanent cure. Eventually, treatment failure occurred with dramatic progression of symptoms and tumor growth, unresponsive to any medical therapy. Consequently, total hepatectomy and liver transplantation together with extirpation of the pancreatic primary tumor was performed and succeeded in providing a normal life to the patient. In our opinion the overall outcome of patients with metastatic VIPoma may be improved best by maintaining the patients on medical therapy until treatment failure occurs. In case of extended hepatic metastases orthotopic liver transplantation might be considered for patients with symptomatic disease who no longer respond to conventional treatment modalities.

Chemotherapy, Adjuvant↗
PubMed1998

Outcome of 22 successful pregnancies after liver transplantation.

To evaluate course and outcome of pregnancies in liver transplanted patients and to provide a brief summary on the development of these children, 22 pregnancies and 23 children (1 month-99 months old) of 16 patients who had been liver transplanted at our institution (mean interval from transplantation to pregnancy 43.1 months) were reviewed. Standard immunosuppressive regimen during pregnancy consisted of cyclosporine A (CyA), tacrolimus (FK), azathioprine (Aza) and/or a low-dose steroid therapy. CyA and FK whole blood trough levels were monitored on a routinely basis to keep therapeutic range (CyA 80-150 ng/mL; FK 4-8 ng/mL). No patient had a graft loss and there were no lethal complications. Beside de novo hypertension (n = 3) and preeclampsia (n = 3) problems during pregnancy included one steroid-sensitive rejection at 36 wk gestation, one case of tacrolimus toxicity at 24 wk with complete reconstitution, and one case of de novo choledocholithiasis with recurrent cholangitis. Three cases of infections occurred. In total, 23 children, including one set of twins, were born. Terms of gestation (mean = 38.1 wk, +/- 2.2 SD), deliveries (spontaneous n = 13, cesarean section n = 7, forceps n = 1, vacuum extraction (VE) n = 1) and birth weights (2876 g, +/- 589.3 SD) were typical. Three pregnancies were preterm, one being a twin pregnancy. Neither congenital malformations nor unusual infections were seen in the children. Postnatal follow-up revealed appropriate physical growth to date. Psychological development seems to be adequate. Our data indicate that successful pregnancies after liver transplantation (LTX) under careful management by transplant specialists, obstetricians and perinatalogists have a good outcome. So far, neither pre- nor postnatal child development appear to be influenced by maternal immunosuppressive therapy during pregnancy.

Adult↗
PubMed1997

Recurrent immunoglobulin A nephropathy after renal transplantation: a significant contributor to graft loss.

BACKGROUND: Although most transplanted patients with underlying IgA nephropathy (IgAN) develop histological recurrence, its clinical relevance is considered low. METHODS: We performed a single-center analysis of 61 renal transplant patients with IgAN. RESULTS: Forty-four percent of the patients showed a stable graft function. Progressive graft dysfunction apparently due to recurrent IgAN occurred in 23% of the patients (16% required dialysis). Five patients were retransplanted, and three again developed dialysis-dependent renal failure apparently due to recurrent IgAN. In 20% of the patients, chronic transplant dysfunction was due to other reasons, whereas no reason was identified in 13% of the patients. Neither findings before transplantation, the ACE genotype, the type of immunosuppression, nor the course after transplantation predicted transplant dysfunction due to recurrent IgAN. Follow-up after transplantation was longer in the group with dysfunction due to recurrent disease than in the group with dysfunction due to chronic rejection or in the stable group. CONCLUSION: Recurrent IgAN is a clinically relevant problem in renal transplant patients. Its importance may have been underestimated in the past due to inadequate lengths of follow-up.

Adult↗
PubMed1997

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.

Acute Disease↗
PubMed1997

Renal transplantation for patients with autoimmune diseases: single-center experience with 42 patients.

BACKGROUND: In patients with autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE), end-stage renal disease develops in a high percentage of patients, and kidney transplantation has become a therapeutic option. However, only limited data about the prognosis and outcome after kidney transplantation are available. METHODS: Long-term graft survival and graft function of renal transplant recipients with SLE, Wegener's granulomatosis, microscopic polyangiitis, Goodpasture's syndrome, and Henoch-Schonlein purpura were evaluated in a single center. In addition, the incidence of renal and extrarenal relapses and the impact of the immunosuppressive therapy on the course of the autoimmune disease were studied. RESULTS: Renal transplant recipients with autoimmune diseases such as vasculitis and SLE had a patient survival rate (94% after 5 years) and a graft survival rate (65% after 5 years) comparable to those of patients with other causes of end-stage renal disease (patient survival 88% and graft survival 71% after 5 years). Graft losses due to the underlying disease were rare. Extrarenal relapses occurred in three patients with Wegener's granulomatosis, one patient with microscopic polyangiitis, and three patients with SLE, but were less frequent compared with the period with chronic dialysis therapy. Autoantibody levels in patients with SLE, Wegener's granulomatosis, or microscopic polyangiitis did not seem to influence the outcome. CONCLUSIONS: Renal transplantation should be offered to patients with autoimmune diseases. Follow-up should include the short-term control of renal and extrarenal disease activity.

Adult↗
PubMed1996

Fibrosis in chronic rejection of human liver allografts: expression patterns of transforming growth factor-TGFbeta1 and TGF-beta3.

Activation and transformation of lipocytes (Ito cells, stellate cells) into alpha-actin-positive myofibroblast-like cells is an essential step in the initiation of liver fibrosis. Transforming growth factor-beta (TGF-beta) is considered an important mediator of this process. In order to determine mechanisms of fibrotic deposition in a hepatic transplant setting, we analyzed 10 chronically rejected human liver allografts for the expression of extracellular matrix (ECM) molecules, myofibroblast-like cells (alpha-actin), macrophages, and TGF-beta1 and -beta3. Using single- and double-immunohistochemical staining techniques, all specimens investigated showed increased deposition of the ECM proteins fibronectin, tenascin, undulin, and collagen VI with a characteristic densification especially in pericentral areas. Likewise, strong accumulation of alpha-actin-positive cells and TGF-beta1-expressing macrophages was observed in the same fields, supporting the concept of lipocyte activation/transformation and subsequent ECM production fostered by macrophage-derived TGF-beta1. In contrast, TGF-beta3 was found to be mainly expressed by a markedly increased number of lipocytes. Interestingly, distribution of TGF-beta3 corresponded to that of tenascin, an ECM molecule known to be involved in early matrix organization, suggesting that TGF-beta3 may likewise act mainly in early stages of fibrogenesis. Furthermore, TGF-beta3 restriction to high numbers of a single cell type (i.e., lipocytes) implied a possible role in cell proliferation through autocrine loops. In conclusion, fibrosis in chronic rejection seems to follow similar mechanisms as in non-transplanted livers but additionally suggests differential temporal and functional roles for the TGF-beta isoforms 1 and 3 in the course of a multistep process leading to lipocyte transformation and ECM production.

Actins↗
PubMed1996

Immunoprophylaxis with a monoclonal anti-IL-2 receptor antibody in liver transplant patients.

The immunosuppressive effect of a monoclonal antibody (moAb), BT563, directed to the alpha-chain of the IL-2R (CD25), was analyzed in a prospective nonrandomized trial and a prospective randomized trial. Primary objectives were evaluation of the incidence of acute rejections and infections; secondary objectives were safety and tolerability of the moAb. A total of 28 patients were enrolled (phase II) to receive 10 mg/day of BT563 (12 days) as immunoprophylaxis in combination with cyclosporine, azathioprine, and low-dose steroids. Subsequently 32 patients were randomly assigned (phase III) to receive BT563 (10 mg/day) for 12 days or ATG (5 mg/kg/day) for 7 days in addition to cyclosporine and low-dose steroids. No side effects of the BT563 treatment were noted. The actuarial survival was 82% at 12 months in the phase II trial and 92% at 12 months in both arms of the phase III trial. There was one acute rejection in the phase II trial. No acute rejections were noted in the BT arm of the phase III trial and 5 acute rejections were treated in the ATG arm. In the phase II trial 7 infectious episodes were observed, while one infection was seen in the BT arm and 7 in the ATG arm of the triple immunosuppression phase III trial. In all patients circulation of coated CD25+ lymphocytes was observed during BT563 treatment; there was no evidence of depletion or modulation of CD25+ cells. Mean serum levels of BT563 ranged from 1.6 to 7.6 microgram/ml throughout the therapy. An antimurine response was seen in 82% (phase II) and 100% (phase III) of the patients. Antirabbit antibodies were found in 56% of the patients treated with ATG. Analysis of the antimurine response specificity revealed in 56% blocking anti-isotypic antibodies and only in 3% of the patients an anti-idiotypic response. The data of the study presented suggest that therapy with an anti IL-2R moAb is at least equal to ATG application according to the incidence of acute rejections and infections.

Acute Disease↗
PubMed1996

Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease associated in 10% to 36% of those with hepatobiliary malignancies, which are, in the majority of cases, not known prior to transplantation. Diagnosis of carcinomas in a PSC setting at an early stage has not yet been achieved, because there are no differences in the age of patients or clinical course, particularly with regard to the time between diagnosis of PSC and detection of carcinomas. To assess optimal timing for transplantation in patients with PSC, we applied the Mayo survival model to 48 patients receiving transplants for that disease in our center between 1972 and 1994. Of these patients, 10 had a biliary malignancy, which was incidental in 9. According to the Mayo model, low-, moderate-, and high-risk groups of patients could be formed. The actuarial patient survivals at 1 and 7 years were 100% and 100% (low risk), 68.6% and 68.6% (moderate risk), and 54.6% and 46.8% (high risk), respectively. Patients with a biliary malignancy had a 30% survival at 1 year; none survived 6 years. Local recurrence of the tumor was found in 3 patients, 2 of them with low tumor stages at the time of transplantation. Analysis of the Mayo Model risk scores demonstrated a marked increase in the incidence of biliary malignancies at a score above 4.4. All patients with tumors were found to have a score above 4. Moreover, the prevalence rate rose from 14.3% in the low-risk group to 33.3% in the moderate-risk group. There was no difference in the clinical courses at 6 to 12 months prior to transplantation; in particular, the bilirubin levels (PSC alone, 250 +/- 230 mumol/L; PSC with carcinoma, 288 +/- 182 mumol/L) did not differ significantly (P > .05) between both patient groups. Because the outcome after transplantation is poor even in patients with low-grade malignancies, early timing of transplantation in patients with PSC is suggested to prevent formation of biliary malignancies. Therefore, regular scoring of patients with the Mayo Model risk score is suggested, and transplantation should be taken into consideration at scores above 4.

Actuarial Analysis↗