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M S Cattral

Publications and source records attributed to M S Cattral.

At least 37 records · Page 2Linked to original sources
PubMed1998

Donor-specific stimulation of peripheral blood mononuclear cells from recipients of orthotopic liver transplants is associated, in the absence of rejection, with type-2 cytokine production.

In this study, we examined the cytokine production by human peripheral blood mononuclear cells (PBM) from recipients of orthotopic liver transplants which had been stimulated by donor-specific alloantigen. Levels of interleukin (IL)-2, IL-4, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta produced in vitro from PBM of 15 transplant recipients at 5-7 months post transplantation were analysed after donor-specific, third-party, or non-specific stimulation. Mononuclear cell proliferation in response to stimulation and cytokine mRNA from the cell cultures were assayed. Donor-specific antigen was obtained from donor spleen cells which had been obtained and frozen in liquid nitrogen at the time of organ retrieval. Third-party restimulation used equivalent numbers of spleen cells pooled from the other 14 organ donors. Cytokine production was correlated with the clinical condition of the patient, including biopsy results when available, and biochemical data. The data show a highly significant correlation between the donor-specific- and third-party- stimulated IL-4 and IL-10 production from recipient PBM with stable liver graft function as assessed by histopathology and/or biochemistry. This correlation was independent of level of immunosuppression. These data strongly support a role for IL-4 and/or IL-10 in the induction and/or maintenance of tolerance to human liver allografts. Measurement of the levels of these cytokines from recipient PBM after donor-specific antigen stimulation in vitro may be a useful test for monitoring for acute allograft rejection.

Adjuvants, Immunologic↗
PubMed1998

A pharmacoeconomic analysis of Neoral without intravenous cyclosporine in liver transplantation in Canada.

Neoral, a microemulsion formulation of cyclosporin A (CsA), has improved absorption compared to Sandimmune and has allowed induction of immunosuppression in liver transplantation (LT) without the use of intravenous (i.v.) CsA. The improved bioavailability with less inter- and intra-patient dosing variability coupled with the lack of requirement for i.v. CsA may provide a mechanism for cost savings when Neoral is used for induction immunosuppression. This retrospective case-control study compares the relative costs associated with Neoral induction without i.v. CsA versus induction with i.v. CsA followed by oral CsA in adult liver transplant recipients. Twenty consecutive patients receiving Neoral 12-15 mg/kg per d were compared to a control group of 21 patients receiving i.v. CsA followed by oral CsA for induction. Both groups received the same rapidly tapered dose of methyl-prednisilone. Health care resource utilization was assigned based on days in hospital and acute rejection episodes (ARE). Hospital per diem rates at specified care levels were used to assign costs associated with hospital stay, while a previously developed case-costing model was used to assign costs to episodes of acute rejection. All patients were followed for a 3-month period post-transplant. Although there was a trend towards shorter hospital stay in the Neoral group the majority of cost savings were achieved by reducing costs associated with episodes of acute rejection. There were seven and 19 episodes of ARE in the Neoral and i.v. CsA groups respectively (p < 0.05.) A separate cost effective assessment of the effect of reducing rejection by decision tree analysis demonstrated a cost reduction of $2162 per patient. The savings achieved with Neoral proved robust on sensitivity analysis. The change of practice to an induction immunosuppression regimen of Neoral without i.v. CsA has achieved a cost savings in adult liver transplantation at our center.

Adult↗
PubMed1997

Evaluation of liver transplantation for high-risk indications.

BACKGROUND: Appropriate use of orthotopic liver transplantation (OLT) requires continued assessment of the indications for transplantation as a number of diseases are associated with a poor prognosis. High-risk patients are those who have a poor survival or high incidence of recurrent disease (patients with tumours, hepatitis B- or hepatitis C-induced cirrhosis, fulminant hepatic failure or primary graft non-function). In addition, retransplantation may be associated with a poor outcome. METHODS: A retrospective review was made of the records of all adult patients undergoing OLT at this hospital between October 1985 and July 1994. RESULTS: A total of 396 liver transplants were performed in 364 patients. The 1- and 3-year actuarial survival rates were 81 and 69 per cent respectively. The overall survival rate of high-risk patients was significantly lower than that for all OLT recipients (P < 0.05). While no patients transplanted for hepatitis C have developed graft failure, recurrent hepatitis occurred in 15 of 35 patients. CONCLUSION: Strict selection criteria and appropriate perioperative investigations and interventions are required to improve the results of OLT in these high-risk patients.

Adolescent↗
PubMed1996

A microemulsion of cyclosporine without intravenous cyclosporine in liver transplantation.

A microemulsion formulation of cyclosporine (CsA) has improved absorption compared with the original form. The purpose of this case control study was to assess the safety and efficacy of the microemulsion without intravenous CsA for induction immunosuppression in adult liver transplantation. Twenty-one consecutive patients receiving induction immunosuppression with the microemulsion 15 mg/kg/day were compared with 20 patients receiving intravenous CsA and the original oral form. Both groups received the same dose of methylprednisilone. Twenty of 21 patients receiving the microemulsion required no intravenous CsA to achieve target CsA levels. All patients receiving the original form received initial intravenous CsA. There was no difference in trough CsA levels between the two groups at 24 and 48 hours. The microemulsion group had 24 hr and 48 hr trough CsA levels of 227+/-15 and 520+/-300 ng/ml by monoclonal RIA while the intravenous CsA group had 24 and 48 hr trough levels of 293+/-18 and 405+/-91 ng/ml. CsA levels analyzed by HPLC were 20% lower than by RIA. The frequency of adverse events resulting in reduction of drug dosage was similar for the microemulsion and the original form: neurotoxicity (23 vs. 40%, P=.30); nephrotoxicity (25 vs. 45%, P=.32), and no patients required dialysis. There was no difference in septic complications. One patient required discontinuation of the microemulsion in an attempt to reverse severe neurotoxicity. A total of 75% of microemulsion patients were rejection free at 3 months while only 35% of CsA patients remained rejection free (P=0.02). These data suggest that the use of the microemulsion without intravenous CsA in liver transplantation is safe and efficacious, and may result in decreased episodes of acute rejection.

Adult↗
PubMed1996

A pilot study of ribavirin therapy for recurrent hepatitis C virus infection after liver transplantation.

Ribavirin is a guanosine analogue that normalizes serum liver enzymes in most nontransplant patients with chronic hepatitis C virus (HCV) infection. We conducted an uncontrolled pilot study of ribavirin in 9 liver transplantation recipients that had persistently elevated liver enzymes, active hepatitis by liver biopsy, and HCV RNA in serum by polymerase chain reaction. Ribavirin was given orally at dosages of 800-1200 mg per day for 3 mo. All 9 patients promptly responded to ribavirin: mean (+/- SD) ALT decreased from 392 +/- 377 IU/L immediately before treatment to 199 +/- 185 and 68 +/- 37 IU/L after 1 and 12 weeks of treatment, respectively, complete normalization of enzymes occurred in 4 patients. None of the patients cleared the virus from their serum during therapy, and biochemical relapse occurred in all patients 4 +/- 4.2 weeks after cessation of therapy. The hepatitis activity index of liver biopsy specimens obtained before and at the cessation of therapy was similar. Ribavirin treatment was resumed in 4 patients because of increasing fatigue (2 patients), rising bilirubin (3), or increasing necroinflammation on liver biopsy (2); the biochemical response to the second course of therapy was similar to the first course in all 4 patients. Ribavirin caused reversible hemolysis in all patients, including symptomatic anemia in 3 patients that resolved after reduction of drug dosage. These results suggest that ribavirin may be of benefit in the treatment of HCV infection after liver transplantation. Further studies are needed to determine the optimal dosage and duration of therapy.

Adult↗
PubMed1996

The University of Toronto liver transplant program.

The University of Toronto liver transplant program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers which impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Our group has had a special interest in transplantation for viral hepatitis. We demonstrated the role of HBV DNA as a prospective factor in both viral recurrence and survival. We further studied a number of agents to prevent re-infection including PGE, HBIG and more recently lamivudine. Although the short-term results of transplantation for HCV appear excellent, reinfection of the graft and development of chronic hepatitis and cirrhosis may make long-term results problematic. Therefore, we have directed attention to studies of pathogenesis and treatment of HCV in liver transplantation. Our studies have demonstrated a unique role for ribavirin as an immunomodulatory agent which can benefit the course of posttransplant HCV. Future studies will examine combination therapy in an attempt to eradicate the virus. Our group also has been interested in PNF and FHF and have demonstrated a positive effect of PGE in this setting. As we look to the future, the greatest challenges facing transplantation are the shortage of organ donors and the toxic effects of long-term immunosuppression. Our group now has established research efforts both in tolerance induction and xenotransplantation which we feel are necessary to make transplantation an effective, universal treatment for end stage organ failure.

Adult↗
PubMed1995

Parvovirus B19 as a possible causative agent of fulminant liver failure and associated aplastic anemia.

We recently observed that more than one third of pediatric patients who presented with non-A, non-B fulminant liver failure (FLF) also developed aplastic anemia (AA) either before or shortly after liver transplantation. Factors involved in the suppression of bone marrow could be the same as those causing hepatic failure. We considered parvovirus B19 a candidate etiologic agent because of the known tropism of B19 for erythroid precursors. Archived liver and serum from six patients undergoing liver transplantation for non-A, non-B, non-C FLF with associated AA were analyzed for the presence of B19 DNA and anti-B19 serology. An age- and gender-matched control group (N = 44) was analyzed in parallel. B19 DNA studies and anti-B19 serology were performed in a blinded fashion. B19 serologies were performed by antibody capture enzyme-linked immunosorbent assay (ELISA). B19 DNA was detected after polymerase chain reaction (PCR) amplification of target B19 DNA sequences in liver and serum. Liver tissue showed evidence of B19 DNA in four of six (66%) patients with FLF and associated AA. Two of 4 patients with cryptogenic FLF but without AA had B19 DNA detected in the liver tissue. Of the 34 remaining controls, only 5 (15%) showed evidence of B19 DNA in liver tissue (66% vs. 15%, P = .016). B19 DNA was not detected in any of the test or control sera. This study provides evidence to support the role of parvovirus B19 in the development of FLF and associated AA.

Anemia, Aplastic↗
PubMed1994

Transfusion-induced graft-versus-host disease after liver transplantation. Documentation using polymerase chain reaction with HLA-DR sequence-specific primers.

Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.

Biopsy↗
PubMed1994

Viral prophylaxis in combined pancreas-kidney transplant recipients.

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

Adult↗
PubMed1994

Aplastic anemia after liver transplantation for fulminant liver failure.

We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non-A, non-B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or infection with hepatitis C virus (as determined with a second-generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)--one at 43, one at 108 and one at 119 days after transplantation--without remission of aplastic anemia. Among the four surviving patients, with median follow-up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non-A, non-B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery.

Adolescent↗
PubMed1994

Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease.

BACKGROUND: Prostaglandins are cytoprotective agents that have been shown to benefit patients with a variety of acute and chronic liver diseases. Few data exist on the frequency of adverse effects of prostaglandins in these patients. METHODS: We retrospectively studied 105 patients with liver disease who were treated with either intravenous (i.v.) or oral prostaglandin E (PGE). Forty-four patients with primary nonfunction after liver transplantation and 36 patients with fulminant hepatic failure received i.v. PGE1 for 4.5 +/- 2.6 and 12.6 +/- 10.9 days, respectively. Twenty-five patients with recurrent hepatitis B viral infection after liver transplantation received oral PGE1 for 105 +/- 94 days or PGE2 for 464 +/- 399 days. RESULTS: Twenty-six of 80 patients (33%) receiving i.v. PGE1 developed gastrointestinal and/or cardiovascular side effects and 8% developed arthritis. Twenty-three of 25 patients (92%) who received high-dose oral PGE1 or PGE2 incurred arthritis and/or gastrointestinal adverse effects. Twenty-five patients received prolonged PGE therapy (oral > 60 days; i.v. > 28 days). Of this group, 23 (92%) developed clubbing and cortical hyperostosis resembling hypertrophic osteoarthropathy. All adverse effects were dose related and resolved with reduction or cessation of therapy. CONCLUSION: PGE therapy resulted in a wide spectrum of multisystem adverse effects which were reversible with reduction or cessation of therapy. Although the administration of PGE was safe and generally well tolerated, close medical supervision is necessary to avoid serious side effects.

Administration, Oral↗
PubMed1994

Improved survival of in vitro cultured canine islet allografts.

Pure islets transplanted from single donors survive in outbred dogs when CsA is administered at high doses (15-20 mg/kg/day), but not report has documented prolonged function with less CsA. In this study, we investigated survival of canine islets that were immunomodulated with in vitro culture and transplanted with minimal CsA. Highly purified islets from single donors (n = 17) were cultured in vitro at 22 degrees C for 7 days. Four groups of apancreatic, outbred mongrel dogs received islets into the spleen: group 1 (n = 4), fresh islet controls; group 2 (n = 5), cultured islet controls; group 3 (9033 +/- 994 islets/kg, n = 12), culture and CsA; group 4 (9050 +/- 1091 islets/kg, n = 8), fresh islet and CsA. CsA was administered in doses of 5-8 mg/kg/day to maintain whole blood trough levels of 300-500 ng/ml. At 30 days after implant, the CsA was stopped. After 7-day culture, 80% of the endocrine mass was recovered. All grafts restored plasma glucose to < 150 mg/dl. Group 1 and 2 dogs became hyperglycemic at 5 +/- 1 (+/- SE) and 6 +/- 1 days. Three grafts in group 3 failed when CsA did not reach target blood levels. Of the 9 dogs with CsA levels of 300-500 ng/ml, 1 died at 9 days while normoglycemic, and the remainder were normoglycemic for 35.5 +/- 8.3 days (median 38 days). Seven group 4 dogs with these CsA levels achieved normoglycemia for 7.7 +/- 1.9 days (median 9 days, survival vs. group 3, P = 0.03, by Mann-Whitney test). In vitro tissue culture of mass quantities of single-donor allogeneic islets enhances their survival with low dose immunosuppression in outbred diabetic dogs.

Animals↗