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Biomedical subjects

R H Wiesner

Publications and source records attributed to R H Wiesner.

At least 163 records · Page 9Linked to original sources
PubMed1994

Soluble T lymphocyte markers in the diagnosis of cellular rejection and cytomegalovirus hepatitis in liver transplant recipients.

Hepatic dysfunction following liver transplantation is often caused by cellular rejection or infection with cytomegalovirus. These etiologies can at times be difficult to differentiate. We measured the levels of soluble T lymphocyte markers sIL2R, sCD4, and sCD8 in serum as possible diagnostic indicators of cellular rejection and cytomegalovirus hepatitis. Pretransplant levels, and serial post-transplant levels of soluble T lymphocyte markers were measured in five control patients without cellular rejection or cytomegalovirus infection, ten patients with cellular rejection, and six patients with cytomegalovirus hepatitis. In all cases, cellular rejection and cytomegalovirus hepatitis were documented with liver histology. For each group of patients, we calculated the mean ratio of the post-transplant marker level divided by the pre-transplant level. We found an elevation in the mean ratio of sIL2R in patients with cellular rejection shortly before or at the time of diagnosis of rejection as compared to the transplant control group. Levels of sCD8 were not significantly increased in patients with cellular rejection. We found a more pronounced elevation in the mean marker ratios of both sIL2R and sCD8 in patients with cytomegalovirus hepatitis which were higher compared not only to the transplant control group but also compared to the cellular rejection group. The rise of serum levels preceded the histologic diagnosis of cytomegalovirus hepatitis and detection of cytomegalovirus in blood cultures. Increased serum levels of sIL2R with concomitant elevation of sCD8 suggest the diagnosis of cytomegalovirus hepatitis over cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1994

Detection of cytomegalovirus DNA in sera of liver transplant recipients.

We prospectively studied the utility of the amplification of cytomegalovirus (CMV) DNA in the sera of liver transplant recipients in order to predict symptomatic CMV infection, thus enabling preemptive therapy with antiviral agents. Serum samples obtained at biweekly intervals from 20 sequential liver transplant recipients for at least 8 weeks following transplantation were tested by the PCR amplification procedure. Results were correlated with blood and urine cultures, histopathological findings from infected organs, and clinical manifestations. Six patients (30%) developed symptomatic CMV infection; in five (83%) of these patients, CMV DNA was detected prior to symptomatic CMV infection, and in one (17%) of these patients, CMV DNA was detected at the time of symptomatic CMV infection. CMV DNA was detected a mean of 13 days (range, 0 to 23 days) prior to the onset of symptomatic CMV infection. In addition, CMV DNA was detected in the sera of four of five patients with asymptomatic viremia and two patients with asymptomatic viruria. Lastly, the PCR was negative for sera from seven patients with no evidence of CMV infection. We found that PCR was able to detect the presence of CMV DNA in the sera of liver transplant recipients at a sensitivity of 92% and a specificity of 100% for CMV infection, while the sensitivity and specificity for symptomatic infection were 100 and 57%, respectively.

Base Sequence↗
PubMed1994

Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary biliary cirrhosis: applications of a semiautomated assay.

Sera from patients with primary biliary cirrhosis inhibit the activity of the mitochondrial pyruvate dehydrogenase complex. We utilized this effect to develop a simple, miniaturized, semiautomated spectrophotometric assay as a diagnostic aid. The sera studied were from 71 patients with primary biliary cirrhosis and 62 other subjects. The assays included enzyme inhibition, immunofluorescence on HEp-2 cells, enzyme-linked immunosorbent assay using recombinant pyruvate dehydrogenase complex-E2 and immunoblotting on bovine heart mitochondria. With the 71 primary biliary cirrhosis sera, on which M2 antibody was detected by immunofluorescence in 64 (90%), antibodies against pyruvate dehydrogenase complex were detected in 53 (83%) by means of enzyme inhibition, in 57 (89%) by means of enzyme-linked immunosorbent assay and in 60 (94%) by means of immunoblotting. Of the 64 sera positive by immunofluorescence, 60 reacted with pyruvate dehydrogenase complex-E2 on immunoblotting, and the miniaturized enzyme inhibition assay was positive in 53 of these. The enzyme inhibition assay and enzyme-linked immunosorbent assay were calibrated to give a specificity of 100%. At this level, the sensitivities for detection of pyruvate dehydrogenase complex antibody were 83% and 87%, respectively. We found no significant changes in levels of reactivity with the enzyme inhibition assay or enzyme-linked immunosorbent assay according to disease stage. Treatment with cyclosporine was accompanied by a significant decrease in levels of antibody to pyruvate dehydrogenase complex-E2 that matched improved indexes of biochemical liver function.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1994

Advances in diagnosis, prevention, and management of hepatic allograft rejection.

Despite recent improvements in immunosuppressive therapy, hepatic allograft rejection remains a major cause of morbidity and late graft loss in patients undergoing liver transplantation. Although some biochemical tests suggest hepatic allograft damage, the gold standard for defining rejection remains based on morphologic findings. Acute cellular rejection usually occurs within the first 3 weeks posttransplantation and the incidence varies between 40% and 70%. Ductopenic rejection occurs in 5-10% of patients undergoing initial liver transplantation and usually occurs between 6 weeks and 6 months after the procedure. Induction and maintenance of immunosuppression with triple-drug therapy (cyclosporine, prednisone, and azathioprine) and other combinations that include anti-lymphocyte preparations have led to an overall decrease in the incidence of both cellular and ductopenic rejection. In addition, the availability of FK506 as a rescue therapy has saved grafts in some patients experiencing chronic (ductopenic) rejection. Overall, the correlation between the degree of biochemical liver dysfunction and the presence and severity of histologic rejection remains poor. Histologic severity of rejection, however, suggests which patients will require more immunosuppressive therapy and which patients may need antilymphocyte therapy to control the rejection episode. Some rejection episodes remain resistant to all known therapy and eventually lead to graft loss. New immunosuppressive agents and regimens are needed to improve graft and patient survival, decrease the incidence of cellular and ductopenic rejection, minimize drug-related side effects and complications, and reduce the high cost of immunosuppressive therapy.

Graft Rejection↗
PubMed1994

Etiology and incidence of unconjugated hyperbilirubinemia after orthotopic liver transplantation.

OBJECTIVES: Gilbert's syndrome, or slow bilirubin glucuronidation phenotype, is a common cause of benign hyperbilirubinemia in the general population. There have been only two previously reported cases of Gilbert's syndrome occurring in patients after liver transplantation. This study was conducted to determine the frequency of Gilbert's syndrome in liver transplant recipients. METHODS: The charts of all patients followed by the Mayo Liver Transplant Clinic for 1 yr or more after transplantation, as of June 1992, were reviewed to identify all patients with a consistent pattern of unconjugated hyperbilirubinemia greater than two times the upper limits of normal and with a normal conjugated bilirubin level. These patients were further evaluated to exclude all other causes of hyperbilirubinemia, including biliary obstruction, rejection, viral infection, cholestatic liver disease, and hemolysis. RESULTS: Five of 229 patients (2.2%) had a consistent pattern of unconjugated hyperbilirubinemia. Only three patients (1.3%) had no other identifiable cause of hyperbilirubinemia. CONCLUSIONS: This study was performed to determine the incidence of unconjugated hyperbilirubinemia and particularly to determine the incidence of Gilbert's disease in liver transplant recipients. The apparently low frequency of Gilbert's after liver transplantation may reflect the masking of the diagnosis by other transplant-associated pathology or donor selection bias because of unexplained hyperbilirubinemia. Post-transplant patients who fit the Gilbert's syndrome profile of unconjugated hyperbilirubinemia should have a postprandial bilirubin drawn as a first step. The awareness of this syndrome may avoid a costly and invasive evaluation in the liver transplant recipient.

Bilirubin↗
PubMed1994

Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does not result in sustained improvement in kidney function and causes cellular and ductopenic rejection.

Twelve consecutive liver transplant recipients with stable allograft function and cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an attempt to halt and possibly reverse renal damage. Only patients who met the following criteria were included: (a) triple immunosuppression with cyclosporine, azathioprine and prednisone; (b) stable graft function for at least 1 yr without rejection; and (c) serum creatinine greater than 2.1 mg/dl or renal clearance less than 35 ml/min. Cyclosporine was reduced by 50 mg every 3 wk until discontinuation, prednisone was temporarily increased from 10 to 20 mg/day and azathioprine was maintained at 2 mg/kg/day. Sustained improvement in kidney function in the 12 patients was minimal, with the mean serum creatine level decreasing from 2.5 +/- 0.5 mg/dl (mean +/- S.D.) at study entry to 2.4 +/- 1.2 mg/dl after a mean follow-up of 18 +/- 6 mo. In six patients, histologically confirmed cellular rejection developed after a mean of 5 +/- 6 mo from the time that cyclosporine withdrawal was begun. Two of six patients with rejection responded to bolus steroid therapy and are in stable condition at this writing with low-dose cyclosporine (2.8 and 3.2 mg/kg/day). Two patients initially responded to bolus steroids but later exhibited ductopenic rejection; one responded to treatment with FK 506 and the other died of sepsis. The two remaining patients were steroid unresponsive. One responded to treatment with OKT3 and is now stable on low-dose cyclosporine (2.3 mg/kg/day), but in the other ductopenic rejection developed and the patient died of sepsis during rescue therapy with FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1994

Non-A, non-B fulminant hepatitis is also non-E and non-C.

OBJECTIVES: to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis. METHODS: we utilized the polymerase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients. RESULTS: none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera. Three patients, all with features of autoimmune hepatitis, had raised IgG-HEV antibody titers. Due to the possibility of serologically undetectable hepatitis B virus (HBV) infection in fulminant hepatitis patients, we performed polymerase chain reaction amplification of HBV genomic DNA in acute phase sera of the presumed viral NANB FHF patients and subsequently found no evidence of HBV DNA. CONCLUSIONS: we did not find evidence implicating HCV or HEV in presumed viral NANB FHF or as agents contributing to or causing the liver failure in nonviral NANB FHF patients with autoimmune hepatitis, drug-induced hepatotoxicity, or halothane hepatotoxicity.

Adolescent↗
PubMed1993

Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation.

The clinical significance and outcome of nonanastomotic strictures and dilatations involving only the biliary tree of the graft with a radiological appearance of biliary ischemia is unknown. Therefore we analyzed the grafts of 128 patients to evaluate the biochemical, radiological and histological features that prompted the diagnosis of ischemic-type biliary stricture and the clinical outcome of this complication. Ischemic-type biliary strictures were diagnosed in 25 patients (19%). Initial graft function was similar in all patients, whether or not this complication developed. Most ischemic-type biliary strictures occurred between 1 and 4 mo after orthotopic liver transplantation. However, the appearance of ischemic-type biliary stricture in the month after transplantation was predictive for a poor outcome in all six grafts with early onset of ischemic-type biliary strictures. Eighteen patients (72%) were treated with biliary stents and repeated dilatations. Long-term patency was achieved in 88% of these patients. Repeat transplantation was performed in six patients (24%); five survived. Finally, patients with ischemic-type biliary strictures spent more time in the hospital during the first year after orthotopic liver transplantation than did patients without the complication (62 +/- 27 days vs. 37 +/- 20 days; p < or = 0.001). This was due to repeated hospitalizations and a higher incidence of retransplantation. One-year graft survival was lower in patients with ischemic-type biliary strictures than in patients without ischemic-type biliary strictures (69% vs. 88%; p = 0.006). However, 1-yr patient survival was similar in the two groups (91% vs. 89%). In conclusion, early appearance of ischemic-type biliary stricture features is associated with poor graft prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Hepatic allograft rejection: new developments in terminology, diagnosis, prevention, and treatment.

Hepatic allograft rejection remains a major cause of morbidity related to the need for increased immunosuppression and continues to be a principal cause of late failure of the graft. Hepatic allograft rejection is defined on the basis of morphologic findings; cellular rejection is defined as portal or periportal hepatitis with nonsuppurative cholangitis or endotheliitis (or both), and ductopenic rejection is defined as loss of interlobular and septal bile ducts, typically in at least 50% of the portal tracts. The overall incidence of episodes of cellular rejection, which usually occur within the first 2 weeks after liver transplantation, varies from 50 to 100%. Ductopenic rejection occurs in approximately 8% of patients who undergo initial liver transplantation and is usually diagnosed between 6 weeks and 6 months after transplantation. Induction and maintenance immunosuppression with triple-drug (cyclosporine, prednisone, and azathioprine) therapy and other combinations that include antilymphocyte preparations, however, has decreased the incidence of both cellular and ductopenic rejection. In patients experiencing episodes of cellular rejection, high-dose intravenously administered corticosteroid therapy yields the best response and is associated with a lower incidence of ductopenic rejection than is low-dose and orally administered corticosteroid therapy. The correlation between degree of biochemical liver dysfunction and presence of histologic rejection is minimal early after transplantation. Histologic severity of rejection, however, suggests which patients will require more immunosuppression and which patients may need antilymphocyte therapy for controlling the rejection episode. With the availability of new immunosuppressive agents, distinguishing patients at high risk for rejection is important. The goals for use of new immunosuppressive agents and regimens are to improve graft and patient survival, to decrease the incidence of cellular and ductopenic rejection, and to minimize side effects and complications.

Adrenal Cortex Hormones↗
PubMed1993

Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) predisposes to the development of cholangiocarcinoma, a usually fatal complication that is difficult to diagnose. Serum concentrations of CA 19-9, a tumor-associated antigen, are frequently increased in patients with only cholangiocarcinoma. The aim of this study was to assess the value of an increased serum CA 19-9 level for the diagnosis of cholangiocarcinoma in patients with preexisting PSC. We analyzed serum samples from 9 patients with PSC and superimposed cholangiocarcinoma and from 28 patients with only PSC. Serum concentrations of CA 19-9 were measured in a blinded manner with use of an immunoradiometric assay. The serum CA 19-9 concentrations were increased in 8 of 9 patients (89%) with PSC and cholangiocarcinoma (mean +/- SE, 391 +/- 86 U/ml; range, 4 to 677), whereas they were increased in only 4 of 28 patients (14%) with only PSC (mean +/- SE, 61 +/- 16 U/ml; range, 2 to 370). The sensitivity of a CA 19-9 value greater than 100 U/ml for cholangiocarcinoma in PSC was 89%, and the specificity was 86%. The measurement of serum concentrations of CA 19-9 is a promising test for detecting cholangiocarcinoma in patients with PSC.

Adenoma, Bile Duct↗
PubMed1993

Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis.

We analyzed the immunophenotypes of hepatic cellular infiltrates by quantitative immunohistochemical methods in biopsy specimens from 20 patients with primary biliary cirrhosis (PBC), 19 with primary sclerosing cholangitis, and 11 with autoimmune chronic active hepatitis. Specifically, we sought to identify activated T cells, interferon-gamma-producing cells, and natural killer cells. The portal cellular infiltrate in PBC contained a preponderance of CD4 cells in comparison with CD8 cells, with a CD4/CD8 ratio of 2.45:1. The cellular infiltrate in areas of piecemeal necrosis contained mostly CD8 cells. Infiltrating CD8 cells in PBC had the surface phenotype of cytotoxic (CD8-positive, CD11b-negative) cells. Approximately 4% of T cells expressed interleukin 2 receptors. Interferon-gamma-staining cells were rarely identified (in less than 2%). Cells that expressed the natural killer cell markers CD16, CD56, or CD57 were infrequent, constituting approximately 5% of the cellular infiltrate. The composition of the infiltrates was similar in patients with PBC and chronic active hepatitis. Natural killer cells were twice as common in patients with primary sclerosing cholangitis (P < 0.05) as in those with PBC. The inflammatory infiltrates in areas of piecemeal necrosis were similar in the three diseases and differed from those found within the portal area, in that CD8 cells were preponderant. In all three liver diseases, almost 90% of bile ducts expressed class II HLA antigens. These findings support the hypothesis that cytotoxic T cells of either the CD4 or CD8 immunophenotype but not natural killer cells may be involved in the pathogenesis of PBC and chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: a prospective multivariate time-dependent analysis.

Risk factors for cytomegalovirus and severe bacterial infections were studied prospectively by univariate, multivariate and time-dependent Cox model analysis in 79 consecutive liver transplant patients treated with selective bowel decontamination. Cytomegalovirus infection occurred in 39 patients (49%) and was symptomatic in 22 patients. Twenty-six patients (33%) developed at least one of 43 documented severe bacterial infections. In a multivariate analysis of risk factors for all cytomegalovirus infections, the cytomegalovirus seronegative recipient-cytomegalovirus seropositive donor group was the highest risk group (P < 0.001). Using the same analysis for risk factors for symptomatic cytomegalovirus infections, a prolonged prothrombin time (P < 0.005), a diagnosis of acute fulminant hepatitis as the underlying liver disease (P < 0.01) and a cytomegalovirus seronegative patient receiving a liver from a seropositive donor (P < 0.001) were significant. The treatment with OKT3 therapy (P < 0.008) and hepatic artery thrombosis (P < 0.02) were found to be significant risk factors in a time-dependent univariate analysis but were not independent risk factors when multivariate analysis was utilized. Significant risk factors for major bacterial infections (P < 0.03) using univariate analysis included a prolonged anesthesia, anhepatic and surgical times, as well as the transfusion of large amounts of fresh frozen plasma or autologous blood. In a multivariate analysis, only the transfusion of large amounts of fresh frozen plasma (P < 0.04) was a significant independent risk factor. Cytomegalovirus infection was a risk factor for the development of severe bacterial infections (P < 0.03) in a multivariate time-dependent analysis.

Adult↗
PubMed1993

Complications and risk factors after ileal pouch-anal anastomosis for ulcerative colitis associated with primary sclerosing cholangitis.

OBJECTIVE: This study determined predictive factors for postoperative complications and outcome after ileal pouch-anal anastomosis in patients with ulcerative colitis and primary sclerosing cholangitis. SUMMARY BACKGROUND DATA: Patients with ulcerative colitis and primary sclerosing cholangitis treated by colectomy and ileostomy are at high risk of troublesome bleeding from peristomal varices. METHODS: Postoperative complications and outcome were assessed in 40 patients with ulcerative colitis and sclerosing cholangitis who received an ileal pouch-anal anastomosis between January 1981 and February 1990. RESULTS: Immediate postoperative and remote ileoanal anastomosis-related complications were high but related directly to the severity of liver disease. No patient had perianastomotic anal bleeding. CONCLUSIONS: In patients with both ulcerative colitis and primary sclerosing cholangitis, ileal pouch-anal anastomosis is safe and is not associated with perianastomotic bleeding.

Adult↗
PubMed1993

Increased bile duct complications in liver transplantation across the ABO barrier.

OBJECTIVE: This study evaluated the outcome of liver grafts from ABO incompatible donors, focusing on biliary complications, and compared the results to an ABO compatible control group. Also, the expression of donor ABH antigens in the liver graft was analyzed. SUMMARY BACKGROUND DATA: The outcome of liver transplantation using an ABO incompatible graft is still debated. These blood group related (ABH) antigens are known to be expressed not only on the surface of the erythrocytes, but also on the epithelial cells of large bile ducts. Because the biliary epithelium of hepatic allografts may continue to express donor ABH antigens, it may be more susceptible to immunologic bile duct injury after transplantation across the ABO barrier. METHODS: Eighteen ABO incompatible grafts were compared with 18 ABO compatible grafts in patients who were matched according to medical urgency, primary liver disease (PLD), and recipient age. After transplantation, the grafts were analyzed with cholangiography, Doppler ultrasound, or arteriography and liver histology according to protocol. Immunoperoxidase staining for ABH antigens was performed on hepatic tissue. RESULTS: Biliary complications developed in 82% of the ABO incompatible donors, compared to 6% of the ABO matched controls. Hepatic artery thrombosis occurred in 24%. Cellular rejection was diagnosed in 65% versus only 28% in the control group. The 1-year actuarial graft survival rate was 44% versus 78% in the control group. ABH antigens of the donor were expressed on vascular endothelium and bile duct epithelial cells as long as 150 days after transplant. CONCLUSIONS: Using ABO incompatible allografts, a high incidence of biliary and hepatic artery complications and decreased graft survival in liver transplantation were found. An immunologic injury to the bile duct epithelium and/or to vascular endothelium is suspected.

ABO Blood-Group System↗