Search PubMed⌕ Search

Biomedical subjects

D Van Thiel

Publications and source records attributed to D Van Thiel.

At least 19 recordsLinked to original sources
PubMed1999

Hematopoietic stem cell transplantation from non-replicative hepatitis B virus carriers is safe.

BACKGROUND/AIMS: Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS: A total of 151 patients received an allogeneic hematopoietic stem cell transplantation at the Department of Hematology-Oncology, University of Ankara, between June 1989 and June 1998. Among these, eight HBs-Ag positive and four HBs-Ag negative recipients received a product from a hepatitis B virus positive donor. The median follow-up period for these 12 patients was 13.2 months. RESULTS: Three of the eight HBs-Ag positive recipients died (one from hepatic failure); of the remainder, two are HBs-Ag negative, two HBs-Ag positive with normal liver injury tests and one HBs-Ag positive with elevated ALT levels. Of the four HBs-Ag negative recipients who received stem cells from a hepatitis B positive donor, two died; none of the patients in this group became HBs-Ag positive after transplantation. CONCLUSION: Hepatitis B virus infection is a common problem in patients being considered for allogeneic hematopoetic stem cell transplantation, especially in areas where hepatitis B virus infection is endemic. We believe that the presence of HBs-Ag positivity is not an absolute contraindication for allogeneic hematopoetic stem cell transplantation unless the hepatitis B virus is in a replication phase.

Adolescent↗
PubMed1998

Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon.

Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-alpha often leads to allograft rejection. The aim of the present study was to determine if IFN-alpha therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-alpha was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-alpha with tacrolimus compared with control patients who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v controls 3.3 +/- 4.9 mg daily; P </= .05). Similarly, the mean maintenance dose of prednisone was greater by 2.5 mg daily in patients who received IFN-alpha compared with controls who received CyA-based immunosuppression (IFN-alpha 9.8 +/- 3.1 mg daily v controls 7.3 +/- 3.3 mg daily; P = .01). Acute rejection episodes were detected in 10.5% (n = 11) of IFN-alpha-treated patients compared with 8.8% of controls for the similar time period from OLT and period of exposure to risk of rejection. Mean RAI was 2.0 +/- 2.4 for the IFN-alpha-treated group and 2.1 +/- 1.7 for controls. Rejection episodes with IFN-alpha treatment were mild and responded to steroid therapy. In OLT recipients, the risk of acute rejection was not increased by the introduction of IFN-alpha. However, in this study, patients were exposed to greater levels of immunosuppression.

Biopsy↗
PubMed1998

Effective removal of copper by plasma exchange in fulminant Wilson's disease.

BACKGROUND: Patients who present with fulminant hepatic failure due to Wilson's disease may develop hemolytic anemia and renal insufficiency. In this entity, acute hepatocellular necrosis triggers the release of copper ions into the circulation, which leads to toxic effects on red cell metabolic pathways and hemolysis. STUDY DESIGN AND METHODS: The utility of therapeutic plasma exchange to rapidly remove copper and reduce toxic serum copper levels was studied in two patients with fulminant Wilson's disease. RESULTS: Intensive plasma exchange using fresh-frozen plasma replacement removed substantial amounts of copper from the hypercupremic patients, resulting in a rapid reduction in serum copper levels and decreased hemolysis. The net copper removal was proportional to the serum level, ranging from 7,000 to 11,800 micrograms per procedure in one patient and from 3,700 to 6,800 micrograms in the other. CONCLUSION: Plasma exchange allows a rapid reduction in elevated serum copper levels in patients with fulminant Wilson's disease. This leads to an amelioration of hemolytic anemia and provides clinical stabilization until liver transplantation can be performed.

Adolescent↗
PubMed1997

Preoperative serum levels of wild-type and hepatitis B e antigen-negative hepatitis B virus (HBV) and graft infection after liver transplantation for HBV-related hepatocellular carcinoma.

Allograft infection in hepatitis B surface antigen (HBsAg)-positive patients undergoing liver transplant (OLT) is still significant, despite post-transplant prophylaxis with high doses of immunoglobulin to HBsAg. Baseline status and post-OLT levels of viraemia and wild-type and hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) were correlated with the clinical course of 16 consecutive HBsAg carriers. positive for hepatitis B e antibody, with hepatocellular carcinoma who underwent OLT and received permanent post-OLT prophylaxis with antibody to HBsAg (HBsAb). Fourteen patients had less than 10(3) HBV genome equivalents ml(-1) (eq ml[-1]) at baseline and remained HBV free after a median of 36 months following OLT. Two patients with mean pre-OLT viraemia higher than 10(5) genome eq ml(-1) and prevalent HBeAg-negative HBV viraemia before OLT suffered a severe graft hepatitis. Interferon-alpha2b (3 MU m(-2) per day) was able to reduce viraemia in both patients and to revert the clinical course of the infection in one, who remained infection-free 22 months after IFN treatment. Fourteen patients had less than 10(3) HBV genome eq ml(-1) at baseline and remained HBV free, after a median of 36 months following OLT, with permanent HBsAb immunoprophylaxis. These observations suggest that the quantitative analysis of HBV pre-OLT viraemia levels may provide a very useful tool for predicting the ideal time of liver replacement. Clinical trials on the use of antiviral drugs capable of inhibiting HBV serum levels before liver transplantation should be pursued on this premise.

Aged↗
PubMed1997

Isokinetic muscle strength and its association with neuropsychological capacity in cirrhotic alcoholics.

Alcoholic cirrhotics (n = 49), nonalcoholic cirrhotics (n = 42), and normal controls (n = 50) were compared on measures of isokinetic muscle strength and neuropsychological capacity. Alcoholic cirrhotics were deficient on measures of eccentric and concentric muscle movements, compared with normal controls but were not different from nonalcoholic cirrhotics. Nor were differences observed between the two cirrhotic groups on neuropsychological tests of cognitive and psychomotor capacity, suggesting that cirrhosis rather than alcoholism per se is responsible for the manifest deficits. Psychomotor capacity correlated negatively with isokinetic strength in cirrhotic subjects. These findings suggest that muscle weakness, due either directly to advanced liver disease or mediated by subclinical hepatic encephalopathy, accounts for a portion of the variance on the neuropsychological test performance of cirrhotic alcoholics.

Adult↗
PubMed1996

Neuropsychological impairment in a patient with a normal liver and long-standing portacaval anastomosis: studies obtained before and after liver transplantation.

A case report of the neuropsychiatric consequence of long-standing portal caval shunting in a man without intrinsic liver disease is described. Because of his neuropsychiatric status he underwent liver transplantation. Over the succeeding 8 months he had progressive improvement in his neuropsychiatric performance. These data document the adverse effects of portal caval shunting on neuropsychiatric performance in the absence of intrinsic liver disease as well as their reversibility with shunt closure.

Humans↗
PubMed1995

Abstracting capacity in cirrhotic alcoholics: negative findings.

OBJECTIVE: Alcoholic and nonalcoholic cirrhotics and normal controls were compared to determine the extent to which the cognitive deficits frequently observed in alcoholics are attributable to hepatic encephalopathy. METHOD: A battery of neuropsychological tests was administered measuring verbal and nonverbal abstracting capacity. RESULTS: No significant differences between the three groups were observed. Both the alcoholic (n = 43) and nonalcoholic (n = 63) subjects performed comparably to normal controls (n = 21) and the former two groups performed comparably to each other on seven indicators of abstracting capacity. CONCLUSIONS: Deficits in reasoning ability are not invariably associated with chronic alcoholism. In addition, low grade hepatic encephalopathy concomitant to cirrhosis in both alcoholics and nonalcoholics does not impact adversely on abstracting capacity.

Adult↗
PubMed1995

Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis.

The presence of antimitochondrial antibodies (AMA) is a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, the study of these autoantibodies has enabled much information to be accumulated about the specificity of this response. The autoantigens have been identified as components of a functionally related enzyme family, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E2 subunit (PDC-E2) has been determined to be the immunodominant autoantigen. Using a panel of mouse monoclonal antibodies and human combinatorial autoantibodies, it has been demonstrated that patients with PBC, but not controls, have an abnormal expression of either PDC-E2 or a cross-reacting molecule in the apical region of biliary epithelium. Others have shown a similar reaction using rabbit sera directed to PDC-E2. Our previous studies have concentrated on AMA-positive patients. In this study, the presence of PDC-E2, class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells of AMA-positive as well as AMA-negative patients is addressed. Most patients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region of the bile duct epithelial cells of "PDC-E2," increased IgA expression, and little major histocompatibility complex (MHC) class II staining in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E2 on the apical side of their biliary epithelium had anticentromere antibodies and Sjögren's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

FK506 enhances fibrogenesis in in vitro and in vivo models of liver fibrosis in rats.

BACKGROUND/AIMS: The immunosuppressant FK506 is undergoing clinical trials in transplantation and autoimmune diseases. FK506 modulates several cytokines and exerts hepatoprotection in acute models. This study was initiated to determine whether FK506 would be beneficial as an antifibrogenic agent. METHODS: Fibrosis was induced by carbon tetrachloride administration to rats. Half of those animals were treated with FK506. The rats were killed after 8 weeks of carbon tetrachloride treatment. The livers were evaluated by histology, Northern hybridizations, and collagen quantitation. Additionally, rat fibroblasts were incubated with and without FK506 and used for Northern hybridization analysis. RESULTS: Surprisingly, FK506 exacerbated hepatic inflammation and fibrosis. Increased hepatic collagen and higher messenger RNA levels of transforming growth factor beta 1 and collagens I, III, and IV were found in the FK506-treated group. Rat fibroblasts treated with FK506 expressed higher levels of collagens I and III, fibronectin, macrophage-colony stimulating factor, tissue inhibitor of metalloprotease, and transforming growth factor beta 1 messenger RNAs. CONCLUSIONS: These findings suggest that FK506 increases the expression of extracellular matrix genes and enhances fibrosis in the rat model. While further studies are needed to elucidate these profibrogenic mechanisms, caution is indicated for the unrestricted use of FK506 in patients subject to recurrent fibrogenic stimulation.

Animals↗
PubMed1994

Disease gravity and urgency of need as guidelines for liver allocation.

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe.

Adult↗
PubMed1994

Survival following organ transplantation in an Oklahoma institution, 1985-1993.

Since 1985, a total of 413 patients have undergone 439 solid organ transplants at the authors' institution. The current actuarial one-year survival rate of patients undergoing heart, kidney, lung, or liver transplantation at our center is 94%, 90%, 87%, and 91%, respectively. Five-year survival of heart and kidney recipients is 80% and 75%, respectively. In view of these excellent results and the excellent quality of life that successful organ transplants provide patients with end-stage organ failure, every possible effort should be made to increase organ donation.

Actuarial Analysis↗
PubMed1993

Fasting enhances the effects of anoxia on ATP, Cai2+ and cell injury in isolated rat hepatocytes.

The effect of fasting and anoxia on the intracellular concentration of ATP, Na+, Ca2+, Mg2+, and H+ was studied in isolated perfused rat hepatocytes. ATP and intracellular Mg2+ were measured by 31P-NMR spectroscopy, cytosolic free calcium was measured with aequorin, intracellular Na+ with SBFI, intracellular pH with BCECF, lactic dehydrogenase by NADH absorbance. In hepatocytes from fasted rats, intracellular ATP was depressed 52% (P < 0.001), Nai+ was increased 70% from 16.9 to 27.7 mM (P < 0.02), and Cai2+ was increased 79% from 137 to 245 nM (P < 0.05) when compared to fed rats. Mgi2+ and pHi were unchanged. During anoxia, ATP and the cell phosphorylation potential decreased 90% to practically the same low levels in both fed and fasted groups. On the other hand, in hepatocytes from fasted animals, Cai2+ increased faster and to significantly higher levels than in hepatocytes from fed rats: Cai2+ reached 2.19 microM in 10 min compared to 1.45 microM in 1 h, respectively (P < 0.05). Cell injury assessed by LDH release and trypan blue exclusion also occurred earlier and was more severe in hepatocytes from fasted rats. Fructose and Ca(2+)-free perfusion reduced the rise in Cai2+, abolished LDH release and significantly improved the cell viability measured by Trypan blue exclusion. The data demonstrate that fasting decreases the hepatocytes energy potential and increases Nai+ and Cai2+ which are inversely related to the cell energy potential. Consequently, in hepatocytes isolated from fasted rats, the increase in Cai2+ and the resulting cell injury evoked by anoxia occur earlier and are more severe than in fed rats. These results suggest that Ca2+ plays a crucial role in the development of anoxic cell injury.

Adenosine Triphosphate↗
PubMed1993

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution.

The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation.

Adenosine↗