Biomedical subjects

C Y Chan

Publications and source records attributed to C Y Chan.

At least 19 recordsLinked to original sources

PubMed1997

Analysis of tumor thiol concentrations: comparison of flow cytometric with chemical and biochemical techniques.

The importance of glutathione (GSH) in contributing to cancer therapy resistance is well established. Various advantages may accrue from the ability to determine the distribution of GSH content in individual tumor cells disaggregated from solid tumors using flow cytometric techniques compared with biochemical or chemical measurements of the average GSH level in bulk tissue samples. The flow cytometric technique requires a thiol-reactive fluorescent adduct which is stable and which can differentiate cellular GSH from protein thiols. Thiol-reactive compounds specific for GSH require facilitated conjugation by endogenous cellular enzymes, but such compounds have not been found to accurately monitor GSH in human cells. Compounds which react generally with all thiols require a GSH-depleted calibration control to assess GSH vs. non-GSH components of fluorescent-adduct formation. Our report addresses this question, and compares three different thiol assays in several cell lines. We have found a simple way to control for non-GSH adduct formation. This involves a selective permeabilization process to release low molecular weight adducts (dominated by GSH and cysteine). In application to the desired goal of assessing the distribution of GSH in cells disaggregated from tumors, we have identified a problem with cell-line-specific thiol loss during the tumor cell disaggregation process.

Animals↗

PubMed1997

Safety and immunogenicity of inactivated hepatitis A vaccine in patients with chronic liver disease.

The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV) seronegative patients with chronic liver disease (56 chronic hepatitis B and four chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA units of the inactivated hepatitis A vaccine at month 0, and a booster at month 6. Anti-HAV seroconversion (> or = 33 mIU/mL) was 57.6% (34/59) on day 15, and reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All vaccinees had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive at month 12. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409 mIU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the vaccine doses administered were followed by mostly minor reactions. The majority of symptoms reported were local, all of which resolved within 3 days after vaccination. No significant changes in serum liver enzyme levels were detected after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients with chronic liver disease while the immune response was inferior to that observed in healthy subjects reported in a previous study.

Adolescent↗

PubMed1997

The role of hepatitis G virus infection in patients with acute posttransfusion hepatitis in Taiwan.

BACKGROUND & AIMS: Hepatitis G virus (HGV) has been recently identified as a new transfusion-transmissible agent. This study was performed to evaluate the role of HGV infection in patients with acute posttransfusion hepatitis in Taiwan. METHODS: Sera from 63 patients with acute posttransfusion hepatitis and 61 patients with normal serum aminotransferase levels after transfusion were tested for HGV RNA by reverse-transcription polymerase chain reaction. RESULTS: Six of the 63 patients (9.5%) with acute posttransfusion hepatitis were positive for HGV RNA in pretransfusion sera; 4 were superinfected with hepatitis C virus (HCV) after transfusion and 3 developed chronic hepatitis. Seven (12.3%) of the remaining 57 patients had acute posttransfusion HGV infection; 5 were coinfected with HCV and 2 infected with HGV alone. None with acute HGV infection alone developed chronic hepatitis, whereas 4 of 5 patients (80%) with acute HGV and HCV coinfection developed chronic hepatitis. The clinical course of acute HGV and HCV coinfection was similar to that of acute HCV infection alone. Four of 61 subjects (6.6%) with normal serum aminotransferase levels after transfusion were subclinically infected with HGV. CONCLUSIONS: HGV infection accounted for 12.3% of acute posttransfusion hepatitis in Taiwan before anti-HCV screening of blood donors. The clinical course of acute posttransfusion HGV infection alone was relatively benign.

Acute Disease↗

PubMed1997

Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

Adult↗

PubMed1997

In-vitro activities of aminoglycoside-aminocyclitols against mycobacteria.

Aminoglycoside-aminocyclitols including streptomycin, kanamycin, capreomycin and amikacin showed considerable activity against Mycobacterium tuberculosis, with MICs well below their Cmax and relatively low MBC/MIC ratios. Kanamycin, capreomycin and amikacin remained highly active against 'resistant' and 'multidrug-resistant' M. tuberculosis isolates except for some 'multidrug-resistant' isolates which showed complete cross-resistance between streptomycin and the selected 2-deoxystreptamines. Gentamicin displayed anti-tuberculous activity but was bacteriostatic only. Non-tuberculosis mycobacteria, in particular Mycobacterium chelonae and Mycobacterium avium-intracellulare, were more resistant than M. tuberculosis. Amikacin was inhibitory against Mycobacterium kanasii, Mycobacterium scrofulaceum and Mycobacterium fortuitum, but was bactericidal against M. scrofulaceum only. Kanamycin was also bactericidal against M. scrofulaceum. Growth of M. fortuitum was inhibited by amikacin and neomycin which was also inhibitory against M. tuberculosis and M. scrofulaceum. Although the application of neomycin has been limited by its high toxicity, this study suggested that this drug might be useful as a topical agent for cutaneous infections by M. fortuitum.

Amikacin↗

PubMed1997

Hepatitis B infection and changes in interferon-alpha and -gamma production in patients with systemic lupus erythematosus in Taiwan.

According to previous reports, the prevalence of hepatitis B virus (HBV) infection in patients with systemic lupus erythematosus (SLE) is varied. There has been no report on Taiwan, a hyperendemic area for HBV infection. Furthermore, impaired production of interferon (IFN) in peripheral blood mononuclear cells (PBMC) has been reported to be potentially pathogenic to both chronic HBV infection and SLE. However, the production of IFN in patients with both diseases coexisting is unknown. The aims of this study were to evaluate the prevalence of HBV infection in lupus patients in Taiwan and to measure the production of IFN in patients with both diseases coexisting. One hundred and seventy-three consecutive lupus patients and a control group of 692 age- and sex-matched healthy subjects were included for evaluation of the prevalence of HBsAg. Four groups of subjects (patients with SLE and HbsAg, SLE, chronic hepatitis B and normal controls) were selected for evaluation of the in vitro production of IFN-alpha and -gamma. Six (3.5%) of the 173 SLE patients were positive for HBsAg, which was significantly lower than that of controls (14.7%; P < 0.0001). Patients with coexistent SLE and chronic HBV infection had less lupus activity, including less proteinuria (P = 0.02) and a lower serum titre of anti-double stranded DNA antibodies (anti-dsDNA; P = 0.04), than HBsAg-negative lupus patients. The in vitro production of IFN-alpha in patients with chronic hepatitis B was significantly lower than in those patients with SLE or in the normal control group (P < 0.01). The yields of IFN-alpha and -gamma in patients with coexistent SLE and chronic HBV infection were significantly different from those patients with SLE alone (P < 0.05), but close to those of patients with chronic HBV infection. In conclusion, the prevalence of HBsAg carriers is significantly lower in lupus patients in Taiwan. Patients with coexistent SLE and chronic HBV infection had less lupus activity. Interferon-alpha and -gamma may play a role in the above phenomenon.

Adult↗

PubMed1997

Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C.

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto-antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.

Age Factors↗

PubMed1997

Clinical evaluation of primary biliary cirrhosis in Chinese patients without serum anti-mitochondrial antibody.

BACKGROUND: Primary biliary cirrhosis (PBC), a chronic, progressive, cholestatic liver disease characterized by frequent presence of the anti-mitochondrial antibody (AMA), is rarely seen in the Asian population. Whether or not the presence of AMA alters the clinical, serological and histological features of the disease remains unclear. METHODS: During the 25-year period from 1972 to 1996, 71 Chinese patients with PBC who were diagnosed clinically and/or histologically were reviewed. Seventeen (24%) of them repeatedly tested negative for serum AMA. Clinical, biochemical, immunological, histological data and treatment response to ursodeoxycholic acid were compared between PBC patients with positive and negative serum AMA. RESULTS: Mean serum immunoglobulin M (IgM) level was significantly lower in AMA-negative PBC patients when compared with AMA-positive PBC patients (422 +/- 163 vs. 651 +/- 412 mg/dL, p = 0.042). Serum anti-nuclear antibodies (ANA) were positive in 93% of the AMA-negative PBC patients, a significantly higher percentage when compared with the 66% of AMA-positive patients (p = 0.048). There were no significant differences with regard to age, sex, clinical manifestations, liver biochemistries, histological findings, survival and response to 1-year ursodeoxycholic acid treatment between the AMA-negative and AMA-positive patients. Univariate logistic regression analysis showed relatively lower serum IgM levels, positive serum ANA and anti-centromere type ANA were significant predictive factors to negative serum AMA in PBC patients (p = 0.035, 0.044 and 0.029, respectively). Multi-variate analysis revealed relatively lower serum IgM levels were the only independent significant predictor to negative serum AMA in PBC patients (p = 0.015). CONCLUSIONS: Twenty-four percent of Chinese patients with PBC were negative for serum AMA. AMA-negative PBC patients were characterized by relatively lower serum IgM levels and a higher rate of positive serum ANA.

Adult↗

PubMed1997

The effects of ursodeoxycholic acid in patients with severe obstructive jaundice after drainage procedure.

BACKGROUND: The aim of this study is to evaluate the therapeutic effect of ursodeoxycholic acid (UDCA) for patients with severe obstructive jaundice after drainage procedure. METHODS: From September 1993 to December 1994, patients admitted with severe obstructive jaundice (serum bilirubin > 15 mg/dl) and successful drainage were enrolled into our study. They were randomly divided into two groups to receive UDCA 600 mg per day (UDCA group) or a placebo (placebo group) until operation or discharge. Bile drainage amount, clinical symptoms and signs and adverse effects of drugs were recorded daily. Biochemical tests, including albumin, total bilirubin, cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and prothrombin time, were checked first, on the third and seventh days, and then two weeks after drainage. RESULTS: Thirty-eight patients (M/F = 36/ 2, mean age 66.6 +/- 6.4 years) completed the study, 18 in the UDCA group and 20 in the placebo group. There were no differences in age, sex, causes of obstructive jaundice or methods of drainage procedure between the UDCA and placebo groups. Improvement in biochemical test results were noted in both groups. However, bile drainage amount and changes in liver biochemical test, especially the decrement of serum bilirubin, were not significantly different between both groups. CONCLUSIONS: UDCA seemed not to benefit patients with severe obstructive jaundice after successful drainage.

Aged↗

PubMed1996

Cyclosporin A: drug discontinuation for the management of long-term toxicity after liver transplantation.

After liver transplantation, long-term cyclosporin A (CsA) administration is commonly complicated by renal insufficiency and other side effects. To manage these problems, 1.5 to 2.0 mg x kg(-1) x day(-1) of azathioprine for at least 6 weeks was prescribed; CsA was then discontinued or reduced to < or = 2.5 mg x kg(-1) x day(-1) for several months. The dose of prednisone was kept constant. CsA was discontinued in 14 patients because of nephrotoxicity (three or more serum creatinine levels of > or = 1.5 mg/dL), in 1 patient because of headaches and in 1 patient because of a generalized sensory neuropathy; 1 patient refused to continue taking the drug. The CsA dose was reduced in 13 patients, 12 because of nephrotoxicity and 1 because of headaches. One patient in whom administration of CsA was stopped developed azathioprine hepatotoxicity, whereas 1 patient whose dose was reduced developed acute cellular rejection. These complications were controlled by discontinuing azathioprine and reinitiating CsA. In the patients in whom CsA was discontinued, the mean serum creatinine level decreased from 2.42 +/- 0.48 to 1.72 +/- 0.39 mg/dL (P = .00004); in the patients in whom CsA was reduced, the mean serum creatinine level decreased less markedly. This report suggests that discontinuation of CsA along with increased doses of azathioprine is safe for some patients and may be effective in managing CsA-related nephrotoxicity and other side effects after liver transplantation. Additional studies are needed to determine whether this approach is safe and effective for the growing number of post-transplantation patients who may be candidates for such therapy.

Adult↗

PubMed1996

Comparison of three different hybridization assays in the quantitative measurement of serum hepatitis B virus DNA.

The measurement of hepatitis B virus (HBV) DNA, is important for monitoring and evaluating the efficacy of anti-viral agents in the treatment of patients with chronic hepatitis B. Three different hybridization assays for quantitative measurement of HBV DNA: direct membrane (dot-blot) hybridization, liquid hybridization (Abbott HBV DNA assay) and branched DNA signal amplification assay (Quantiplex, Chiron), were applied to 114 serial serum samples obtained from 13 patients with chronic active hepatitis B who had received ribavirin 600 mg daily for four weeks. Among the three assays, the correlation was found to be highest between Quantiplex and Abbott HBV DNA assay (r = 0.71, p < 0.01), moderate between Quantiplex and dot-blot hybridization (r = 0.58, p < 0.01) and lowest between dot-blot hybridization and Abbott HBV DNA assay (r = 0.27, p < 0.01). Quantiplex detected 107 (94%) of 114 specimens and was the most sensitive assay. All specimens positive by dot-blot hybridization and Abbott HBV DNA assays were detected positive by Quantiplex. The Dot-blot hybridization assay detected all 89 (100%) specimens with a high HBV DNA level (> or = 10 million genome equivalent (Meq)/ml by Quantiplex), but detected only 7 (50%) of 14 specimens with a low HBV DNA level (< 10 Meq/ml). The Abbott HBV DNA assay detected 85 (95%) of 89 specimens with a high HBV DNA level, but detected only 3 (17%) of 18 specimens with a low HBV DNA level. Among 7 negative specimens in the Quantiplex assay, 2 were detected positive by polymerase chain reaction. In conclusion, Quantiplex assay was more sensitive than Abbott HBV DNA assay and dot-blot hybridization assay for quantitative measurement of serum HBV DNA and can be used in the evaluation of the therapeutic drug effect on chronic hepatitis B patients.

Alanine Transaminase↗

PubMed1996

Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival.

BACKGROUND/AIMS: Interleukin-8 (IL-8), a cytokine produced by a host of cells, including monocytes, macrophages, Kupffer cells and hepatocytes, can activate neutrophils. Peripheral neutrophilia and liver neutrophil infiltration are frequently noted in patients with alcoholic liver disease. However, the relationship between IL-8 and different stages of alcoholic liver disease is uncertain. The aim of this study is to determine if a correlation exists between circulating IL-8 levels and biochemical and histological parameters and survival in alcoholic liver disease. METHODS: Serum levels of IL-8 were determined with an enzyme-linked immunosorbent assay in 166 subjects, consisting of 30 healthy controls, 26 patients with non-alcoholic fatty liver, 15 with alcoholic fatty liver, 32 with alcoholic hepatitis, 30 with alcoholic cirrhosis, 28 with chronic hepatitis B and 5 with chronic hepatitis C. RESULTS: Serum IL-8 levels were markedly elevated in patients with alcoholic hepatitis (437 +/- 51 pg/ml) when compared with all other groups (p < 0.05). Levels of IL-8 in patients with alcoholic fatty liver, alcoholic cirrhosis and viral hepatitis were higher than those in controls and in patients with non-alcoholic fatty liver. In addition, IL-8 levels were higher in patients who died (p = 0.007), and correlated with biochemical and histological parameters, and severity of liver injury: serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, prothrombin time, indocyanine green retention ratio, tumor necrosis factor-alpha and peripheral neutrophil count in patients with alcoholic hepatitis. After a 2-year follow up, patients with IL-8 above 479 pg/ml had a higher mortality rate in the alcoholic hepatitis group (p = 0.033). CONCLUSIONS: These findings suggest that IL-8 is activated in alcoholic liver disease, especially in alcoholic hepatitis, and is closely correlated with liver injury. IL-8 levels can reflect the stage and severity of alcoholic liver disease, and may serve as a predictor of survival in patients with alcoholic hepatitis.

Adult↗

PubMed1996

A prospective randomized control study of oral nystatin prophylaxis for Candida peritonitis complicating continuous ambulatory peritoneal dialysis.

A prospective randomized study of the prevention of candida peritonitis (CP) in continuous ambulatory peritoneal dialysis patients using oral nystatin given concomitantly with antibiotic therapy was carried out for 2 years. Patients were randomized into two groups. Nystatin tablets 500,000 units four times a day were given to group 1 but not group 2 patients whenever antibiotics were prescribed. There were 199 patients at risk (mean follow-up, 18.0 months) in group 1 and 198 patients at risk (mean follow-up, 16.6 months) in group 2. The peritonitis and antibiotic prescription rates were comparable between the two groups. There were four episodes of CP in four patients in group 1 and 12 episodes in 11 patients in group 2. The probability of CP-free survival at 2 years was higher in group 1 compared with group 2 (0.974 v 0.915; P < 0.05). However, only three (75%) CP episodes in group 1 and six (50%) in group 2 were considered "antibiotics related." The incidence of antibiotics-related CP was 1.39 and 3.19 per 100 peritonitis episodes and 0.66 and 1.43 per 100 antibiotic prescriptions in groups 1 and 2, respectively (P = NS). We conclude that oral nystatin prophylaxis with each antibiotic prescription reduced the rate of CP in patients on continuous ambulatory peritoneal dialysis irrespective of its apparent temporal relationship to antibiotic prescription.

Administration, Oral↗

PubMed1996

Pneumococcal conjugate vaccine primes for antibody responses to polysaccharide pneumococcal vaccine after treatment of Hodgkin's disease.

Thirty-nine previously treated Hodgkin's disease (HD) patients were immunized with 7-valent pneumococcal conjugate vaccine (7-OMPC) followed by one dose of 23-valent polysaccharide pneumococcal vaccine (23-PS). To determine the priming effect of 7-OMPC vaccine, their antibody responses to six serotypes contained in both vaccines were compared to those of 57 HD patients who received 23-PS vaccine only. The geometric mean antibody concentrations after immunization with 23-PS vaccine were significantly higher for five of the six measured serotypes in HD patients primed with 7-OMPC vaccine compared with responses in HD patients who received 23-PS vaccine only. The mean of the six antibody concentrations was significantly higher for the primed group at 12.5 micrograms/mL and 7.76 micrograms/mL, respectively (P = .015). Priming with a conjugate vaccine should be considered as a strategy to protect high-risk adults.

Adolescent↗

PubMed1996

Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension.

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham-operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4, and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein-ligated rats was similar to that of sham-operated rats and progressively increased, thereafter, reaching statistically higher values days 4 and 14. No differences in plasma endotoxin levels were found between portal vein-ligated and sham-operated rats throughout the observation period. Both carbon tetrachloride-induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6 +/- 2.0 pg/mL; P < 0.01) than those of control rats (2.2 +/- 0.3 pg/mL) and cirrhotic rats without ascites (2.4 +/- 0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.

Animals↗

PubMed1996

Prognostic factor analysis of fulminant and subfulminant hepatic failure in an area endemic for hepatitis B.

In order to determine the criteria in selecting candidates for orthotopic liver transplantation (OLT), we assessed the aetiology and prognostic indicators in 61 patients with fulminant or subfulminant hepatitis during the past 13 years. Several previously reported models of high risk predictors were not suitable for a large portion of our patients with different aetiological and ethnic backgrounds. In the present study, serological markers of various hepatitis viruses were tested and clinical parameters were compared between survivors and non-survivors. Multiple virus infection and multifactorial causes were important in the pathogenesis (48%) of acute liver failure. Among the 13 clinical parameters, six were considered significant on univariate analysis: prothrombin time prolongation (P < 0.001), total bilirubin, creatinine and alpha-fetoprotein (P < 0.01), age and cholesterol (P < 0.05). With stepwise logistic regression using most discriminatory cut-off values, an age of > 43 years (P = 0.0001), total bilirubin levels of > 23 mg/dL (P < 0.005) and prothrombin time prolongation > 19 s (P < 0.0001) were independent predictors of non-survival. When applied to determine the index of poor prognosis, the sensitivity, specificity, positive predictive value, negative predictive value and predictive accuracy were 100, 67, 95, 100 and 95%, respectively, in the presence of any one of these prognostic factors. We conclude that these indicators may be useful for selecting patients with acute liver failure indicated for OLT.

Adolescent↗

PubMed1996

Biodistribution of the nitroimidazole EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide) in mice bearing subcutaneous EMT6 tumors.

The characteristic reduction and binding of nitroimidazoles to cellular macromolecules in the absence of oxygen allows their use for detection and characterization of hypoxia. The biodistribution of a new nitroimidazole, EF5 (2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide), in mice bearing EMT6 tumors is described. Detection methods based on radioactivity and monoclonal antibody techniques are compared for liver and tumor. All nonexcretory tissues demonstrated similar levels of radioactivity at 0.5 hr postinjection of drug, demonstrating equivalent access of EF5 to all tissues. At 24 hr, when unbound drug has been cleared, the tissues with the highest binding are the liver, esophagus, bladder and tumor. Typically, liver tissue contains the highest level of radioactivity at this time. Examination of tumor and liver tissue by use of fluorescence microscopy and Cy3-bound monoclonal antibodies specific for EF5 adducts showed that the patterns of binding in tumor are considerably more heterogeneous than those of liver. Histograms of fluorescence intensity, with use of these antibodies, demonstrate average and maximal binding higher in tumors than in the liver. This divergence from the radioactivity data was determined to be unrelated to sampling error, differential antibody access or staining efficiency of liver vs. tumor tissue. A possible cause is the scavenging of radioactive drug metabolites by liver. The data presented herein suggest that EF5 is useful as a hypoxia detector and that monoclonal antibody detection methods can give detailed information on the distribution of EF5 binding. This technology may allow an accurate estimation of the oxygenation and/or nitroreductase levels in both tumor and normal tissues.

Animals↗

PubMed1996

Single dose-inactivated hepatitis A vaccination schedule for susceptible youngsters.

OBJECTIVE: To investigate the feasibility of a single-dose primary hepatitis A vaccination for young travelers. METHODS: One hundred and nineteen susceptible youngsters, 9-18 yr old, received a dose of 720 ELISA units of the inactivated hepatitis A vaccine at month 0, and then a booster at month 6. RESULTS: Antibodies to hepatitis A virus (anti-HAV) seroconversion ( > or = 20 mIU/ml) in these vaccinees was 91% (106/117) on day 15, and reached 99% (118/119) 1 month after the single-dose vaccination. At month 6 before the booster, 97% (110/113) of the vaccinees still had detectable anti-HAV. All vaccinees (113/113) had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive (68/68) at month 12. The anti-HAV response was found to be slower in vaccinees positive for hepatitis B surface antigen (11/16, 68.8%), compared with noncarrier vaccinees (95/101, 94.1%; p < 0.01) 15 days after the priming dose. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 220, 255, 117, 3308, and 1094 mIU/ml at day 15 and months 1, 6, 7, and 12, respectively. CONCLUSION: These results suggest that a single dose of hepatitis A vaccine could be a good alternative to immune serum globulin administration for immunoprophylaxis in young healthy travelers.

Adolescent↗