bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal evaluation of the pharmacokinetics of cyclosporin microemulsion (Neoral®) in pediatric renal transplant recipients and assessment of C2level as a marker for absorption
Authors: Trompeter Richard , Fitzpatrick Margaret , Hutchinson Carol , Johnston Atholl 
Published: July 2003

Abstract:Background:There are important differences in CsA pharmacokinetics between adult and pediatric patients, such that pharmacokinetic data can not necessarily be extrapolated from the adult to the pediatric setting. Research in adult renal transplant patients has shown that adequate cyclosporin exposure (AUC0−4) in the first week post‐transplant is important for successful clinical outcome, and that cyclosporin concentration at 2 h post‐dose (C2) provides the optimal single‐time point marker for AUC0−4. Clinically, dose management based on C2level results in a low incidence of acute rejection in the adult renal transplant population. The study reported here undertook pharmacokinetic profiling inde novorenal transplant patients over a period of 6 months and retrospectively assessed alternative monitoring strategies based on pharmacokinetic findings and clinical outcomes.Methods:This open‐label, observational, prospective study was carried out at four UK transplant centers over a period of 6 months in pediatricde novorenal transplant recipients receiving the microemulsion formulation of cyclosporin (Neoral®) according to local protocol. Twelve‐hour pharmacokinetic profiles (8–16 blood samples each) were performed on days 5 and 14 and at weeks 4, 13 and 26 post‐transplant.Results:Thirty‐two patients were recruited (median age 10 yr, range 3–18 yr). At 6 months, patient survival was 100% and graft survival was 91%. The incidence of clinically determined acute rejection was 41% (13 of 32). Six patients discontinued Neoral before 6 months: three due to graft loss, one due to rejection, one due to renal toxicity and one due to hypertrichosis. At all time points studied, C2correlated more closely with AUC0−4and with AUC0−12than did the pre‐dose cyclosporin concentration (C0, or trough). Patients achieving C2 > 1.5 μg/mL by the fifth postoperative day experienced no acute rejection in the first 6 months, compared with a 50% rejection rate among patients with C2 < 1.5 μg/mL (P < 0.05). Binary logistic regression analysis showed that C2level >1.7 μg/mL was associated with approximately 90% probability of freedom from acute rejection. Analysis of renal function across patients grouped according to cyclosporine exposure (AUC0−4, C2) showed no adverse effects of higher/increased exposure on creatinine or GFR.Conclusions:C2level provides a more reliable marker for CsA exposure than C0in pediatric renal transplant recipients, and is more closely predictive of acute rejection risk. A C2target of 1.7 μg/mL appears appropriate in this population during the immediate post‐transplant period in order to maximize clinical benefit.
Non‐cardiogenic pulmonary edema during basiliximab induction in three adolescent renal transplant patients
Authors: Bamgbola Fatai O. , Rio Marcela Del , Kaskel Fredrick J. , Flynn Joseph T. 
Published: July 2003

Abstract:  Background:  Introduction of the anti‐CD‐25 mAb basiliximab into renal transplant protocols has reduced the incidence of acute rejection. However, its side‐effect profile is still unfolding. We report three adolescents who developed severe non‐cardiogenic PE within 2 days of renal transplantation.Methods:  Pretransplant cardiorespiratory evaluation was normal in all cases. Transplant immunosuppression consisted of basiliximab induction, corticosteroids, and tacrolimus. Patients received standard fluid management during and after the transplant surgery.Case reports:  Patients 1 and 2 were 17‐ and 21‐yr‐old females. Pretransplant Hct values were 35 and 25% respectively. Each received 5‐L normal saline during surgery. EBL was 200 and 500 mL in patients 1 and 2, respectively. There was immediate post‐operative diuresis. Both developed non‐cardiogenic PE by POD no. 2. BIPAP and PRVC were administered respectively. In both cases PE resolved within 1 wk. Patient 3 was a 19‐yr‐old male with pretransplant Hct of 43% who received a cadaveric renal transplant after 23.5‐h cold‐ischemia; 3.5 L normal saline was given during surgery. EBL was 100 mL. Non‐cardiogenic PE ensued on POD no. 2 warranting assisted ventilation. The patient died following a sudden cardiopulmonary arrest on POD no. 3.Conclusions:  Potential mechanisms for the development of PE include cytokine release from basiliximab with increased capillary permeability, volume overload and ischemic‐reperfusion injury. Improved awareness of this potential complication, prudent fluid management, and efforts to minimize graft‐ischemia are recommended to prevent further cases.
Quantitative analysis of CMV DNA in children the first year after liver transplantation
Authors: Kullberg‐Lindh Carola , Ascher Henry , Krantz Marie , Lindh Magnus 
Published: July 2003

Abstract:CMV infection is a major problem after solid organ transplantation especially in children where primary infection is more common than in adults. Early diagnosis is critical and might be facilitated by quantitative analysis of CMV DNA in blood. In this retrospective study of 18 children who had a liver transplantation 1995–2000, serum samples were analysed by Cobas Amplicor Monitor (Roche). Four patients developed symptomatic CMV infection at a mean time of 4 wk after transplantation. They showed maximum CMV DNA levels in serum of 26 400, 1900, 1300 and 970 copies/mL, respectively. In comparison, CA Monitor was positive, at a low level (415 copies/mL), in one of 11 patients with asymptomatic (4) or latent (7) infection. CMV IgM was detected at significant levels (≥1/80) in all four patients with symptomatic, and in one with asymptomatic CMV infection. Eight patients were given one or several courses of ganciclovir. Five of these lacked symptoms of CMV disease, and had low (415 copies/mL) or undetectable CMV DNA in serum. The data suggest that quantitative analysis of CMV DNA may be of value in early identification of CMV disease and for avoiding unnecessary antiviral treatment.
Alterations of cyclosporin A metabolism induced by mycophenolate mofetil
Authors: Pape L. , Froede K. , Strehlau J. , Ehrich Jochen H. H. , Offner G. 
Published: July 2003

Abstract:Unexpectedly lower CsA 2‐h levels were found in patients who received additional immunosuppression by MMF in our center. The aim of this study is to prove whether there are differences in CsA metabolization when MMF is added to treatment. In 33 children who received an immunosuppression of prednisolone and CsA as well as in 15 children who were treated with additional MMF, C2 and C0 were taken. In 11 children, full AUC of CsA were obtained. C2 levelsdiffered significantly (p < 0.05) between patients treated with (617 ± 230 ng/mL) and without MMF (750 ± 271 ng/mL) but with similar CsA dosages. C2 correlated better with the AUC than CsA levels at other time points with r = 0.95. The equation AUC = 139 + 6.17 × C2 was calculated to match best in a C2‐limited sampling strategy. This formula proved to be safer than equations that had been published before. According to our findings, we suspect that MMF alters the CsA metabolism. When MMF is used in pediatric transplant recipients, either target values of CsA have to be changed or patients may require higher doses of CsA.
Risk of hearing impairment in pediatric liver transplant recipients: A single center study
Authors: Bucuvalas John C. , O'Connor Amy , Buschle Kristen , Krug Susan , Ryckman Frederick C. , Atherton Harry , Alonso Maria P. , Balistreri William F. 
Published: July 2003

Abstract:  As survival rates following liver transplantation have increased, health care providers must assess the impact of transplantation on dimensions other than traditional medical measures. Hearing impairment may adversely impact social, emotional, cognitive, academic, and speech and language development. We hypothesized that children who undergo liver transplantation are at risk for hearing impairment due to exposure to ototoxic drugs. We conducted a review of 74 children who had undergone liver transplantation between December 1996 and September 2000 at Cincinnati Children's Hospital Medical Center. Hearing was assessed at discharge by an audiologist using age and developmentally appropriate techniques. The principal outcome measure was sensorineural hearing impairment. Independent variables were age at transplantation, United Network for Organ Sharing (UNOS) status at transplantation, primary diagnosis, post‐transplant length of hospital stay, days of treatment with aminoglycosides, and days of treatment with loop diuretics. Eleven of 74 children (15%) had sensorineural hearing loss, of whom four had severe to profound hearing loss. Multivariate analyses showed that the adjusted relative risk for hearing loss in patients with hepatoblastoma was 66 and that there was a 5% increase risk for hearing loss for each additional day of hospitalization. Age at transplantation, UNOS status, and days of treatment with loop diuretics or aminoglycosides did not achieve significance in the model. Sensorineural hearing impairment occurs in a subset of pediatric patients following liver transplantation. Patients with hepatoblastoma or those who experience prolonged hospitalization after transplantation are at increased risk. Our observations are of particular importance for pediatric liver transplant recipients since the median age at transplantation is 12–18 months, a critical period for language acquisition.
β‐Glucuronidase inhibitor tectorigenin isolated from the flower of Pueraria thunbergiana protects carbon tetrachloride‐induced liver injury
Authors: Lee Hae‐Woong , Choo Min‐Kyung , Bae Eun‐Ah , Kim Dong‐Hyun 
Published: July 2003

AbstractBackground/Aim: To understand the relationship between the fluctuation in serum β‐glucuronidase and hepatotoxicity, an inhibitor of β‐glucuronidase was isolated from the flowers of Pueraria thunbergiana and its hepatoprotective activity was measured.Method: Tectorigenin was isolated from the flowers of pueria thunbergiana as an inhibitor of β‐glucuronidase, and serum ALT, AST and biological parameters as markers for its hepatoprotective activity were measured on CCl4‐induced liver injury in mice. The relationship between serum β‐glucuronidase and hepatoprotective activities in mice was measured.Results: When tectorigenin at a dose of 100 mg/kg was intraperitoneally administered on CCl4‐induced liver injury in mice, it significantly inhibited the increase of plasma ALT, AST and LDH activities. The inhibitory effect of tectorigenin is much more potent than that of dimethyl diphenyl bicarboxylate (DDB), which has been used as a commercial hepatoprotective agent. When tectoridin transformed to tectorigenin by intestinal bacteria was orally administered to mice, it showed hepatoprotective activity. However, when tectoridin was intraperitoneally administrated to mice, it did not exhibit hepatoprotective activity. Moreover, orally administered tectoridin not only inhibited β‐glucuronidase but also increased GSH content and GST activity on CCl4‐induced hepatotoxicity of mice.Conclusion: We insist that an inhibitor of β‐glucuronidase tectorigenin may be hepatoprotective and tectoridin should be a prodrug transformed to tectorigenin.
Clinical significance of antibody against hepatitis B virus core antigen in patients with hepatitis C virus‐related hepatocellular carcinoma
Authors: Yano Yoichi , Yamashita Fumihiko , Sumie Shuji , Kuwaki Kotaro , Yamamoto Hiroshi , Toyoda Naoko , Ando Eiji , Tanaka Masatoshi , Sata Michio 
Published: July 2003

AbstractPurpose: We investigated the unsettled issue of whether seropositivity for antibody to hepatitis B core antigen (anti‐HBc) affects characteristics of hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC).Methods: Antibody status was determined by enzyme immunoassay in 243 patients with this cancer, and associations with clinicopathologic characteristics and outcome were analysed. Serum hepatitis B virus (HBV) DNA was determined by real‐time polymerase chain reaction.Results: Of 235 patients with unequivocal serologic status, 142 were seropositive and 93 were seronegative. Clinicopathologic characteristics and overall cumulative survival rates were comparable between the two groups. However, seropositivity tended to predict poor outcome for patients in Child class B or C (P=0.068), those in tumour‐nodes‐metastasis‐based stage 3 or 4 (P=0.081), those with tumours exceeding 25 mm (P=0.068), and those with a past history of clinical liver disease (P=0.088). Multivariate analysis identified serum albumin, portal vein tumour thrombosis, and tumour size as independent determinants of survival. Serum HBV DNA was below 1.7 log copies/ml in all 40 patients tested.Conclusions: Overall, the clinical features of HCV‐HCC were unaffected by seropositivity for anti‐HBc. Seropositivity tended to worsen prognosis for subgroup with poor hepatic reserve or advanced tumours.
Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats
Authors: Brown Kyle E. , Dennery Phyllis A. , Ridnour Lisa A. , Fimmel Claus J. , Kladney Raleigh D. , Brunt Elizabeth M. , Spitz Douglas R. 
Published: July 2003

AbstractBackground/Aims: Oxidative stress is presumed to play an important role in hepatic fibrogenesis. Diets high in polyunsaturated fatty acids (PUFA) enhance fibrosis and have been associated with increased oxidative damage in some models of liver injury. The aim of this study was to determine the effects of dietary fat of varying PUFA content on iron‐induced oxidative stress and fibrosis.Methods: Rats were given parenteral iron and diets supplemented with coconut oil, safflower oil or menhaden oil.Results: Hepatic iron overload was associated with induction of heme oxygenase‐1, a sensitive indicator of oxidative stress, and with modest increases in hydroxyproline and procollagen I mRNA levels without histologically evident fibrosis, all of which were unaffected by dietary fat. In addition, iron loading was associated with increases in cysteine, γ‐glutamylcysteine and glutathione. Dietary fat brought about the expected alterations in peroxidizability, but did not alter indices of oxidative damage.Conclusion: These data highlight the distinction between oxidative stress and oxidative damage and suggest that the former is not sufficient to elicit overt fibrosis. Furthermore, while hepatic iron overload leads to oxidative stress, there is an associated upregulation of antioxidant defenses involving thiol metabolism that may be a critical factor limiting the accumulation of oxidative damage.
Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation
Authors: Bal Jasdeep Singh , Thuluvath Paul J 
Published: July 2003

AbstractBackground: A prolonged QTc interval has been reported in patients with liver disease. The objectives of our study were to determine whether a prolonged QTc interval was an independent predictor of mortality in patients with cirrhosis and to examine the effect of liver transplantation (LT) on QTc interval.Patients and methods: We retrospectively studied two cohorts of patients – QTc interval was measured in 409 patients (pre‐transplant group), and in 162 patients (transplant group) before and 6 months after LT. QT interval (mean) corrected (QTc) for ventricular rate was read from a 12‐lead EKG. Patients with known cardiovascular disease or other risk factors that are known to cause a prolonged QTc interval were excluded.Results: Pre‐transplant group. One hundred and sixty‐two patients (40%) had a prolonged QTc interval (>440 ms). By binary logistic regression, age (P=0.005), alcoholic cirrhosis (P=0.007) and Child–Pugh scores (P=0.007) were independent predictors of prolonged QTc interval. Sixty‐six patients died during a mean follow‐up of 8.9 years. Although the Kaplan–Meier survival curve showed a lower survival in patients with a prolonged QTc interval (P=0.03 by log rank test), when survival was adjusted for the Child–Pugh score by Cox regression survival analysis, there were no survival differences in patients with and without prolonged QTc interval. Cox regression analysis showed that the Child–Pugh score (hazard ratio 1.5, CI 1.3–1.6, s<0.001) was the only independent predictor of survival. Transplant group. In this cohort, 91 patients (56%) had prolonged QTc (>440 ms) before LT. Mean QTc improved significantly after LT (429 ± 29 ms vs. 450 ± 39 ms P<0.002). Of the 91 patients with prolonged QTc, 50 (55%) normalized, three (3.3%) remained unchanged, 12 (13.3%) showed further prolongation, and 26 (28%) showed improvement but remained above normal limits. An additional nine patients who had normal QTc before LT developed prolonged QTc (>440 ms) after LT.Conclusion: A prolonged QTc interval was common in patients with cirrhosis, but its presence had no independent effect on mortality. Prolonged QTc returns to normal values in about half of the patients after LT, suggesting that liver disease plays a role, but may not be the only factor in the pathogenesis of prolonged QTc.
No association between GSTP1 gene aberrant promoter methylation and prognosis in surgically resected hepatocellular carcinoma patients from the Basque Country (Northern Spain)
Authors: Anzola Monica , Cuevas Nerea , López‐Martínez Monica , Saiz Alberto , Burgos Juan José , Pancorbo Marian Martínez de 
Published: July 2003

AbstractAims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, being linked etiologically to several factors. Glutathione‐S‐transferases (GSTs) are a family of enzymes that play an important role in detoxification. Hypermethylation of regulatory sequences at glutathione‐S‐transferase pi class gene (GSTP1) has been found in different human tumor types. In this study, we have studied the methylation status of the GSTP1 promoter region in patients from the Basque Country (Northern Spain) by methylation‐specific PCR (MSP).Methods and results: GSTP1 aberrant promoter methylation was present in 24 of 117 (20.5%) tumor samples being associated with late stages of tumor progression. Patients with multiple HCCs showed different patterns of methylation, which could suggest a different clonal origin of multicentric HCC or different degrees of differentiation. No effect on disease‐free survival or overall survival was observed in patients with GSTP1 methylated who underwent curative resection.Conclusions: We can conclude that GSTP1 promoter CpG island methylation appears to be a less common event during hepatocarcinogenesis in European populations than in Asian populations, being associated with late stages of tumor progression. These findings could also be useful to provide new therapeutic strategies through the use of demethylating agents.
High rate of long‐term virological response after a 1‐year course of interferon ± ribavirin in chronic hepatitis C relapsers. Results of a 191 patients randomized trial
Authors: Boucher Eveline J , Jacquelinet Sylvie , Canva Valérie , Turlin Bruno , Jacquelinet Christian , Colimon Ronald , Deugnier Yves , Guyader Dominique , Brissot Pierre 
Published: July 2003

AbstractWe investigated the long‐term efficacy of a 12‐month course of interferon (IFN)+ribavirin in chronic hepatitis C relapsers. We randomized 191 relapsers with a 2:1 ratio to receive 3 million units three times a week of interferon alpha (IFN α)‐2b+ribavirin (1–1.2 g/day) (group A=127 patients) or IFN α‐2b (group B=60 patients) of same dosage and duration for 1 year. General and hepatitis C data of group A and B patients were similar. The main goal of the study was to determine the rate of sustained virological response evaluated 1 year after treatment.Results: Virological sustained response (SR) was 61% and 12% for groups A and B, respectively (P<0.001). A significant histological improvement was observed in both treatment groups. The Metavir activity score became significantly lower in the IFN+ribavirin group than in the IFN group (P<0/0001). The Metavir fibrosis scores remained unchanged. Also, at the end of the treatment, the virological response was 69% (88/127) for group A and 33% (20/60) for group B (P<0.001).Conclusion: One‐year retreatment of relapsers with the combination of IFN+ribavirin led to 61% of virological SR and to a significant improvement of histological activity. Therefore, the therapeutic schedule presented here can be considered of particular interest for the retreatment of relapsers.
Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine
Authors: Muriel Pablo , Deheza Rogelio 
Published: July 2003

AbstractBackground/Aims: To evaluate liver‐beneficial properties of metadoxine, not related with alcohol metabolism, bioactivation of external toxins or antioxidant mechanisms, the chronic bile duct ligation (BDL) model was used and results were compared with colchicine.Methods: Seven groups (n=6) of male Wistar rats were used. Four groups were BDL and received metadoxine (60 mg/kg/12 h i.p.), colchicine (10 μg/rat/day/p.o.), both or vehicles; three groups were sham‐appropriate controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde (MDA) was used to estimate lipid peroxidation levels; glycogen was determined utilizing the anthrone reagent; gomory's trichromic stains of liver sections were performed.Results: Collagen increased four‐fold by BDL, metadoxine, colchicine or both prevented fibrosis partially; MDA levels increased three‐fold by BDL and no treatment had any significant effect; glycogen was almost depleted in the cirrhotic group, metadoxine preserved glycogen; bilirubins, and alanine aminotransferase and γ‐glutamyltranspeptidase activities increased several‐fold in the BDL group, and both drugs prevented these effects partially. The histopathological analysis correlated with biochemical data.Conclusions: Both compounds showed similar antifibrotic properties; metadoxine was more effective in preserving glycogen. Besides its antioxidant effects and its ability to induce alcohol metabolism, metadoxine possesses important antifibrotic and antinecrotic properties, and maintains energy stores efficiently.
Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy
Authors: Steindl‐Munda Petra , Ferenci Peter , Brunner Harald , Nachbaur Karin , Datz Christian , Gschwantler Michael , Hofer Harald , Stauber Rudolf , Hackl Franz , Jessner Wolfgang , Rosenbeiger Martha , Gangl Alfred , Vogel Wolfgang ,   for the Austrian Hepatitis Study Group
Published: July 2003

AbstractBackground/aims: Initial high‐dose interferon‐α induction therapy in combination with ribavirin improves sustained response rates in treatment‐naïve patients. This prospective, randomized, controlled study tested whether non‐responders or relapsers to interferon monotherapy also benefit from induction therapy.Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1–1.2 g ribavirin/day throughout the whole study.Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non‐1 than in those with genotype 1.Conclusion: High‐dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.