bluuebunny/crossref_metadata_2025 huggingface dataset:
Hbv Dna Persistence 10 Years After Liver Transplantation Despite Successful Anti–Hbs Passive Immunoprophylaxis
Authors: Roche Bruno , Feray Cyrille , Gigou Michele , Roque-Afonso Anne Marie , Arulnaden Jean Louis , Delvart Valerie , Dussaix Elisabeth , Guettier Catherine , Bismuth Henri , Samuel Didier
Published: June 2003

Long–term immunoprophylaxis with hepatitis B immune globulin (HBIG) is widely accepted for the prevention of recurrent hepatitis B virus (HBV) infection after liver transplantation in HBV–infected patients without viral replication. We report long–term results of HBIG administration in 284 hepatitis B surface antigen (HBsAg)–positive transplant patients. In protocol 1, 259 patients were given HBIG with the goal of maintaining the anti–HBs antibody (Ab) titer over 100 IU/L. After December 1993, 25 HBV DNA–positive patients received HBIG, with a target anti–HBs Ab titer over 500 IU/L, combined with posttransplantation antiviral therapy (protocol 2). At 10 years, 44 patients without recurrence were tested for the presence of HBV DNA in serum using real–time polymerase chain reaction (PCR); 28 were also tested in liver and peripheral blood mononuclear cells (PBMC). The overall 5– and 10–year posttransplantation actuarial rates of HBV recurrence were 24.2% and 25.4%, respectively. The 5–year recurrence rate in protocol 2 patients was 11.8%. On multivariate analysis, predictors of lower HBV recurrence risk were absence of serum HBV DNA before transplantation (P < .0001), acute liver disease (P = .0037), HDV superinfection (P = .012), and protocol 2 therapy (P < .0001). Low–level HBV DNA was detected by PCR in 45.4% of patients without HBV recurrence at 10 years. Overall actuarial 10–year survival was 74.4%. In conclusion, we confirm the efficacy of long–term HBIG immunoprophylaxis. Combination prophylaxis with HBIG and antiviral therapy is effective in patients with viral replication. Although there were only a few cases of HBV recurrence after 5 years, HBV DNA remained present in 45% of patients at 10 years.
Central Role of Pparα–Dependent Hepatic Lipid Turnover in Dietary Steatohepatitis in Mice
Authors: Ip Emilia , Farrell Geoffrey C. , Robertson Graham , Hall Pauline , Kirsch Richard , Leclercq Isabelle
Published: June 2003

We have proposed that steatohepatitis results from reactive oxygen species (ROS) acting on accumulated fatty acids to form proinflammatory lipoperoxides. Cytochrome P450 4a (Cyp4a) and Cyp2e1 are potential hepatic sources of ROS. We tested the hypothesis that increasing Cyp4a through activation of peroxisome proliferator–activated receptor α (PPARα) should aggravate steatohepatitis produced by feeding a methionine and choline deficient (MCD) diet. Conversely, we assessed dietary steatohepatitis in PPARα-/- mice that cannot up–regulate Cyp4a. Male wild type (wt) or PPARα-/- mice (C57BL6 background) were fed the MCD diet with or without Wy–14,643 (0.1% wt/wt), a potent PPARα agonist. Controls were fed the same diet supplemented with methionine and choline. After 5 weeks, wt mice fed the MCD diet developed moderate steatohepatitis and alanine aminotransferase (ALT) levels were increased. Wy–14,643 prevented rather than increased liver injury; ALT levels were only mildly elevated whereas steatohepatitis was absent. Wy–14,643 up–regulated mRNA for liver fatty acid binding protein and peroxisomal β–oxidation enzymes (acyl–CoA oxidase, bifunctional enzyme, and ketothiolase), thereby reducing hepatic triglycerides and preventing steatosis. In wt mice, dietary feeding up–regulated Cyp4a14 mRNA 2.7–fold and increased hepatic lipoperoxides compared with controls. Wy–14,643 prevented hepatic lipoperoxides from accumulating despite an 18–fold increase in both Cyp4a10 and Cyp4a14 mRNA. PPARα-/- mice fed the MCD diet developed more severe steatohepatitis than wt mice, and were unaffected by Wy–14,643. In conclusion, PPARα activation both increases Cyp4a expression and enhances hepatic lipid turnover; the latter effect removes fatty acids as substrate for lipid peroxidation and is sufficiently powerful to prevent the development of dietary steatohepatitis.
Kinetics of the Immune Response During Hbv and Hcv Infection
Authors: Bertoletti Antonio , Ferrari Carlo
Published: June 2003

The innate immune system has a role not only in protecting the host during the initial period of virus infection, but also in shaping the nature of the adaptive immune response. In this review, we follow the kinetics of the virologic and immunologic events occurring from the time of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We primarily discuss how the early events after infection might influence the development of the adaptive immune response in these 2 important viral infections and how new strategies for more efficient preventive and therapeutic vaccines can be derived from this knowledge.
Ursodeoxycholic Acid Therapy and the Risk of Colorectal Adenoma in Patients With Primary Biliary Cirrhosis: An Observational Study
Authors: Serfaty Lawrence , De Leusse Antoine , Rosmorduc Olivier , Desaint Benoit , Flejou Jean-Francois , Chazouilleres Olivier , Poupon Renée E. , Poupon Raoul
Published: June 2003

Ursodeoxycholic acid (UDCA) is the first–line treatment for primary biliary cirrhosis (PBC). The long–term administration of UDCA might indirectly favor colon carcinogenesis by increasing the fecal excretion of secondary bile acids or, in contrast, it might inhibit colon carcinogenesis, as demonstrated in animal models. In patients with PBC, we examined the effect of prolonged UDCA administration on the prevalence and recurrence of colorectal adenoma and on the proliferation of colon epithelial cells. One hundred fourteen patients (103 women, 11 men; mean age, 55 years) with PBC, were enrolled in a colonoscopic surveillance program. The prevalence of colon adenoma was compared in patients already treated with UDCA (mean duration 46 months) at the time of colonoscopy (treated group, n = 52) and in patients undergoing colonoscopy just prior to treatment initiation (untreated group, n = 62). The recurrence of adenoma following removal (mean follow–up, 35 months) was compared between UDCA–treated patients and appropriate age– and gender–matched controls (2/1) selected from a cohort of 205 patients undergoing polypectomy. Epithelial cell proliferation was assessed using anti–Ki67 antibodies on colon biopsies from both treated and untreated patients. Treated and untreated patients displayed similar demographic characteristics. The prevalence of colorectal adenomas was 13% in the treated group versus 24% in the untreated group (P = .16). The colon epithelial cell proliferation index was significantly lower in treated patients than in untreated patients (P = .001). Following removal of the adenoma, the probability of recurrence was significantly lower in patients treated with UDCA than in controls (7% vs. 28% at 3 years, P = .04). In conclusion, this study suggests that, in patients with PBC, the prolonged administration of UDCA (1) is not associated with an increased prevalence of colorectal adenomas, and (2) significantly decreases the probability of colorectal adenoma recurrence following removal. These results are strengthened by the significant reduction in colon epithelial cell proliferation seen in patients treated with UDCA.
The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club
Authors: Moore Kevin P. , Wong Florence , Gines Pere , Bernardi Mauro , Ochs Andreas , Salerno Francesco , Angeli Paolo , Porayko Michael , Moreau Richard , Garcia-Tsao Guadelupe , Jimenez Wladimiro , Planas Ramon , Arroyo Vicente
Published: June 2003

Ascites is a common complication of cirrhosis, and heralds a new phase of hepatic decompensation in the progression of the cirrhotic process. The development of ascites carries a significant worsening of the prognosis. It is important to diagnose noncirrhotic causes of ascites such as malignancy, tuberculosis, and pancreatic ascites since these occur with increased frequency in patients with liver disease. The International Ascites Club, representing the spectrum of clinical practice from North America to Europe, have developed guidelines by consensus in the management of cirrhotic ascites from the early ascitic stage to the stage of refractory ascites. Mild to moderate ascites should be managed by modest salt restriction and diuretic therapy with spironolactone or an equivalent in the first instance. Diuretics should be added in a stepwise fashion while maintaining sodium restriction. Gross ascites should be treated with therapeutic paracentesis followed by colloid volume expansion, and diuretic therapy. Refractory ascites is managed by repeated large volume paracentesis or insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS). Successful placement of TIPS results in improved renal function, sodium excretion, and general well–being of the patient but without proven survival benefits. Clinicians caring for these patients should be aware of the potential complications of each treatment modality and be prepared to discontinue diuretics or not proceed with TIPS placement should complications or contraindications develop. Liver transplantation should be considered for all ascitic patients, and this should preferably be performed prior to the development of renal dysfunction to prevent further compromise of their prognosis.
Liver organ allocation for hepatocellular carcinoma: Are we sure?
Authors: Marsh Wallis J. , Dvorchik Igor
Published: June 2003

Of patients with hepatocellular carcinoma (HCC), 70% to 90% present with cirrhosis. Accordingly, liver transplantation ∥LT), not liver resection, currently remains the only possibility of cure for these patients. Because there is a severe shortage of liver organ donors, not all patients in need can be offered LT. Therefore, transplant listing criteria simultaneously must determine the greatest number of suitable candidates for transplantation while rejecting the smallest number of those who could benefit from LT. The objective of this study was to determine the outcome of patients with HCC who are denied LT by current listing criteria. Of patients who are being denied liver transplantation by the current United Network for Organ Sharing listing criteria (but who were transplanted before the current guidelines took effect(, 27% to 49% were cured by this procedure. The listing criteria for LT in the presence of HCC should reflect the minimum acceptable )not maximum acceptable) recurrence-free survival rate and must reflect a consensus of the transplant community.
Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation
Authors: Aduen Javier F. , Stapelfeldt Wolf H. , Johnson Margaret M. , Jolles Howard I. , Grinton Stephen F. , Divertie Gavin D. , Burger Charles D.
Published: June 2003

We investigated the clinical significance of time of onset, duration, and type of pulmonary edema after orthotopic liver transplantation by retrospectively reviewing 93 consecutive recipients. Pulmonary edema was diagnosed by means of radiographic criteria and Pao2
/Fio2
ratio <300. Type was identified by pulmonary artery wedge pressure (hydrostatic, >18 mm Hg; permeability, ≤18 mm Hg). Of 91 evaluable patients, 44 (48%) had no pulmonary edema, 23 (25%) had immediate pulmonary edema resolving within 24 hours, 8 (9%( had late pulmonary edema (developing de novo in the first 16 to 24 hours), and 16 (18%) had persistent pulmonary edema (developing immediately and persisting for at least 16 hours). At 16 to 24 hours, mean arterial pressure was lower with persistent permeability-type edema than without pulmonary edema (75 versus 87 mm Hg, P < .01). Patients with persistent permeability-type edema had higher mean pulmonary arterial pressure (23 versus 16 mm Hg, P < .01) and higher pulmonary vascular resistance (103 versus 53 dyn · second · m−5, P < .05), consistent with a resistance-dependent mechanism. Patients with persistent hydrostatic-type edema did not differ from those without edema in mean arterial pressure (84 versus 87 mm Hg, P > .05) or pulmonary vascular resistance (67 versus 53 dyn · second · m−5, P > .05), but had increased mean pulmonary arterial pressure (27 versus 16, P < .01), suggesting a flow volume-dependent mechanism. Duration of mechanical ventilation, intensive care, and hospital stay were prolonged in patients with late or persistent permeability-type edema but not in patients with immediate pulmonary edema of any type. In conclusion, immediate pulmonary edema resolving within 24 hours after liver transplantation had little clinical consequence; persistent permeability-type pulmonary edema portended a worse outcome. (Liver Transpl 2003;9:764-771.)
Independent risk factors and natural history of renal dysfunction in liver transplant recipients
Authors: Pawarode Attaphol , Fine Derek M. , Thuluvath Paul J.
Published: June 2003

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m2 from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m2 for at least 6 months( were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m2 /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m2 were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m2 from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m2 occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients. (Liver Transpl 2003;9:741-747.)
Hepatocellular carcinoma screening in patients waiting for liver transplantation: A decision analytic model
Authors: Saab Sammy , Ly David , Nieto Jose , Kanwal Fasiha , Lu David , Raman Steven , Amado Rafael , Nuesse Barbara , Durazo Francisco , Han Steven , Farmer Douglas G. , Ghobrial Rafik M. , Yersiz Hasan , Chen Pauline , Schwegel Kathy , Goldstein Leonard I. , Tong Myron , Busuttil Ronald W.
Published: June 2003

De novo hepatocellular carcinoma (HCC) may have a large impact on patients waiting for liver transplantation. The presence of HCC can lead to a status upgrade or removal from the waitlist. Our aim is to compare costs and outcomes of different liver cancer surveillance strategies. A Markov-based decision analytic model is created to simulate costs and health outcomes for a hypothetical cohort awaiting liver transplantation undergoing HCC screening. Three strategies of HCC screening are compared with the referent strategy of using alphafetaprotein (AFP) level alone: (1) ultrasound (U/S), (2) AFP plus U/S, and (3) computed tomography (CT). Screening is performed for all strategies at 6-month intervals. Selected tumors are treated locally. Costs and clinical outcomes are discounted. Using baseline assumptions, incremental cost-effectiveness ratios (ICERs) for U/S, U/S plus AFP, and CT are $60,300/life-year saved (LY), $74,000/LY, and $101,100/LY, respectively. The most cost-effective strategy was dependent on the relative costs of each screening modality. U/S screening becomes the dominant strategy when the cost of an AFP test is decreased. Our results show that screening with CT is associated the greatest gain in life expectancy and greatest costs. U/S screening strategy is the preferred screening strategy based on the lowest ICER. Ultimately, costs of the screening modalities determine the most cost-effective strategy. (Liver Transpl 2003;9:672-681.)
Model for End-Stage Liver Disease score does not predict patient or graft survival in living donor liver transplant recipients
Authors: Hayashi Paul H. , Forman Lisa , Steinberg Tracy , Bak Thomas , Wachs Michael , Kugelmas Marcelo , Everson Gregory T. , Kam Igal , Trotter James F.
Published: June 2003

Although living donor liver transplantation (LDLT( is a successful procedure for most recipients, outcomes in patients who undergo transplantation as United Network for Organ Sharing status 2A are marginal. There are no published data on living donor liver transplant recipient outcomes relative to Model for End-Stage Liver Disease (MELD( scores. Such information could be useful in living donor liver transplant recipient selection. We retrospectively analyzed all non-fulminant hepatic failure, right hepatic lobe, adult-to-adult living donor liver transplant recipients at our center between August 1997 and March 2002. We calculated MELD scores at the time of LDLT and correlated scores with 1-year patient and graft survival and hospital days during the 90-day post-LDLT period. There were 62 recipients with greater than 6 months of follow-up: 38 men, 24 women; mean age, 47.9 years; 42 white, 1 black, 17 Hispanic, and 2 Asian patients. Twenty-nine patients had hepatitis C virus infection; 4 patients, hepatitis C virus infection and alcoholic liver disease; 4 patients, alcoholic liver disease; 4 patients, cryptogenic cirrhosis; 13 patients, primary sclerosing cholangitis; 5 patients, autoimmune hepatitis; and 3 patients, primary biliary cirrhosis. Mean and median MELD scores were 15.2 and 13, respectively (range, 6 to 40(. One-year patient and graft survival were 59 of 62 patients (95%( and 52 of 62 patients (84%(, respectively. There was no statistically significant difference between median MELD scores of dead versus living patients (15 v 13; P = .15( or patients who underwent retransplantation versus those who did not (16.5 v 13; P = .30(. Mean and median hospital days in the 90-day post-LDLT period were 23.7 and 16.0 days, respectively. Living donor liver transplant recipients with a MELD score of 18 or greater had significantly more hospital days compared with recipients with a MELD score less than 18 (35.2 v 19.8 days; P = .01(. In conclusion, MELD scores did not predict post-LDLT patient or graft survival at 1 year. However, higher MELD scores (≥18( were associated with more hospital days during the 3-month post-LDLT period. (Liver Transpl 2003;9:737-740.(
The effect of liver graft-body weight ratio on the core temperature of pediatric patients during liver transplantation
Authors: Jawan Bruno , Luk Hsiang-Ning , Chen Yaw-Sen , Wang Chih-Chi , Cheng Yu-Fan , Huang Tung-Liang , Eng Hock-Liew , Liu Po-Ping , Chiu King-Wah , Chen Chao-Long
Published: June 2003

The left lateral segment of the liver from an adult living donor sometimes is relatively too large for a small pediatric recipient. It currently is unknown whether a high graft-recipient body weight ratio (GRWR) has a significant effect on core temperature during the anhepatic and reperfusion phases of living donor liver transplantation (LDLT). Seventy-two pediatric patients undergoing LDLT were divided into two groups according to body weight. Group I (GI) consisted of patients with a body weight greater than 10 kg, and group II (GII), less than 10 kg. Core temperature, measured as nasopharyngeal temperature (NT), was compared between groups at induction of anesthesia, hourly during the following 6 hours, as the lowest core temperature at the anhepatic phase, 5 and 30 minutes after reperfusion, and the last 2 hours before the end of the operation. Mild hypothermia of 35.8°C ± 0.7°C and 35.9°C ± 0.4°C for GI and GII was noted after induction of anesthesia, respectively; this increased ± 1°C in the following 6 hours. In the anhepatic and reperfusion phases, a sudden and significant decrease in NT was observed in both groups. This decrease in NT was significantly greater in GII than GI. In conclusion, a sudden decrease in core temperature was observed during the anhepatic and reperfusion phases of LDLT in pediatric patients, likely caused by placement of the cold liver graft, which is flushed with 4°C lactated Ringer’s solution during vessel reconstruction, in the anhepatic phase and return of venous blood through the cold preserved liver in the reperfusion phase. Core temperatures of pediatric patients with a body weight less than 10 kg in GII, who received grafts with a high GRWR, were more affected than those in GI. (Liver Transpl 2003;9:760-763.)
The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation
Authors: Levitsky Josh , Hart John , Cohen Stanley M. , Te Helen S.
Published: June 2003

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence. Patients who underwent orthotopic liver transplantation (OLT) for PBC were identified from the University of Chicago Liver Transplant Database. Recurrent PBC was diagnosed based on specific pathological criteria. Of 46 patients who underwent OLT for PBC between 1984 and 2000, a total of 7 patients (15%) were diagnosed with recurrent PBC at a median of 78 months (range, 27 to 120 months) after OLT. Forty-three percent of patients were administered cyclosporine, whereas 57% were administered tacrolimus before disease recurrence. Rates of recurrence were not different between patients maintained on cyclosporine therapy (16%) compared with those maintained on tacrolimus therapy (18%; P = 1.0). There also was no difference in frequency of rejection episodes or duration of corticosteroid therapy between those who did and did not have recurrent PBC. In conclusion, recurrent PBC developed in a small number of patients 2 years or longer after OLT. In our population, there was no difference in recurrence rates between those administered cyclosporine or tacrolimus for immunosuppression. (Liver Transpl 2003;9:733-736.)
Predictors of psychiatric disorders in liver transplantation candidates: Logistic regression models
Authors: Rocca Paola , Cocuzza Elena , Rasetti Roberta , Rocca Giuseppe , Zanalda Enrico , Bogetto Filippo
Published: June 2003

This study has two goals. The first goal is to assess the prevalence of psychiatric disorders in orthotopic liver transplantation (OLT) candidates by means of standardized procedures because there has been little research concerning psychiatric problems of potential OLT candidates using standardized instruments. The second goal focuses on identifying predictors of these psychiatric disorders. One hundred sixty-five elective OLT candidates were assessed by our unit. Psychiatric diagnoses were based on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients also were assessed using the Hamilton Depression Rating Scale (HDRS) and the Spielberger Anxiety Index, State and Trait forms (STAI-X1 and STAI-X2). Severity of cirrhosis was assessed by applying Child-Pugh score criteria. Chi-squared and general linear model analysis of variance were used to test the univariate association between patient characteristics and both clinical psychiatric diagnoses and severity of psychiatric diseases. Variables with P less than .10 in univariate analyses were included in multiple regression models. Forty-three percent of patients presented at least one psychiatric diagnosis. Child-Pugh score and previous psychiatric diagnoses were independent significant predictors of depressive disorders. Severity of psychiatric symptoms measured by psychometric scales (HDRS, STAI-X1, and STAI-X2) was associated with Child-Pugh score in the multiple regression model. Our data suggest a high rate of psychiatric disorders, particularly adjustment disorders, in our sample of OLT candidates. Severity of liver disease emerges as the most important variable in predicting severity of psychiatric disorders in these patients. (Liver Transpl 2003;9:721-726.)
Psychological outcome and quality of life following liver transplantation: A prospective, national, single-center study
Authors: O’Carroll Ronan E. , Couston Margaret , Cossar Jill , Masterton George , Hayes Peter Clive
Published: June 2003

Liver transplantation is a well-established treatment for liver failure. Prolongation in survival is accepted, but long-term effects of liver transplantation on cognitive and psychological outcome are unclear. In the present study, psychological data were prospectively collected for 164 patients who were assessed for liver transplantation. Memory impairment, psychomotor slowing, anxiety, and depression were commonly observed. Severity of liver disease at assessment was significantly associated with slowing of reaction time. Memory impairment distinguished those who were not listed for transplantation because of illness severity. One year posttransplantation, follow-up data from transplant recipients showed significant improvement in most psychological domains relative to both healthy comparison participants and patients with chronic liver disease who did not undergo transplantation. Immunosuppression (cyclosporine versus tacrolimus) did not have differential effects on quality of life, fatigue, or affective status, although those administered cyclosporine showed greater improvements at 1-year follow-up on simple and choice reaction times. Elevated levels of anxiety and neuroticism at pretransplantation assessment were associated with worse psychosocial outcome at 1 year posttransplantation. Severity of liver disease was not related to psychological outcome at 1 year. Good psychological outcome at 1 year was maintained at the 3-year follow-up. (Liver Transpl 2003;9:712-720.)
Carriage of methicillin-resistant Staphylococcus aureus is associated with an increased risk of infection after liver transplantation
Authors: Desai Devendra , Desai Nutan , Nightingale Peter , Elliott Tom , Neuberger James
Published: June 2003

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of sepsis in patients with cirrhosis and after liver transplantation. The association between nasal carriage of MRSA and sepsis in these patients is unclear. The goal of this study was to investigate the relationship between MRSA carriage before liver transplantation and subsequent sepsis after transplantation. This was a retrospective study of 374 consecutive adults who underwent orthotopic liver transplantation between 1998 and 2001 and for whom full data were available. Of these, 157 had been screened for MRSA as part of a study assessing the prevalence of MRSA infection. All MRSA carriers were treated with nasal mupirocin and chlorhexidine baths. The records of MRSA carriers and noncarriers were analyzed for Child and Model for End-Stage Liver Disease (MELD) score, posttransplantation MRSA, and other infections and mortality. Of the 157 patients who had an MRSA screen, 35 patients were MRSA nasal carriers. These carriers had significantly greater MELD score (mean, 16.2 compared with 13.1; P = .02) and Child scores (mean, 10 versus 9; P = .001) than noncarriers. The incidence of posttransplantation MRSA infection was significantly higher in MRSA carriers (31% versus 9%; P = .002). The incidence of other posttransplantation infection was not significantly different in the two groups. There was no significant difference in survival between the two groups (1-year patient survival, 74% and 82%, respectively). Patients carrying MRSA are predisposed to an increased risk of sepsis after liver transplantation with a trend to increased mortality. Screening for MRSA should be considered in high-risk patients being assessed for liver transplantation. (Liver Transpl 2003;9:754-759.)
Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation
Authors: Kugelmas Marcelo , Spiegelman Purnima , Osgood Michael J. , Young David A. , Trotter James F. , Steinberg Tracy , Wachs Michael E. , Bak Thomas , Kam Igal , Everson Gregory T.
Published: June 2003

Primary sclerosing cholangitis (PSC) is the fourth leading diagnosis in liver transplant recipients in the United States. The disease is known to recur in 15% to 30% of liver transplant recipients. We set out to investigate how different immunosuppression regimens affected natural history of PSC after liver transplantation at our center. We reviewed records of all patients who underwent a liver transplantation at our institution in between 1988 and 2000 and had a diagnosis of PSC at the time of liver transplantation. Primary sclerosing cholangitis recurred in 15 of 71 patients (21.1%) who had complete records and survived more than 30 days after liver transplantation. Although recurrence of primary sclerosing cholangitis was most often seen (but not statistically significantly so) in patients who received maintenance corticosteroids, the time to recurrence was not significantly different between those who were treated with maintenance, those who were not successfully weaned, and those who successfully weaned off corticosteroids within 3 months after liver transplantation. Orthoclone (OKT3) therapy (Ortho-Biotech, Inc., Raritan, NJ) was associated with a higher risk of primary sclerosing cholangitis recurrence (29% versus 10%, P < .05). Recurrence was not influenced by immunosuppression with either cyclosporine or tacrolimus. Coexistent inflammatory bowel disease was a cause of failure to wean off corticosteroids, was associated with a shorter time to recurrence of sclerosing cholangitis, and was responsible for significant comorbidity (colon cancer in 7.3%). Primary sclerosing cholangitis recurrence is commonly seen after liver transplantation. More immunosuppression seems to be detrimental to the outcome of our patients with sclerosing cholangitis: use of OKT3 was associated with a greater incidence of recurrence. Length of corticosteroid use did not affect timing or risk of recurrence, and because it has been proven that early corticosteroid withdrawal after liver transplantation is beneficial, we continue to recommend this practice. (Liver Transpl 2003;9:727-732.)
Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival
Authors: Marsh Wallis J. , Finkelstein Sydney D. , Demetris Anthony J. , Swalsky Patricia A. , Sasatomi Eizaburo , Bandos Andriy , Subotin Michael , Dvorchik Igor
Published: June 2003

The goal of this study was to determine whether a panel of tumor suppressor gene markers of allelic loss could serve as a representative indicator of gene damage and thereby provide further discriminative power over current staging systems for recurrence-free prognostication in patients undergoing liver transplantation in the presence of hepatocellular carcinoma. The paraffin blocks from 103 cases of hepatocellular carcinoma were obtained, and cellular targets were selected for tissue microdissection genotyping. Tumor suppressor gene loss was based on loss of heterozygosity situated within or adjacent to specific genes of interest (APC, CDKN2A, DCC, MET, MYC1, OGG1, p34, p53, PTEN). Microdissected tissue was amplified using polymerase chain reaction (PCR) with flanking oligonucleotides bearing fluorescent labels designed for GeneScan fragment analysis; PCR products were separated by capillary electrophoresis. Normal microdissected tissue samples for each case were evaluated for informative status with respect to individual alleles for 18 microsatellites at 10 genomic loci—1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q. The measure of allelic loss of heterozygosity combined with tumor number, tumor size, vascular invasion, lobar distribution, and patient gender provide a highly discriminatory model for predicting cancer recurrence after liver transplantation. Using our previously developed artificial neural network model in combination with the genotyping results, unambiguous predictions were made for 91 of the103 patients (88.3%). Of these, 1 was lost to follow-up, and 9 died recurrence-free less than 3 years posttransplantation. For the remaining 81, the combined models predicted tumor recurrence outcomes with complete accuracy. Microdissection genotyping provides powerful supplementary discriminative information for tumor-free survival. (Liver Transpl 2003;9:664-671.)
A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: Implications for the current organ allocation policy
Authors: Yao Francis Y. , Bass Nathan M. , Nikolai Bev , Merriman Raphael , Davern Timothy J. , Kerlan Robert , Ascher Nancy L. , Roberts John P.
Published: June 2003

Since our interim report of the intention-to-treat outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), we have performed a follow-up analysis of an expanded cohort of 70 patients to further assess whether the observed pattern and predictors of dropout are consistent with the rationale behind current HCC-adjusted Model for End Stage Liver Disease (MELD) organ allocation scheme. All except one patient had pretransplantation staging meeting our proposed expanded criteria—a single lesion ≤6.5 cm, or three or fewer lesions none >4.5 cm and total tumor diameter ≤8 cm. Thirty-eight patients received OLT. The cumulative probabilities of dropout at 6, 12, and 18 months were 7.2%, 37.8%, and 55.1%, respectively. The respective dropout probabilities would have been 11.0%, 57.4%, and 68.7% if the United Network for Organ Sharing (UNOS) criteria for exclusion (single lesion ≤5 cm or three or fewer lesions none >3 cm) were applied. Predictors of dropout with either criteria included three tumor nodules and a single lesion >3 cm at initial presentation, whereas preoperative chemoembolization or ablation therapies were associated with a lower risk for dropout only when applying the UNOS criteria for patient exclusion. In the subgroup with two or three lesions or a solitary tumor >3 cm, the cumulative probabilities of dropout were nine-fold higher than those with a single lesion ≤3cm (P = .004). In conclusion, the low dropout rate in the first 6 months and the differing dropout risks based on tumor characteristics support further refinements in the HCC-adjusted MELD organ allocation scheme. (Liver Transpl 2003;9:684-692.)
Longitudinal prospective evaluation of quality of life in adult patients before and one year after liver transplantation
Authors: Karam Vincent , Castaing Denis , Danet Colette , Delvart Valérie , Gasquet Isabelle , Adam René , Azoulay Daniel , Samuel Didier , Bismuth Henri
Published: June 2003

We assessed the impact of liver transplantation (LT) on the quality of life (QOL) of French recipients 1 year after surgery. A French version of the questionnaire used by the National Institute of Diabetes and Digestive and Kidney Disease—Pittsburg, USA (NIDDK), was validated by the back-translation method. Five QOL domains were evaluated: measures of disease, psychological distress, personal function, social function, and general health perception. Patients enrolled onto the waiting list completed the questionnaire before and 1 year after LT. Respondents were age- and gender-matched with healthy subjects recruited from the general population (GP). One year after LT, the analysis of data from 67 consecutive patients showed dramatic improvement in the five domains. Compared with baseline, patients noted fewer disease-related symptoms (P < .0001) and lower level of distress overall (P < .001). However, levels of distress caused by excess appetite (P < .01), trembling (P < .05), and headaches (P = .06) were more likely to increase than decrease. Twenty-five percent of patients prevented by their disease from going to work before LT were no longer so limited at 1-year follow-up. General health perception improved remarkably, with seven times as many recipients reporting improved health as reporting worse health. A correlation was found between the pretransplantation severity of cirrhosis and the social and role function after LT (P < .05). In summary, the French version of the NIDDK questionnaire seems to be reliable. The results of transplant recipients were generally close to those of the general population. Although it is not a true return to normal status, it approaches it. (Liver Transpl 2003;9:703-711.)
First report of a psychosocial intervention for patients with alcohol-related liver disease undergoing liver transplantation
Authors: Georgiou George , Webb Kerry , Griggs Karen , Copello Alex , Neuberger James , Day Ed
Published: June 2003

Performing transplantations in patients with alcoholic liver disease raises great concerns for both clinicians and lay people, not least because of the fear that relapse back to drinking after the procedure may lead to poor outcomes. Therefore it is important to develop and evaluate new strategies for assessing and supporting such patients. A program of psychosocial intervention was developed to assist patients undergoing transplantation for alcoholic liver disease in coping with their alcohol problems. We describe a feasibility study of its implementation in a group of 20 such patients. This report shows that it is feasible to deliver a time-limited psychological intervention to patients undergoing assessment for liver transplantation. The intervention was readily integrated into the usual transplantation process and was acceptable to both patients and staff. Further research is required to clarify its impact on longer-term outcome measures. (Liver Transpl 2003;9:772-775.)
A multistep mechanism for the activation of rearrangement in the immune system
Authors: Ji Yanhong , Zhang Jianmin , Lee Alfred Ian , Cedar Howard , Bergman Yehudit
Published: June 2003

Rearrangement of immune receptor loci is a developmentally controlled process that takes place exclusively in lymphoid cells. We have used a stable transfection system in pre-B cells to show that DNA methylation brings about histone underacetylation, histone H3(K9) methylation, DNaseI resistance, and strong inhibition of both transcription and recombination. Strikingly, this repression is maintained in dividing cells even after removal of the original methyl groups responsible for its establishment, but in this state, rearrangement can now be induced by reacetylation of local histones using the drug Trichostatin A. This same combination of demethylation and histone acetylation is also required to activate germline transcription and recombination from the endogenous κ locus
in vivo
. These results indicate that the regulation of rearrangement is carried out by a multilayered synergistic process.
Gene function analysis in environmental isolates: The
nif
regulon of the strict iron oxidizing bacterium
Leptospirillum ferrooxidans
Authors: Parro Víctor , Moreno-Paz Mercedes
Published: June 2003

A random genomic library from an environmental isolate of the Gram-negative bacterium
Leptospirillum ferrooxidans
has been printed on a microarray. Gene expression analysis was carried out with total RNA extracted from
L. ferrooxidans
cultures in the presence or absence of ammonium as nitrogen source under aerobic conditions. Although practically nothing is known about the genome sequence of this bacterium, this approach allowed us the selection and sequencing of only those clones bearing genes that showed an altered expression pattern. By sequence comparison, we have identified most of the genes of nitrogen fixation regulon in
L. ferrooxidans
, like the
nifHDKENX
operon, encoding the structural components of Mo-Fe nitrogenase;
nifSU-hesB-hscBA-fdx
operon, for Fe-S cluster assembly; the
amtB
gene (ammonium transporter);
modA
(molybdenum ABC type transporter); some regulatory genes like
ntrC, nifA
(the specific activator of
nif
genes); or two
glnB
-like genes (encoding the PII regulatory protein). Our results show that shotgun DNA microarrays are very powerful tools to accomplish gene expression studies with environmental bacteria whose genome sequence is still unknown, avoiding the time and effort necessary for whole genome sequencing projects.
Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase that can regulate cell survival and proliferation
Authors: Oganesian A. , Poot M. , Daum G. , Coats S. A. , Wright M. B. , Seifert R. A. , Bowen-Pope D. F.
Published: June 2003

Protein tyrosine phosphatase RQ (PTPRQ) was initially identified as a protein tyrosine phosphatase (PTPase)-like protein that is upregulated in a model of renal injury. Here we present evidence that, like PTEN, the biologically important enzymatic activity of PTPRQ is as a phosphatidylinositol phosphatase (PIPase). The PIPase specificity of PTPRQ is broader than that of PTEN and depends on different amino acid residues in the catalytic domain.
In vitro
, the recombinant catalytic domain of PTPRQ has low PTPase activity against tyrosine-phosphorylated peptide and protein substrates but can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. PTPRQ does not have either of the basic amino acids in the catalytic domain that are important for the PIPase activity of PTEN or the sequence motifs that are characteristic of type II phosphatidylinositol 5-phosphatases. Instead, the PIPase activity depends on the WPE sequence present in the catalytic cleft of PTPRQ, and in the ``inactive'' D2 domains of many dual-domain PTPases, in place of the WPD motif present in standard active PTPases. Overexpression of PTPRQ in cultured cells inhibits proliferation and induces apoptosis. An E2171D mutation that retains or increases PTPase activity but eliminates PIPase activity, eliminates the inhibitory effects on proliferation and apoptosis. These results indicate that PTPRQ represents a subtype of the PTPases whose biological activities result from its PIPase activity rather than its PTPase activity.
Twisted group rings of metacyclic groups
Authors: Quinlan Rachel
Published: June 2003

Given a finite metacyclic group

G
G

, a central extension

F
F

having the projective lifting property over all fields is constructed. This extension and its group rings are used to investigate the faithful irreducible projective representations of

G
G

and the fields over which they can be realized. A full description of the finite metacyclic groups having central simple twisted group rings over fields is given.
Current issues in marketing organic milk in the UK
Authors: Franks Jeremy
Published: June 2003

The recent background to the UK market for organic milk is reviewed to establish the background to the Organic Dairy Production: A Sustainable Future for Organic Dairying conference held in March 2002. The presentations given at that conference are critically reviewed. Several of arguably the most important determinants of the sustainable future of organic dairying did not find their full expression at that conference. Issues largely or wholly excluded include: a priori evidence for expecting a higher level of co‐operation among organic than conventional farmers; the distinction between “competitive pricing” and “sustainable pricing”; import penetration and substitution, and post‐conversion subsidies; utilising innovative information technologies to “tell the organic story”; policing organic standards and traceability; and the ownership of the “organic label” and the number of organic standard bodies. The importance of these issues is shown by reference to the current market situation for organic milk in the UK. There is a need for considerable developments in the marketing of organic milk. More distance must be placed between associations that campaign for market growth and an organisation that will need to be appointed to take responsibility for providing reliable and impartial market‐based information.
Using e‐learning to liberate the talents of nurses
Authors: Young Kevin
Published: June 2003

Gives an overview of the way the National Health Service (NHS) approached the implementation of e‐learning to provide leadership training to 40,000 nurses. The project provided training to clinical staff at a cost of less than 50p per nurse and became one of the very few e‐learning programmes to deliver audio, graphics and text in real‐time over a 56K modem. Explains how – instead of investing heavily in creating bespoke e‐learning from scratch – the NHS team achieved a highly effective customised solution using generic e‐learning content and adapting it to the hospital environment. The project has been highly acclaimed and, in February 2003, it won the top award for “e‐learning project of the year” at the IT Training Awards. Details the various phases through which the NHS went to achieve this award‐winning success.
Centrica uses skills management from John Matchett Limited
Authors: Hague John
Published: June 2003

This article outlines how Centrica, with a workforce of 40,000 people, approached a project to build a technical competence framework for the managers of Centrica’s group financial operation in 2001. Development took six months and 600 employees were involved. As well as John Matchett Limited which provided the system, consultants Moloney and Gealy were used in the later stage of development to refine the competence headings, descriptors and language into its present form. At first there were problems with the online systems but Centrica’s IT systems were modified and the problems were overcome. The system is constantly being improved, particularly in the links to learning and development opportunities, and the use of technical competences will be strengthened in initial recruitment to group finance vacancies. The whole competency concept has taken off at Centrica and, taking their lead from group finance, the marketing, legal and HR functions are all putting their own frameworks in place.
Implementation of computer‐integrated manufacturing in small and medium enterprises
Authors: Marri H.B. , Gunasekaran A. , Kobu Bulent
Published: June 2003

The revolution in information technology and the changes in political and social environments during the last two decades have created a very competitive global market. In order to remain competitive, business organizations have focused on innovative techniques for product and process designs. Owing to limited resources, small and medium enterprises (SMEs) need to work harder than large corporations in order to survive in a situation of ever‐increasing competition. Considering the importance of elements of computer‐integrated manufacturing (CIM), a framework for the implementation of CIM in SMEs has been developed with the help of a survey conducted in a randomly selected group of 24 SMEs. Also highlights the issues of human resource in the implementation of CIM in SMEs. Finally, presents future research directions.