bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and virologic outcomes of hepatitis B and C viral coinfection after liver transplantation: Effect of viral hepatitis D
Authors: Taniguchi Makoto , Shakil Obaid A. , Vargas Hugo E. , Laskus Tomasz , Demetris Anthony J. , Gayowski Timothy , Dodson Forrest S. , Fung John J. , Rakela Jorge
Published: July 2004

Hepatitis B (HBV) and C viral (HCV) dual-infection-associated liver disease is an uncommon indication for liver transplantation. The clinical and virologic outcomes in such patients have not been well studied. We retrospectively studied 13 patients with hepatitis B surface antigen (HBsAg) and antibody to HCV positivity who underwent orthotopic liver transplantation (OLT) and survived at least 30 days post-OLT. Antibody to hepatitis delta virus (HDV) was negative in 8 patients (group I) and positive in 5 patients (group II). Eleven of the 13 patients received standard hepatitis B immune prophylaxis, and they all remained HBsAg negative. All group I patients were HCV RNA positive after transplantation; in contrast, all group II patients were HCV RNA negative. Serum alanine aminotransferase levels were elevated in 88% (7 of 8) of the patients in group I compared with 20% (1 of 5 patients) in group II. None of the patients had graft loss from chronic rejection or recurrent hepatitis. Three patients had unsuspected hepatocellular carcinoma in the explant. We conclude that among liver transplant recipients with HBV and HCV coinfection, HDV infection is associated with the suppression of HCV replication and mild inflammatory activity after OLT.
Prediction of liver allograft fibrosis after transplantation for hepatitis C virus: Persistent elevation of serum transaminase levels versus necroinflammatory activity
Authors: Pelletier Shawn J. , Iezzoni Julia C. , Crabtree Traves D. , Hahn Young S. , Sawyer Robert G. , Pruett Timothy L.
Published: July 2004

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) remains a significant source of morbidity and mortality. Factors that reliably predict allograft injury from HCV have not been identified. Demographics, clinical data, and histopathological characteristics of recipients with and without persistently elevated serum transaminase levels (PEST) were compared. Twenty-four patients with HCV-induced end-stage liver disease who underwent OLT between October 1995 and December 1998 were entered into a longitudinal, prospective evaluation for identification of parameters associated with graft injury. Liver biopsies were performed preoperatively and between posttransplantation days 1 to 28, 29 to 60, 61 to 180, 181 to 360, and then every 6 to 12 months thereafter. Biopsy specimens were reviewed in a blinded fashion and scored for rejection, necroinflammatory activity, extent of fibrosis, and infiltrating cell type, location, and magnitude. Transplant recipients with PEST (alanine transaminase level >1.5 times normal for 3 consecutive months) and cholestatic hepatitis showed an increased viral load compared with their own preoperative values (16-fold and 256-fold, respectively). Compared with control transplant recipients, PEST was associated with macrovesicular steatosis within 28 days after OLT (P < .05) and showed an increased rate of fibrosis (P < .003) despite similar degrees of rejection and necroinflammatory activity. There was no difference in demographics or immunosuppression. Macrovesicular steatosis may be the earliest predictor of graft fibrosis. Despite similar degrees of necroinflammatory activity, transplant recipients with PEST had an increased rate of fibrosis that could be predicted on average within 6 months posttransplantation.

(Liver Transpl 2000;6:44-53.)
Predicting bacteremia and bacteremic mortality in liver transplant recipients
Authors: Singh Nina , Paterson David L. , Gayowski Timothy , Wagener Marilyn M. , Marino Ignazio R.
Published: July 2004

Predictors of bacteremia and mortality in bacteremic liver transplant recipients were prospectively assessed. One hundred eleven consecutive episodes of fever or infections were documented in 59 patients over a 4-year period. Forty-nine percent (29 of 59 patients) of the patients had bacteremia, 39% (23 of 59 patients) had nonbacteremic infections, and 12% (7 of 59 patients) had fever of noninfectious cause. Primary (catheter-related) bacteremia (31%; 9 of 29 patients), pneumonia (24%; 7 of 29 patients), abdominal and/or biliary infections (14%; 4 of 29 patients), and wound infections (10%; 3 of 29 patients) were the predominant sources of bacteremia. Diabetes mellitus (odds ratio, 6.9; P = .03) and serum albumin level less than 3.0 mg/dL (odds ratio, 0.14; P = .02) were independently significant predictors of bacteremia compared with nonbacteremic infections. Mortality at 14 days was 28% (8 of 29 patients) in those with bacteremia compared with 4% (1 of 23 patients) in those with nonbacteremic infections and 0% (0 of 7) in patients with fever of noninfectious cause (P = .03). Intensive care unit stay at the time of bacteremia (100% v 47%; P = .005), absence of chills (0% v 53%; P = .005), lower temperature at the onset of bacteremia (99.2°F v 101.5°F; P = .009), lower maximum temperature during the course of bacteremia (99.3°F v 102°F, P = .008), greater serum bilirubin level (7.6 v 1.5 mg/dL;P = .024), presence of abnormal blood pressure (80% v16%; P = .0013), and greater prothrombin time (15.6v 13.3 seconds; P = .013) were significantly predictive of greater mortality in the bacteremic patients. These data have implications for discerning the likelihood of bacteremia and initiation of empiric antibiotics pending cultures. Lack of febrile response in bacteremic liver transplant recipients portended a poorer outcome.

(Liver Transpl 2000;6:54-61.)
Hepatic resection of noncolorectal nonneuroendocrine metastases
Authors: Hemming Alan W. , Sielaff Tim D. , Gallinger Steven , Cattral Mark S. , Taylor Bryce R. , Greig Paul D. , Langer Bernard
Published: July 2004

Because hepatic resection is generally a safe procedure, the indications for resection of noncolorectal nonneuroendocrine (NCNNE) hepatic metastases have broadened. The prognostic features of NCNNE metastases treated surgically were reviewed to define better the value of resection. A retrospective review of patients undergoing liver resection for NCNNE metastases between 1978 and 1998 was undertaken. Thirty-seven patients were identified. Mean age was 56 years, with a median follow-up of 22 months. Primary tumor sites were grouped into gastrointestinal (GI) adenocarcinoma (small bowel, n = 4; pancreas, n = 2; esophagus, n = 1) and other (renal cell, n = 7; sarcoma, n = 7; melanoma, n = 5; adrenal, n = 3; unknown adenocarcinoma, n = 3; thyroid, n = 2; testicular, n = 1; ovarian, n = 1; breast, n = 1). All patients underwent surgery for cure. Metastases were synchronous in 14 patients. There was no surgical mortality. Overall 5-year survival rate was 45%. Five-year survival rates were better for patients with non-GI-origin metastases (60%v 0%; P = .01). Long-term survival was seen only in patients with non-GI-origin metastases. The extent of resection, presence of synchronous metastases, or disease-free interval from time of original disease to presentation with liver metastases were not predictive of outcome. We conclude that patients with NCNNE hepatic metastases can undergo liver resection with an expectation of prolonged survival. However, patients with liver metastases from GI primary tumors other than the colorectum are unlikely to show extended survival.
Clinical predictors of pulmonary hypertension in patients undergoing liver transplant evaluation
Authors: Pilatis Nektarios D. , Jacobs Larry E. , Rerkpattanapipat Pairoj , Kotler Morris N. , Owen Alyson , Manzarbeitia Cosme , Reich David , Rothstein Kenneth , Munoz Santiago J.
Published: July 2004

Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P < .001), (2) loud pulmonary component of the second heart sound (38% v 2%; P = .001), (3) right ventricular (RV) heave (38% v 4%; P = .002), (4) RV dilatation by echocardiogram (63% v 0%; P < .001), (5) RV hypertrophy by echocardiogram (38% v 0%; P = .001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P < .001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.
Liver transplantation
Authors: Carithers Robert L.
Published: July 2004

Liver transplantation has revolutionized the care of patients with end-stage liver disease. Liver transplantation is indicated for acute or chronic liver failure from any cause. Because there are no randomized controlled trials of liver transplantation versus no therapy, the efficacy of this surgery is best assessed by carefully comparing postoperative survival with the known natural history of the disease in question. The best examples of this are in primary biliary cirrhosis and primary sclerosing cholangitis, for which well-validated disease-specific models of natural history are available. There are currently relatively few absolute contraindications to liver transplantation. These include severe cardiopulmonary disease, uncontrolled systemic infection, extrahepatic malignancy, severe psychiatric or neurological disorders, and absence of a viable splanchnic venous inflow system. One of the most frequently encountered contraindications to transplantation is ongoing destructive behavior caused by drug and alcohol addiction. The timing of the surgery can have a profound impact on the mortality and morbidity of patients undergoing liver transplantation. Because of the long waiting lists for donor organs, the need to project far in advance when transplantation might be required has proven to be one of the greatest challenges to those treating patients with end-stage liver disease. Three important questions must be addressed in a patient being considered for liver transplantation: (1) when should the patient be referred for possible transplantation? (2) when should the patient be listed for transplantation? and (3) when is the patient too sick to have a reasonable chance of surviving the perioperative period?
Increased late hepatic artery thrombosis rate and decreased graft survival after liver transplants with zero cross-reactive group mismatches
Authors: Sawyer Robert G. , Pelletier Shawn J. , Spencer Clint E. , Pruett Timothy L. , Isaacs Ross B.
Published: July 2004

The use of broad-specificity cross-reactive groups (CREGs) at the A and B HLA loci has been proposed as a means to improve both access and outcome for renal transplantation but has not yet been studied for liver transplantation. We retrospectively analyzed our results for all adult liver transplantations performed at our center between 1989 and 1996 for which HLA typing and complete 3-year follow-up data were available. Two hundred eight transplantations were studied, with a mean follow-up of 66 ± 2 months (range, 36 to 110 months); A and B loci were converted to CREGs by the method of Rodey. Thirteen percent of the patients with 0 CREG mismatches had hepatic artery thrombosis versus 2% for those with 1 or more mismatches (odds ratio, 6.7; 95% confidence interval, 2.6 to 17.3 by univariate analysis; odds ratio, 3.5; 95% confidence interval, 1.1 to 11.7 by logistic regression analysis). These events occurred significantly later in the 0-CREG mismatch group (21 ± 7 v 4 ± 2 months posttransplantation; P = .04 by Student’s t-test). Graft survival rates were significantly lower for patients with 0 CREG mismatches (56% v 68% at end of study; P = .05 by Cox-Mantel test). The number of CREG mismatches had no effect on the frequency of rejection, steroid-resistant rejection, or infectious complications, including cytomegalovirus. Neither total nor individual A, B, or DR HLA matching had an effect on outcome. There appears to be little evidence that intentional CREG matching would improve outcomes for liver transplantation and, under some circumstances, could be deleterious.
Transplantation of three adult patients with one cadaveric graft: Wait or innovate
Authors: Azoulay Daniel , Castaing Denis , Adam René , Mimoz Olivier , Bismuth Henri
Published: July 2004

Graft shortage continues to prolong waiting times for adults requiring liver transplantation. Living related donor transplantation is possible for only a small minority of adults. The techniques for in situ splitting of the liver used for right and left hepatectomies in living donors were adapted to a combined split-liver-domino procedure to obtain right and left hemiliver grafts from a patient undergoing total hepatectomy with liver transplantation for a metabolic disorder. The two grafts were adequate in size and function for transplantation to two adults with low priority for regular cadaver grafts. More frequent use of split-liver techniques in cadaver donors could considerably reduce the graft shortage and waiting time for adult liver recipients.
Rapid method for the analysis of peripheral chimerism in suspected graft-versus-host disease after liver transplantation
Authors: Hahn Amy B. , Baliga Prabhakar
Published: July 2004

The effects of microchimerism and possible tolerance have been well studied in orthotopic liver transplantation. In some patients, greater levels of donor cells persist in the periphery. These cells were characterized and their effects on clinical outcome were studied. Peripheral blood was obtained from patients at various times posttransplantation. HLA class II typing was performed by the polymerase chain reaction-sequence-specific primer method on unfractionated blood and lymphocyte subpopulations. Relative levels of amplification of donor and recipient alleles were compared. All patients studied had a low degree of chimerism that was most apparent in the CD8+T/natural killer (NK) cell population. One patient with persistently high levels of donor alleles in his CD8+T/NK cell population was diagnosed with severe graft-versus-host disease (GVHD) and died of opportunistic infections. Another patient with biopsy-proven GVHD was chimeric in several cell populations. On resolution of her symptoms, donor alleles were reduced to levels undetectable by this assay. These results suggest that persistently elevated levels of donor CD8+T/NK cells in the periphery may indicate GVHD in liver transplant recipients. This technique aids in rapid diagnosis, which facilitates appropriate treatment and thus may improve clinical outcome.
Results of choledochojejunostomy in the treatment of biliary complications after liver transplantation in the era of nonsurgical therapies
Authors: Davidson Brian R. , Rai Rakesh , Nandy Ashim , Doctor Nilesh , Burroughs Andrew , Rolles Keith
Published: July 2004

Advances in radiological and endoscopic techniques have allowed many biliary complications after orthotopic liver transplantation (OLT) to be managed without surgery. The influence of nonsurgical management on the outcome of patients requiring surgical revision has not been addressed. We reviewed our 10-year experience (October 1988 to January 1998) of Roux-en-Y choledochojejunostomy (CDJ) to treat biliary complications after OLT. Forty-six patients underwent CDJ for biliary complications (32 men, 14 women; age, 22 to 65 years; median, 60 years). Biliary reconstruction at the time of OLT was duct to duct in 41 patients, primary CDJ in 3 patients, and gall bladder conduit in 2 patients. T-tubes were used only in patients with gallbladder conduit. The indication for CDJ was biliary leak (23 patients), stricture (20 patients), biliary stones (2 patients), and biliary sludge (1 patient). Two patients (4.3%) had associated hepatic artery thrombosis. The bile leaks were diagnosed at a median of 29 days post-OLT (range, 2 to 65 days) and strictures at a median of 2 years (range, 33 days to 6.5 years) post-OLT. Before surgery, 25 patients (54%) underwent an attempt at radiological or endoscopic therapeutic intervention that failed. Median follow-up was 5 years (range, 9 months to 10 years). Early complications occurred in 12 patients (26%); the most common was chest infection (4 patients). There were 3 perioperative deaths (6%); 1 death was directly related to surgery. Late complications, mainly anastomotic strictures, occurred in 10 patients (22%), half of which were successfully treated by biliary balloon dilatation. The complication rate post-CDJ was less in those who underwent a failed nonsurgical approach than those proceeding straight to surgery (9 of 25 patients; 36% v 13 of 21 patients; 62%; P = .21, not significant). The procedure-related mortality for surgical revision of biliary complications after OLT is low, but early and late complications are common. A failed attempt at nonsurgical management does not increase the complications of reconstructive surgery. Strictures after CDJ should be considered for biliary balloon dilatation.
Adenosine A2 receptor stimulation protects the predamaged liver from cold preservation through activation of cyclic adenosine monophosphate-protein kinase a pathway
Authors: Minor Thomas , Akbar Susanne , Yamamoto Yuzo
Published: July 2004

The shortage of organ donors has led to reconsideration for the use of non-heart-beating donors (NHBDs). However, graft injury caused by warm ischemia in livers from NHBDs strongly affects posttransplantation outcome. The aim of the present study is to investigate the role of adenosine A2 receptor with regard to hepatic viability after cold preservation of NHBD livers. Cardiac arrest was induced in Wistar rats by phrenotomy of the anesthetized nonheparinized animal. After 60 minutes, the livers were excised and flushed with 60 mL of histidine-tryptophan-ketoglutarate (HTK) and stored submerged in HTK at 4°C for 24 hours. Reperfusion was performed in vitro after all livers were incubated at 22°C in saline solution to account for the period of slow rewarming during surgical implantation in vivo. Addition of the selective A2-receptor agonist (CGS 21680; 30μg/100 mL) to the preservation solution resulted in a significant reduction to one quarter of the parenchymal enzyme release of alanine aminotransferase or lactate dehydrogenase on reperfusion and promoted a 2-fold increase in hepatic bile production. This salutory effect was accompanied by a significant increase (40%) in the activity ratio of protein kinase A (PKA) in the liver tissue and could be abrogated in large part by the PKA inhibitor, Rp-cAMPs. Stimulation of the adenosine A2 receptor during harvest and storage of the graft improves maintenance of tissue integrity in liver grafts. A major part of this effect, which may represent a promising approach for the use of NHBD grafts, seems to be mediated through activation of PKA.
Ascites after liver transplantation
Authors: Cirera Isabel , Navasa Miguel , Rimola Antoni , García-Pagán Juan Carlos , Grande Luis , Garcia-Valdecasas Juan Carlos , Fuster Josep , Bosch Jaime , Rodes Juan
Published: July 2004

Massive ascites after liver transplantation, although uncommon, usually represents a serious adverse event. The pathogenesis of this complication has not been adequately investigated. To determine the incidence, characteristics, and pathogenic factors of massive ascites after liver transplantation (ascitic fluid > 500 mL/d for >10 days), the charts of 378 liver transplant recipients were reviewed. Massive ascites occurred in 25 patients (7%). Mean ascitic fluid production was 960 mL/d (range, 625 to 2,350 mL/d), and the duration of ascites was 77 days (range, 15 to 223 days). The ascitic fluid had a high protein content (36 ± 7 g/L; range, 25 to 50 g/L). When patients who did and did not develop massive ascites were compared, significant differences were found in receptor sex (men, 88% v 60%, respectively; P < .01) and surgical technique (inferior vena cava preservation with piggyback technique, 72% v 41%P < .01). Significantly increased wedged and free hepatic venous pressures and gradients between hepatic vein and right atrial pressures were found in patients who developed ascites, suggesting a difficulty in graft blood outflow. Massive ascites was associated with renal impairment, increased incidence of abdominal infection, prolonged hospitalization, and a tendency toward reduced survival. In conclusion, massive ascites after liver transplantation is relatively uncommon but associated with increased morbidity and mortality and is predominantly related to difficulties of hepatic venous drainage. Measurement of hepatic vein and atrial pressures to detect a significant gradient and correct possible alterations in hepatic vein outflow should be the first approach in the management of these patients.
Retransplantation for late liver graft failure: Predictors of mortality
Authors: Facciuto Marcelo , Heidt David , Guarrera James , Bodian Carol A. , Miller Charles M. , Emre Sukru , Guy Stephen R. , Fishbein Thomas M. , Schwartz Myron E. , Sheiner Patricia A.
Published: July 2004

As patient survival after orthotopic liver transplantation (OLT) improves, late complications, including late graft failure, more commonly occur and retransplantation (re-OLT) is required more often. Survival after re-OLT is poorer than after primary OLT, and given the organ shortage, it is essential that we optimize our use of scarce donor livers. We sought to identify variables that predict poor outcome after late re-OLT. Among adults who underwent OLT between September 1989 and October 1997, we identified transplant recipients who survived greater than 6 months (n = 964) and analyzed those who required late re-OLT (≥6 months after primary OLT). We recorded the indication for the initial OLT and interval from OLT to re-OLT. We also analyzed data collected at the time of re-OLT, including age, sex, indications for primary OLT and re-OLT, United Network for Organ Sharing status, preoperative laboratory values (white blood cells, platelets, hemoglobin, albumin, bilirubin, creatinine, and prothrombin time), Child-Pugh-Turcotte score, number of rejection episodes before re-OLT, and interval between OLT and re-OLT. In addition, we analyzed surgical factors (including procedure performed and use of packed red blood cells, fresh frozen plasma, and platelets), postoperative immunosuppression, and donor factors (age, ischemic time). Forty-eight patients (5%) underwent late re-OLT at a median of 557 days (range, 195 to 2,559 days) post-OLT. Survival rates after re-OLT at 90 days, 1 year, and 5 years were 71%, 60%, and 42%, respectively. Patients surviving 90 days or greater after re-OLT had an 85% chance of surviving to 1 year. Sepsis was the leading cause of death (15 of 25 deaths; 60%). Recipient age older than 50 years (P = .04), preoperative creatinine level greater than 2 mg/dL (P = .004), and use of intraoperative blood products (packed red blood cells, P = .001; fresh frozen plasma, P = .002; platelets, P = .004) had significant impacts on survival. Late re-OLT was associated with increased mortality. Careful patient selection, with particular attention to recipient age and renal function, may help improve results and optimize our use of scarce donor livers.
Prevalence of hepatitis C virus-associated mixed cryoglobulinemia after liver transplantation
Authors: Abrahamian Gregory A. , Cosimi Benedict A. , Farrell Mary Lin , Schoenfeld David A. , Chung Raymond T. , Pascual Manuel
Published: July 2004

Hepatitis C virus (HCV) infection is associated with mixed cryoglobulinemia and membranoproliferative glomerulonephritis. After orthotopic liver transplantation (OLT), isolated cases of HCV-associated mixed cryoglobulinemia have been reported. We determined the prevalence and clinical characteristics of mixed cryoglobulinemia in HCV-infected liver transplant recipients at our institution. Between January 1991 and February 1998, a total of 191 OLTs were performed in 178 patients. Among these transplant recipients, 53 patients (29.8%) had positive serological test results for HCV infection by second-generation enzyme-linked immunosorbent assay. We studied 31 HCV-positive (HCV+) and 21 HCV-negative (HCV-) transplant recipients (control group). Renal and liver function studies were performed, and cryoglobulin, rheumatoid factor, C3, C4, and serum HCV RNA levels and genotype were determined. Results were compared using unpaired Student’t-test for continuous variables and Fisher’s exact test for categorical variables. Baseline characteristics were similar between the groups. Six patients in the HCV+ group (19%) had mixed cryoglobulins present at the time of evaluation compared with none in the HCV- group (P = .036). The only parameter associated with cryoglobulins in the HCV+ group was rheumatoid factor (P< .01). In 3 HCV+ patients with cryoglobulins, extrarenal signs of cryoglobulinemia were present. Glomerulonephritis was found in 4 HCV+ patients. Two patients with purpura and cryoglobulinemia had reduced clinical manifestations after antiviral therapy. In conclusion, mixed cryoglobulinemia was found in approximately 20% of the HCV+ liver transplant recipients. The presence of purpura or glomerulonephritis suggests HCV-associated mixed cryoglobulinemia, a clinical syndrome that may respond favorably to antiviral therapy.
Fetal microchimerisms in the mother: Immunologic implications
Authors: Tanaka Atsushi , Lindor Keith , Ansari Aftab , Gershwin Eric M.
Published: July 2004

The previously held concept that the fetus is completely separated from the mother, especially by trophoblasts that line the outer layer of the placenta, has recently been questioned. It has recently been shown that fetal cells are detectable not only in the peripheral blood, but also in maternal skin and liver. Although the migration of fetal cells into the maternal circulation has been given a great deal of attention because of its implication in the prenatal diagnosis of genetic diseases, the potential role of such placental transfer of fetal cells in the pathogenesis of autoimmune diseases has only recently been considered. In patients with scleroderma, fetal cell-derived DNA was detected more frequently in the peripheral blood of patients than controls. This finding of a limited number of fetal cells in maternal tissues leading to microchimerism has been proposed to have a role in the induction of scleroderma. Although evidence for microchimerism has also been confirmed in a high frequency of liver tissues from patients with primary biliary cirrhosis (PBC), a similar high frequency was noted in control patients, which suggests that microchimerism by itself is unlikely to fully account for the pathogenesis of PBC. The finding of such a high frequency of fetal microchimerism in the liver suggests that this is a very common event, raising the possibility that the migration of fetal cells may be important in the induction and subsequent maintenance of tolerance against the fetus during pregnancy. In addition, it is clearly possible that such microchimerism could contribute to the pathogenesis of select autoimmune diseases.
Relating disease and predation: equilibria of an epidemic model
Authors: Delgado Manuel , Molina‐Becerra Mónica , Suárez Antonio
Published: July 2004

In this paper, we would like compare the spread of an infectious disease in a population without the influence of a predator and under its influence. We show that it is possible to control an epidemic in a population with the help of predators. Copyright © 2004 John Wiley & Sons, Ltd.
Blood γδ T cells, Campylobacter jejuni, and GM1 titers in Guillain–Barré syndrome
Authors: Scelsa Stephen N. , Ghali Violette , Herskovitz Steven , Bieri Phyllis , Shank Deborah L. , MacGowan Daniel D. J. , Liau Sally
Published: July 2004

The γδ T cells participate in microbial defense, are prevalent in intestinal epithelia, and are activated in autoimmune diseases. We studied whether peripheral blood γδ cells and γδ subsets are increased in Guillain–Barré syndrome (GBS) and whether elevations are associated with Campylobacter jejuni infection or GM1 elevations. In 20 GBS patients, we performed serial flow cytometry studies of blood γδ, Vδ1, and Vδ2 cells (±CD8+), C jejuni, and ganglioside titers. There was no significant difference in median γδ T‐cell percentages between GBS patients and controls at onset and at convalescence. However, 5 patients had marked Vδ1/CD8+ elevations. Elevated Vδ1 or Vδ1/CD8+ cells occurred in 3 of 6 patients with C jejuni or GM1 titer elevations. A minority of GBS patients have elevations of Vδ1/CD8+ cells, possibly associated with elevated C jejuni or GM1 titers. The γδ T cells may have a cytotoxic (or suppressor) role in the disease. Muscle Nerve 30: 423–432, 2004
Developmental and tissue‐specific regulation of a novel dysferlin isoform
Authors: Salani Sabrina , Lucchiari Sabrina , Fortunato Francesco , Crimi Marco , Corti Stefania , Locatelli Federica , Bossolasco Patrizia , Bresolin Nereo , Comi Giacomo Pietro
Published: July 2004

Dysferlin plays an essential role in the muscle repair machinery, and its deficiency is associated with limb‐girdle muscular dystrophy type 2B and with two different distal myopathies (Miyoshi myopathy and distal anterior compartment myopathy). Our aims were to characterize the pattern of dysferlin expression during myogenic cell differentiation and to assess possible differentially spliced isoforms of the DYSF gene. Human primary myogenic cells express a splice variant of dysferlin mRNA lacking exon 17 (Δ17), together with full‐length dysferlin mRNA. Real‐time polymerase chain reaction analysis of human myoblasts, myotubes, and normal skeletal muscle showed that Δ17 expression inversely correlates with muscle differentiation. Indeed, Δ17 is progressively replaced by the wild type as myoblast fusion proceeds, and it disappears in adult skeletal muscle. Conversely, Δ17 is the predominant dysferlin variant in mature peripheral nerve. Our findings suggest that the two proteins play different roles in myogenic cell differentiation and that dysferlin function in peripheral nerve might be accomplished by this novel isoform. Muscle Nerve 30: 366–374, 2004
A coupled model for solid deformation and gas leak flow
Authors: Sun Peide , Wan Huagen
Published: July 2004

From the viewpoint of interaction mechanics of solid and gas, a coupled mathematical model is presented for solid coal/rock‐mass deformation and gas leak flow in parallel deformable coal seams. Numerical solutions using the strong implicit procedure (SIP) method to the coupled mathematical model for double parallel coal seams are also developed in detail. Numerical simulations for the prediction of safety range using protection layer mining are performed with experimental data from a mine with potential danger of coal/gas outbursts. Analyses show that the numerical simulation results are consistent with the measured data on the spot. The coupled model shows a positive future for applications in a wide range of gas‐leak‐flow‐related problems in mining engineering, gas drainage engineering and mining safety engineering. Copyright © 2004 John Wiley & Sons, Ltd.
Upscaling of elastic properties for large scale geomechanical simulations
Authors: Chalon F. , Mainguy M. , Longuemare P. , Lemonnier P.
Published: July 2004

Large scale geomechanical simulations are being increasingly used to model the compaction of stress dependent reservoirs, predict the long term integrity of under‐ground radioactive waste disposals, and analyse the viability of hot‐dry rock geothermal sites. These large scale simulations require the definition of homogenous mechanical properties for each geomechanical cell whereas the rock properties are expected to vary at a smaller scale. Therefore, this paper proposes a new methodology that makes possible to define the equivalent mechanical properties of the geomechanical cells using the fine scale information given in the geological model. This methodology is implemented on a synthetic reservoir case and two upscaling procedures providing the effective elastic properties of the Hooke's law are tested. The first upscaling procedure is an analytical method for perfectly stratified rock mass, whereas the second procedure computes lower and upper bounds of the equivalent properties with no assumption on the small scale heterogeneity distribution. Both procedures are applied to one geomechanical cell extracted from the reservoir structure. The results show that the analytical and numerical upscaling procedures provide accurate estimations of the effective parameters. Furthermore, a large scale simulation using the homogenized properties of each geomechanical cell calculated with the analytical method demonstrates that the overall behaviour of the reservoir structure is well reproduced for two different loading cases. Copyright © 2004 John Wiley & Sons, Ltd.
Semi‐analytical far field model for three‐dimensional finite‐element analysis
Authors: Doherty James P. , Deeks Andrew J.
Published: July 2004

A challenging computational problem arises when a discrete structure (e.g. foundation) interacts with an unbounded medium (e.g. deep soil deposit), particularly if general loading conditions and non‐linear material behaviour is assumed. In this paper, a novel method for dealing with such a problem is formulated by combining conventional three‐dimensional finite‐elements with the recently developed scaled boundary finite‐element method. The scaled boundary finite‐element method is a semi‐analytical technique based on finite‐elements that obtains a symmetric stiffness matrix with respect to degrees of freedom on a discretized boundary. The method is particularly well suited to modelling unbounded domains as analytical solutions are found in a radial co‐ordinate direction, but, unlike the boundary‐element method, no complex fundamental solution is required. A technique for coupling the stiffness matrix of bounded three‐dimensional finite‐element domain with the stiffness matrix of the unbounded scaled boundary finite‐element domain, which uses a Fourier series to model the variation of displacement in the circumferential direction of the cylindrical co‐ordinate system, is described. The accuracy and computational efficiency of the new formulation is demonstrated through the linear elastic analysis of rigid circular and square footings. Copyright © 2004 John Wiley & Sons, Ltd.
A new displacement back analysis to identify mechanical geo‐material parameters based on hybrid intelligent methodology
Authors: Feng Xia‐Ting , Zhao Hongbo , Li Shaojun
Published: July 2004

Displacement back analysis is a common method to identify mechanical geo‐material parameters using the monitored displacement. How to obtain a global optimum solution in large space search of highly non‐linear multimodal is a key point of optimum back analysis. The paper presents a new back analysis that is an integration of evolutionary support vector machines (SVMs), numerical analysis and genetic algorithm. The non‐linear relationship between the mechanical geo‐material parameters to be identified and the corresponding displacement values of key points is learned and represented by evolutionary SVMs in global optimum. Numerical analysis is used to create training and testing samples for recognition of SVMs. Then, performing a global optimum search on the obtained SVMs using genetic algorithm can identify the mechanical geo‐material parameters. The proposed algorithm is tested by back analysis of an elastic plate and an elastic–plastic plate and used to recognize mechanical parameters of subclay, strongly weathered tuff and weakly weathered tuff of Bachimen slope, Funing expressway, Fujian, China. The results indicate that applicability of the proposed algorithm with enough accuracy. Copyright © 2004 John Wiley & Sons, Ltd.
Agrin signaling in cortical neurons is mediated by a tyrosine kinase‐dependent increase in intracellular Ca2+ that engages both CaMKII and MAPK signal pathways
Authors: Hilgenberg Lutz G.W. , Smith Martin A.
Published: July 2004

Agrin has been implicated in multiple aspects of central nervous system (CNS) neuron differentiation and function including neurite formation, synaptogenesis, and synaptic transmission. However, little is known about the signaling mechanisms whereby agrin exerts its effects. We have recently identified a neuronal receptor for agrin, whose activation induces expression of c‐fos, and provided evidence that agrin binding to this receptor is associated with a rise in intracellular Ca2+, a ubiquitous second messenger capable of mediating a wide range of effects. To gain further insight into agrin's role in brain, we used Ca2+ imaging to explore agrin signal transduction in cultured cortical neurons. Bath application of either z+ or z‐agrin isoforms resulted in marked changes in intracellular Ca2+ concentration specifically in neurons. Propagation of the Ca2+ response was a two‐step process characterized by an initial increase in intracellular Ca2+ mediated by ryanodine receptor (RyR) release from intracellular stores, supplemented by influx through voltage‐gated calcium channels (VGCCs). Agrin‐induced increases in intracellular Ca2+ were blocked by genistein and herbimycin, suggesting that the agrin receptor is a tyrosine kinase. Ca2+ release from intracellular stores activates both calcium/calmodulin‐dependent kinase II (CaMKII) and mitogen activated protein kinase (MAPK). Activation of CaMKII is required for propagation of the Ca2+ wave itself, whereas both MAPK and CaMKII play a role in mediating long latency responses such as induction of c‐fos. These results suggest that an agrin‐dependent tyrosine kinase could play a critical role in modulating levels of intracellular Ca2+ and activity of MAPK and CaMKII in CNS neurons. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2004
Chemically controlled formation of a DNA/calcium phosphate coprecipitate: Application for transfection of mature hippocampal neurons
Authors: Goetze Bernhard , Grunewald Barbara , Baldassa Simona , Kiebler Michael
Published: July 2004

Numerous methods exist for transfecting postmitotic neurons, for example, DNA/calcium phosphate coprecipitation, cationic lipids, viruses, and physical methods such as microinjection, electroporation, and biolistics. Most methods, however, are either toxic to the cell, yield only poor transfection efficiencies, or cells have to be electroporated before plating. In this article, we present a standardized and fast transfection method using DNA/calcium phosphate coprecipitates that efficiently transfer DNA into mature, postmitotic hippocampal neurons. Shifting to CO2‐independent media with a well‐defined pH allows for the tight control of the coprecipitate formation and for adjusting the transfection parameters for the individual DNA plasmid used. The two critical parameters for reproducible and efficient transfections are: the precise pH during crystal formation, and the incubation time of the cells with the coprecipitate. This improved procedure now enables biochemical approaches. By transfecting a dominant‐positive Ras mutant, we activate the Erk/MAP kinase signal transduction pathway. Furthermore, using a siRNA plasmid directed against MAP2, the level of an endogenously expressed protein is down‐regulated upon transfection. These two approaches demonstrate that the presented transient transfection method can now be used to address questions on a biochemical level in hippocampal neurons. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 517–525, 2004
Mid‐chain grafting in PVB‐graft‐PVB
Authors: Striegel André M
Published: July 2004

The polymer commonly referred to as poly(vinyl butyral) is actually the statistical terpolymer poly(vinyl butyral‐co‐vinyl alcohol‐co‐vinyl acetate), the main component of the polymeric interlayer in automotive and architectural safety glass, amongst other uses. Here, the effects of ‘self‐grafting’ or ‘auto‐grafting’ in this polymer are examined using size‐exclusion chromatography (SEC) with triple detection. These and supporting experiments (eg, batch‐mode multi‐angle light scattering) allow study of the effects of induced branching in the resultant PVB‐graft‐PVB molecule, and comparison with the ungrafted (though not linear) base polymer. This was done by application and extension of the classic Zimm–Stockmayer long‐chain branching (LCB) theory, by determination of the fractal dimension (df) of the polymers and of the change in df as a function of molar mass, as well as by the multiplicity of size parameters that are measured in a multi‐detector SEC experiment. Copyright © 2004 Society of Chemical Industry
Flexibility improvement of epoxy resin by chemical modification
Authors: Ratna D , Samui AB , Chakraborty BC
Published: July 2004

Epoxy resin was chemically modified with carboxyl‐terminated poly(ethylene glycol) adipate (CTPEGA) and the modified epoxy networks were made by curing with an ambient‐temperature hardener. The modified epoxy networks containing various concentrations of CTPEGA were characterized for their tensile, flexural and impact properties. It was observed that the mechanical strength gradually decreases and the strain increases with increasing CTPEGA concentration. However, the toughness and impact strength gradually increase with increasing CTPEGA concentration, attain a maximum and then decrease. The optimum CTPEGA concentration was found to be 20 phr. Fracture surface analysis by scanning electron microscopy indicates massive plastic deformation in modified networks. Copyright © 2004 Society of Chemical Industry
Dark cure studies of cationic photopolymerizations of epoxides: Characterization of kinetic rate constants at high conversions
Authors: Sipani Vishal , Kirsch Ann , Scranton Alec B.
Published: July 2004

The effective propagation rate constant (kp; averaged over all the propagating active centers) was characterized for solvent‐free cationic photopolymerizations of phenyl glycidyl ether over the entire range of conversions, including the high conversion regime in which mass transfer limitations become important. The profile for the kp as a function of conversion was found to exhibit a constant plateau value at low to intermediate conversions, followed by a monotonic increase above a threshold value of conversion. To explain this trend, it is proposed that at high conversion the diffusional mobility of the photoinitiator counterion is reduced whereas the mobility of the cationic active center remains high because of reactive diffusion. Therefore, with increasing conversion, the average distance between the active centers and counterions may increase, resulting in an increase in the propagation rate constant. The profiles for the kp values were investigated as a function of the temperature, photoinitiator anion, and photoinitiator concentration. As the photoinitiator concentration was increased, the plateau value of the effective propagation rate constant decreased whereas the threshold conversion increased. All of the experimental trends are consistent with the proposed increase in ion separation at high conversions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4409–4416, 2004
Samarium enolate on crosslinked polystyrene beads. III. Anionic initiator for well‐defined synthesis of poly(hydroxyethyl methacrylate) on solid support
Authors: Tanaka Masayoshi , Sudo Atsushi , Endo Takeshi
Published: July 2004

A solid‐supported samarium enolate successfully initiated the polymerization of 2‐(trimethylsilyloxy)ethyl methacrylate (TMS‐HEMA) through the living anionic process. In addition, the silyl group was readily removed by treatment of the beads with a weak acid to afford the corresponding well‐defined poly(methacrylate) having a hydroxyethyl group in the side chain (PHEMA). The hydroxyl group of the immobilized PHEMA on the beads was successfully acetylated to give poly(2‐acetoxyethyl methacrylate), which could be quantitatively isolated from the beads by trifluoroacetic acid treatment. Moreover, the hydroxyl group of the immobilized PHEMA could be utilized as an initiator for acid promoted ring opening polymerization of lactone to yield the corresponding graft copolymer. In this method, the residual and excess reagents could be removed by filtration, which demonstrated the applicability of the present technique to a novel method for construction of functional polymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4417–4423, 2004
Synthesis and ring‐opening polymerization of new monoalkyl‐substituted lactides
Authors: Trimaille Thomas , Möller Michael , Gurny Robert
Published: July 2004

New monoalkyl‐substituted lactides were synthesized by reaction of α‐hydroxy acids with 2‐bromopropionyl bromide, and polymerized with various catalysts in the presence of benzyl alcohol by ring‐opening polymerization (ROP). The classic tin(II) 2‐ethylhexanoate (Sn(Oct)2) catalyst was leading to polymers with narrow distribution and predictable molecular weights, in polymerizations in bulk or toluene at 100 °C. The polymerization rate was corresponding to the steric hindrance of the alkyl substituents, such as butyl, hexyl, benzyl, isopropyl, and dimethyl groups. A yield of 83% was obtained with the hexyl‐substituted lactide after 1 h of polymerization. Excellent conversions (97%) could be achieved by using the alternative catalyst 4‐(dimethylamino)pyridine (DMAP). This latter organic catalyst was most efficient in polymerizing the more steric‐hindered lactides with good molecular weight and polydispersity control, in comparison to the tin(II) 2‐ethylhexanoate and tin(II) trifluoromethane sulfonate [Sn(OTf)2] catalysts. The efficiency of the DMAP catalyst and the variability of the monomer synthesis route for new alkyl‐substituted lactides allow to prepare and to envision a wide range of new functionalized polylactides for the elaboration of tailored materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4379–4391, 2004
Synthesis and characterization of polyurethane–urea nanoparticles containing methylenedi‐p‐phenyl diisocyanate and isophorone diisocyanate
Authors: Cheong In Woo , Kong Hyun Chul , An Jeong Ho , Kim Jung Hyun
Published: July 2004

Water‐based polyurethane–urea (WPUU) nanoparticles containing 4,4′‐methylenedi‐p‐phenyl diisocyanate (MDI) and isophorone diisocyanate (IPDI) were synthesized by a stepwise prepolymer mixing process, that is, the consecutive formation of hydroxyl‐terminated and isocyanate‐terminated polyurethane prepolymers. The reaction behavior, chemical structure, and consequent morphology of the polyurethane prepolymers and WPUU were investigated with Fourier transform infrared (FTIR), gel permeation chromatography, and NMR techniques with MDI concentrations ranging from 0 (pure IPDI) to 50% with respect to the total moles of isocyanate. Wide‐angle X‐ray diffraction and differential scanning calorimetry patterns showed that the crystallinity of WPUU, which mostly originated from crystallizable poly(tetramethylene adipate) polyol, was significantly affected by the MDI content. Both the crystallinity and melting temperature of WPUU decreased as the MDI content increased. Deconvoluted relative peak areas of the carbonyl region in the FTIR spectrum revealed that the effect of hydrogen bonding among the hard segments became favorable as the MDI content increased, whereas the hydrogen bonding of the soft segments significantly decreased. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4353–4369, 2004