bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine induces metalloproteinase and shedding of β‐1 integrin in microvessel endothelial cells
Authors: Shastry Suresh , Tyagi Suresh C.
Published: June 2004

Although studies have suggested microvessel endothelial cells (MVEC) activation and induction of matrix metalloproteinases (MMPs) by homocysteine (Hcy), the transduction mechanism leading to endothelial activation was unclear. We hypothesized that Hcy induced metalloproteinase and altered the levels of integrin in MVEC. MVEC from mouse brain were isolated and characterized by CD‐31 (PECAM‐1) FITC labeling. The MVEC were activated with different doses (6–40 μM) of Hcy. The cultured‐conditioned‐medium was analyzed for MMP activity by gelatin gel‐zymography. TIMP‐1, ‐4, β‐1 integrin, and a disintegrin and metalloproteinase‐12 (ADAM‐12) were quantified by Western blot analysis. We used MVEC in cell culture to study the effect of increasing concentrations of Hcy upon the secretion of various proteins into the culture medium. MMP‐9, β‐1 integrin, ADAM‐12, and TIMP‐1 were found in increased concentrations in the culture medium of Hcy‐treated cells whereas TIMP‐4 was decreased. We have shown that purified TIMP‐4 blocked the increase of β‐1 integrin shedding in Hcy‐treated cells. Interestingly, our results suggest that TIMP‐1 and TIMP‐4 function antagonistically in Hcy‐induced signaling pathways. © 2004 Wiley‐Liss, Inc.
Vitamin D3 modulated gene expression patterns in human primary normal and cancer prostate cells
Authors: Guzey Meral , Luo Jianhua , Getzenberg Robert H.
Published: June 2004

The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors and has potential tumor‐suppressive functions in prostate and other cancer types. Vitamin D3 (VD3) exerts its biological actions by binding within cells to VDR. The VDR then interacts with specific regions of the DNA in cells, and triggers changes in the activity of genes involved in cell division, cell survival, and cellular function. Using human primary cultures and the prostate cancer (PCa) cell line, ALVA‐31, we examined the effects of VD3 under different culture conditions. Complete G0/G1 arrest of ALVA‐31 cells and ∼50% inhibition of tumor stromal cell growth was observed. To determine changes in gene expression patterns related to VD3 activity, microarray analysis was performed. More than ∼20,000 genes were evaluated for twofold relative increases and decreases in expression levels. A number of the gene targets that were up‐ and down‐regulated are related to potential mechanisms of prostatic growth regulation. These include estrogen receptor (ER), heat shock proteins: 70 and 90, Apaf1, Her‐2/neu, and paxillin. Utilizing antibodies generated against these targets, we were able to confirm the changes at the protein level. These newly reported gene expression patterns provide novel information not only potential markers, but also on the genes involved in VD3 induced apoptosis in PCa. © 2004 Wiley‐Liss, Inc.
Analysis of discontinuities in rectangular ducts and higher order mode excitations using TLM and FEM methods
Authors: El‐Masri Samir
Published: June 2004

In acoustic waveguide, it is believed that higher order modes have a dramatic effect on the behaviour of the global acoustic waves when the frequency of the source is above the cut‐off frequency of the duct. In this paper, we are going to study the influence of the discontinuities on the excitation and the propagation of higher order modes in symmetrical and non‐symmetrical ducts using theoretical analysis and numerical simulations. As for numerical simulations, transmission line matrix (TLM) method and finite element method (FEM) will be used. Moreover, we will try here to compare the two numerical methods, showing their advantages and disadvantages. The transfer functions of symmetrical and non‐symmetrical ducts will also be shown and discussed as well as numerical simulations of the acoustic pressure into the duct in three‐dimensional (3‐D) system. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluation of the optimum tilt of a PV array using maximum global insolation technique
Authors: Nafeh Abd El‐Shafy A.
Published: June 2004

The photovoltaic (PV) is considered to be the most promising energy source in many applications, due to its safety and high reliability. But the initial high cost of the PV arrays and the large areas necessitate their optimum use. One of the solutions that optimizes the array performance is to what extent the array tilt should be adjusted such that the incident insolation on the array becomes as large as possible. In this paper, a new technique, which maximizes the incident solar insolation at solar noon on the tilted PV array, is proposed and developed. The monthly mean values of the solar insolation incident on a horizontal surface is calculated using a statistical methods. Also, a comparison between the proposed technique and the most common one is studied. The results indicate the superiority of the proposed technique. Copyright © 2004 John Wiley & Sons, Ltd.
Physically based 2D compact model for power bipolar devices
Authors: Igic P. M. , Towers M. S. , Mawby P. A.
Published: June 2004

The two‐dimensional (2D) physical compact model for advanced power bipolar devices such as injection enhanced gate transistor (IEGT) or Trench IGBT is presented in this paper. In order to model the complex 2D nature of these devices the ambipolar diffusion equation has been solved simultaneously for different boundary conditions associated with different areas of the device. The IEGT compact model has been incorporated into the SABER simulator and tested in standard double‐pulse switching test circuit. The compact model has been established to model a 4500V‐1500A flat pack TOSHIBA IEGT. Copyright © 2004 John Wiley & Sons, Ltd.
Atmospheric transmissivity: distribution and empirical estimation around the central Andes
Authors: Baigorria Guillermo A. , Villegas Esequiel B. , Trebejo Irene , Carlos Jose F. , Quiroz Roberto
Published: June 2004

This study of the distribution in space and time of atmospheric transmissivity τ takes into account the fact that, in complex terrain, many factors affect this variable; thus, it is not possible to use the generalizations that can be applied under more homogeneous conditions. Climatic controls, topography and even sea currents have important effects on clouds and aerosols affecting τ, simultaneously leading to differences in the distribution of incident solar radiation. Different models exist to estimate incoming solar radiation as a function of relative sunshine hours (observed sunshine hours/theoretical sunshine hours, n/N) or differences between maximum and minimum temperatures Δ T. We calibrated, validated and evaluated four of these empirical relations based on data from 15 weather stations in Peru. Models were calibrated using 66% of the daily historical record available for each weather station; the rest of the information was used for validation and comparison. The Ångström–Prescott model was used to estimate incoming solar radiation based on n/N, and gave the best performance of all the models tested. The other models (Bristow–Campbell, Hargreaves, and Garcia) estimated incoming solar radiation based on Δ T. Of all the models in this group, the Bristow–Campbell model performed best; it is also valuable because of the physical explanation involved. The empirical coefficients of all the models evaluated are presented here. Two empirical equations are proposed with which to estimate values of the coefficients bB and cB in the Bristow–Campbell model, as a function of Δ T and latitude, allowing the model to be applied to other study areas. Copyright © 2004 Royal Meteorological Society
Changes in Australian pan evaporation from 1970 to 2002
Authors: Roderick Michael L. , Farquhar Graham D.
Published: June 2004

Contrary to expectations, measurements of pan evaporation show decreases in many parts of the Northern Hemisphere over the last 50 years. When combined with rainfall measurements, these data show that much of the Northern Hemisphere's terrestrial surface has become less arid over the last 50 years. However, whether the decrease in pan evaporation is a phenomenon limited to the Northern Hemisphere has until now been unknown because there have been no reports from the Southern Hemisphere. Here, we report a decrease in pan evaporation rate over the last 30 years across Australia of the same magnitude as the Northern Hemisphere trends (approximately −4 mm a−2). The results show that the terrestrial surface in Australia has, on average, become less arid over the recent past, just like much of the Northern Hemisphere. Copyright © 2004 Royal Meteorological Society.
Optimization of micellar liquid chromatographic separation of polycyclic aromatic hydrocarbons with the addition of second organic additive
Authors: Mao Chunfeng , McGill Kelly E. , Tucker Sheryl A.
Published: June 2004

The micellar liquid chromatographic (MLC) separations of polycyclic aromatic hydrocarbons (PAHs) were optimized for three micellar systems, cetyltrimethylammonium chloride (CTAC), dodecyltrimethylammonium chloride (DTAC), and sodium dodecylsulfate (SDS), with 1‐pentanol as the only organic additive. A difference in the separation was observed between CTAC and SDS/DTAC. Under each optimized separation conditions, CTAC‐modified mobile phase provides the least desirable separation, which is attributed to its longer carbon tail (C16 vs. C12). In addition to 1‐pentanol, the main organic additive, a second organic additive (3% 1‐propanol) in the micelle‐modified mobile phase was found to enhance the resolution of PAH chromatographic peaks. However, the extent of the enhancement varies for the different micellar systems, with the greatest resolution improvement seen for CTAC, and little effect for shorter‐tail SDS and DTAC. This study shows the potential use of second organic additive (1‐propanol), to the main nonpolar additive (1‐pentanol), in facilitating the MLC separation of larger nonpolar compounds.
The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: A systematic review and meta-analysis†
Authors: Safdar Nasia , Said Adnan , Lucey Michael R.
Published: June 2004

Selective digestive decontamination (SDD) refers to the use of antimicrobials to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract to prevent infections caused by these organisms. Liver transplant patients are highly vulnerable to bacterial infection particularly with gram-negative organisms within the first month after transplantation, and SDD has been proposed as a potential measure to prevent these infections. However, the benefit of this procedure remains controversial. We undertook a systematic review and meta-analysis to determine whether SDD is beneficial in reducing infections overall and those caused by gram-negative bacteria in patients following liver transplantation. All studies that evaluated the efficacy of SDD in liver transplant patients were included. Randomized trials that included liver transplant patients given SDD versus either placebo or no treatment or minimal treatment (e.g., oral nystatin alone), and that provided adequate data to calculate a relative risk ratio, were included in the meta-analysis. Our review shows that most studies found SDD to be effective in reducing gram-negative infection. The nonrandomized and uncontrolled trials also showed benefit with SDD in reducing overall infection; however, the effect on overall infection was limited in the 4 randomized trials, in which the pooled relative risk was 0.88 (95% CI, 0.7-1.1), indicating no statistically significant reduction in infection with the use of SDD. The summary risk ratio for the association between SDD and gram-negative infection was 0.16 (95% CI, 0.07-0.37), indicating an 84% relative risk reduction in the incidence of infection caused by gram-negative bacteria in patients receiving SDD in randomized trials. In conclusion, the available literature supports a beneficial effect of SDD on gram-negative infection following liver transplantation; however, the risk of antimicrobial resistance must be considered. Larger multicenter randomized trials in this patient population to assess the effect of SDD in reducing infection and mortality, while assessing the risk of antimicrobial resistance, are needed. (Liver Transpl 2004;10:817-827.)
Recovery from a variegate porphyria by a liver transplantation
Authors: Stojeba Nathalie , Meyer Carole , Jeanpierre Catherine , Perrot Frédéric , Hirth Christine , Pottecher Thierry , Deybach Jean-Charles
Published: June 2004

The porphyrias are a group of inherited or acquired enzymatic defects of heme biosynthesis. Each type of porphyria has a characteristic pattern of overproduction and accumulation of heme precursors based on the location of dysfunctional enzyme in the heme synthetic pathway. Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. A case of liver transplantation is described with a recovery from a variegate porphyria. Acute porphyria is commonly worsened by a wide variety of medications. We describe a step-by-step perioperative management protocol. (Liver Transpl 2004;10:935-938.)
Survival after liver transplantation in the United States: A disease-specific analysis of the UNOS database
Authors: Roberts Mark S. , Angus Derek C. , Bryce Cindy L. , Valenta Zdenek , Weissfeld Lisa
Published: June 2004

Our goal was to describe disease-specific survival and the clinical variables that predict survival in a large national cohort of adult liver transplant recipients. Data on 17,044 adult patients who received an initial orthotopic liver transplant between 1990 and 1996 with follow-up through 1999 was obtained from the United Network for Organ Sharing (UNOS). Disease-specific Kaplan-Meier survival plots and Cox Proportional Hazards models were estimated, and differences in the clinical characteristics of patients at the time of transplantation by disease were examined. Overall posttransplant survival currently exceeds 85% in the first year and is approaching 75% at 5 years. Unadjusted Kaplan-Meier survival is improved for recipients who are younger, female, and in better clinical condition. Survival is a function of disease and level of illness: cancer, fulminant liver failure, alcoholic liver disease, and the hepatitidies have the poorest prognosis, while primary billiary cirrohsis and sclerosing cholangitis have the best. Recipients who were outpatients before transplantation have longer survival than those transplanted from the hospital or intensive care unit. Although the model for end-stage liver disease (MELD) score was designed to predict pretransplant survival, patients with higher MELD scores have poorer posttransplant survival, but the MELD score is less predictive than the specific disease. Differences in disease-specific survival are partially explained by differences in disease severity at the time of transplantation. In conclusion, Disease-specific survival models indicate that there remains tremendous variability in survival as a function of underlying liver disease. However, a significant portion of the difference in survival between diseases arises from differences in clinical characteristics at the time of transplantation. (Liver Transpl 2004;10:886-897.)
A comparison of disease severity and survival rates after liver transplantation in the United Kingdom, Canada, and the United States
Authors: Stell David A. , McAlister Vivian C. , Thorburn Douglas
Published: June 2004

The severity of preoperative liver disease influences the outcome of liver transplantation, is commonly used to determine priority on liver transplant waiting lists, and may differ between countries with different rates of liver disease and organ allocation systems. We compared the relative severity of liver disease in transplant recipients with chronic liver disease in the United States, Canada, and the United Kingdom and its relation to outcome. Data were obtained from national databases on patients who received transplants in the year 2000. The data included age, gender, diagnosis, the status at the time of transplantation, and indices of chronic liver disease [serum bilirubin and international normalized ratio (INR), and serum creatinine] from which a comparative score [model for end-stage liver disease (MELD) score] was calculated. The data revealed marked differences between the three countries. No patient in the United Kingdom was in intensive care before transplantation compared with 19.3% of recipients in the United States and 7.5% in Canada. The median model MELD score of recipients in the United Kingdom was 10.9 compared with 16.1 in the United States and 17 in Canada. The median MELD score of transplant recipients in North America did not vary according to diagnosis, whereas in the United Kingdom, patients with cholestatic liver disease had a lower median MELD score (8.5) than those with alcoholic liver disease (15.7) at the time of transplantation. In conclusion, the disease severity of UK liver transplant recipients varied by diagnosis and was lower than recipients in North America; the 1-year survival rate was, however, similar between the countries. (Liver Transpl 2004;10:898-902.)
Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome
Authors: Shetty Kirti , Timmins Kate , Brensinger Colleen , Furth Emma E. , Rattan Sushil , Sun Weijing , Rosen Mark , Soulen Michael , Shaked Abraham , Reddy Rajender K. , Olthoff Kim M.
Published: June 2004

Appropriate patient selection is crucial in ensuring acceptable outcomes from orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The United Network for Organ Sharing (UNOS) has elected to prioritize HCC patients for OLT based on criteria of tumor burden. However, it is unclear whether these criteria correlate with outcome, or with the pathobiological features associated with tumor recurrence. Therefore, we analyzed 109 consecutive patients undergoing OLT for HCC at our center, to determine the utility of present selection criteria in predicting outcome. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified tumor node metastases (pTNM) classification system. Multifocality was defined as >4 tumor nodules on explant. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. At a median follow-up of 18.9 months, the overall mortality was 19% with 15 patients (14%) dying of recurrent HCC. Kaplan-Meier 1, 3 and 5-year survival rates were 89.5%, 68%, and 65%, respectively. Recurrence-free rates of 1, 3, and 5 years were 89%, 75%, and 65%, respectively. On univariate analysis, the factors found to be significantly associated with recurrence of HCC were explant features of macrovascular invasion, tumor size (per centimeter increase), pTNM stage (per 1-stage increase), and pre-transplant serum alphafetoprotein (AFP) >300 ng/mL. In defining a threshold level, we found that explant tumor diameter ≥3 cm, and those tumors classified as at least pT3 on pathological examination, were significantly associated with recurrence (P = .01 and .03, respectively). Tumor size on explant was found to be strongly correlated with multifocality (P = .017) and vascular invasion (P = .02). Patients exceeding pathological UNOS criteria were 3.1 times more likely to have recurrence of HCC (P = .03). In conclusion, we found that tumor size appears to be a surrogate marker for negative pathobiological predictors of outcome, i.e., vascular invasion and multifocality. Present UNOS selection criteria for HCC based on tumor burden appear to provide adequate discriminatory power in predicting outcome of OLT. (Liver Transpl 2004;10:911-918.)
Tacrolimus ameliorates cerebral vasodilatation and intracranial hypertension in the rat with portacaval anastomosis and hyperammonemia
Authors: Dethloff Thomas , Hansen Bent Adel , Larsen Fin Stolze
Published: June 2004

Arterial hyperammonemia and cerebral vasodilatation correlate with cerebral herniation in patients with fulminant hepatic failure (FHF). Tacrolimus is a calcineurin inhibitor that passes the blood-brain barrier and may increase cerebrovascular tone and restrict cerebral ammonia influx. In this study, we determined if tacrolimus prevents cerebral vasodilatation and high intracranial pressure (ICP) in the rat with portacaval anastomosis (PCA) challenged to high arterial ammonia (NH4+) concentration. Seven groups of mechanically ventilated rats, with 6-9 rats in each group, were investigated within 48 hours after construction of a PCA (4 groups) or after sham operation (3 groups). Three groups of the rats received infusion of NH4+ and 4 groups received saline for approximately 180 minutes. Two groups of the PCA rats receiving either NH4+ or saline had an i.v. injection of tacrolimus (0.4 mg/kg) or vehicle before start of NH4+ or saline infusion. Cerebral blood flow (CBF) was monitored by a laser Doppler probe in brain cortex. ICP was monitored by placement of a catheter in the cerebrospinal fluid. CBF and ICP increased in PCA rats receiving NH4+ infusion compared to PCA controls and to all groups of sham-operated animals (P < .05). In the group of PCA rats pre-treated with tacrolimus before receiving ammonia infusion, the increase in ICP was ameliorated compared to the ammonia infused group receiving vehicle (P < .03). Tacrolimus also prevented an increase in CBF in the PCA group receiving NH4+ (P < .05) compared to the control groups. In conclusion, Tacrolimus prevents cerebral vasodilatation and ameliorates intracranial hypertension in PCA rats receiving NH4+ infusion. These findings indicate that tacrolimus could be of clinical value in the prevention of cerebral hyperemia, high ICP, and serious brain damage in patients with FHF. (Liver Transpl 2004;10:922-927.)
Bile duct strictures after adult liver transplantation: A role for biliary reconstructive surgery?
Authors: Sutcliffe Robert , Maguire Donal , Mróz Andrej , Portmann Bernard , O’Grady John , Bowles Matthew , Muiesan Paolo , Rela Mohamed , Heaton Nigel
Published: June 2004

There is no accurate method to determine the functional significance of bile duct strictures after liver transplantation, and although biliary reconstructive surgery (Roux-en-Y hepaticojejunostomy, HJ) is the second-line treatment in patients with persistent allograft dysfunction following failed endoscopic therapy, there is no evidence to support this approach. Liver transplant recipients with allograft dysfunction and demonstrable bile duct strictures who had undergone hepaticojejunostomy were identified from a prospective database. Preoperative and follow-up clinical, biochemical, and radiological data were collected. Perioperative liver biopsies were evaluated prospectively by two histopathologists blinded to clinical information. The biopsies were scored according to presence and severity of biliary features, fibrosis, and coexisting diseases. The effects of preoperative factors on postoperative allograft function were analyzed using SPSS statistical software. After hepatico-jejunostomy, graft function returned to normal in 8/44 patients (18%), improved in 16/44 (36%), but remained abnormal in 20/44 (45%), including 4 patients who subsequently underwent retransplantation. Hepaticojejunostomy was more likely to yield a favorable outcome (improved or normal graft function) when performed within 2 years of transplantation. Prolonged duration of biliary obstruction was associated with development of advanced graft fibrosis at the time of surgery, but neither factor significantly influenced postoperative graft function. In conclusion, biliary reconstruction successfully restores graft function in the majority of patients who present with anastomotic strictures within the first 2 years after liver transplantation. In patients presenting with bile duct strictures late after transplantation, surgery should be reserved for selected patients without histological evidence of graft fibrosis (moderate-severe) or significant nonbiliary pathology. (Liver Transpl 2004;10:928-.934)
Analyzing liver transplantation for fulminant hepatic failure at UCLA: A retrospective look at 18 years’ experience
Authors: Lee William M. , Polson Julie
Published: June 2004

Objective

To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome.

Summary background data

FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT.

Methods

A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival.

Results

Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and bound for intensive care. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival.

Conclusions

This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome. (Ann Surg 2003;237:666-676.)
Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation
Authors: Makisalo Heikki , Koivusalo Anu , Vakkuri Anne , Hockerstedt Krister
Published: June 2004

Liver transplantation (LT) may be indicated in cirrhotic patients with underlying pulmonary artery hypertension. However, severe pulmonary artery hypertension with mean pulmonary artery pressure (mPAP) above 50 mmHg has even been considered a contraindication to LT. We present a cirrhotic patient with an mPAP of 56 mmHg measured using right heart catheterization (RHC) and with severely compromised physical capacity. She was first treated with sildenafil (Viagra®), a potent novel vasodilator, and successfully transplanted later. The mPAP decreased with sildenafil to the level of 28-31 mmHg and her general condition improved markedly. An LT using piggyback technique was performed 16 weeks later. Despite 2 reoperations for bleeding, the outcome has been excellent. In conclusion, treatment of severe portopulmonary hypertension (PHT) with sildenafil is effective. If a decrease in mPAP is achieved with sildenafil, it may improve the result of LT, even though no evidence of reversibility of PPHTN exists. (Liver Transpl 2004;10:945-950.)
Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients
Authors: Vogel Martin , Voigt Esther , Michaelis Hans-Christoph , Sudhop Thomas , Wolff Martin , Türler Andreas , Sauerbruch Tilman , Rockstroh Jürgen Kurt , Spengler Ulrich
Published: June 2004

Highly active antiretroviral therapy (HAART) has improved the life expectancy of HIV-infected patients, allowing orthotopic liver transplantation as a reasonable treatment option for selected patients with terminal liver disease. Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements of HAART, give rise to substantial drug-to-drug interactions with immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given. To avoid toxic drug levels, we used an orally available cyclosporine A formulation prepared from the commercial available intravenous solution, which enabled dose adjustments in 1-mg increments. Under ritonavir-boosted HAART, cyclosporine A levels showed markedly altered absorption/elimination characteristics with more or less constant blood-levels throughout the dosing interval and prolonged elimination half-lives up to 38 hours. To obtain equivalent areas under the curve of cyclosporine A, daily doses were reduced to 5-20% of the individual standard doses given before initiation of ritonavir-boosted HAART. Because of the flat absorption/elimination profiles under ritonavir-boosted HAART cyclosporine A, dosing could be reliably monitored long term by measuring cyclosporine A trough-levels. (Liver Transpl 2004;10:939-944.)
Cyclosporine A-Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation
Authors: Hulzebos Christian V. , Bijleveld Charles M.A. , Stellaard Frans , Kuipers Folkert , Fidler Vaclav , Slooff Maarten J.H. , Peeters Paul M.J.G. , Sauer Pieter J.J. , Verkade Henkjan J.
Published: June 2004

Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3-16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (+38%, P < .001) and cholate (+21%, P < .05) and the pool size of chenodeoxycholate (+54%, P < .001). Discontinuation of CsA decreased plasma levels of cholesterol (-18%, P < .05) and triglycerides (-23%, P < .05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [rs] = −0.82, P < .01) and plasma triglyceride levels (rs = −0.62, P < .05). In conclusion, CsA inhibits bile salt synthesis and increases plasma concentration of cholesterol and triglycerides in pediatric liver transplant patients. Suppression of bile salt synthesis by long-term CsA treatment may contribute to hyperlipidemia and thus to increased risk for cardiovascular disease. (Liver Transpl 2004;10:872-880.)
Pretransplant MELD score and post liver transplantation survival in the UK and Ireland
Authors: Jacob Mathew , Copley Lynn P. , Lewsey James D. , Gimson Alex , Toogood Giles J. , Rela Mohamed , van der Meulen Jan H. P.
Published: June 2004

It has been shown that the model for end-stage liver disease (MELD) score is an accurate predictor of survival in patients with liver disease without transplantation. Four recent studies carried out in the United States have demonstrated that the MELD score obtained immediately prior to transplantation is also associated with post-transplant patient survival. Our aim was to evaluate how accurately the MELD score predicts 90-day post-transplant survival in adult patients with chronic liver disease in the UK and Ireland. The UK and Ireland Liver Transplant Audit has data on all liver transplants since 1994. We studied survival of 3838 adult patients after first elective liver transplantation according to United Network for Organ Sharing categories of their MELD scores (≤ 10, 11-18, 19-24, 25-35, ≥36). The overall survival at 90-days was 90.2%. The 90-day survival varied according to the United Network for Organ Sharing MELD categories (92.6%, 91.9%, 89.7%, 89.7%, and 70.8%, respectively; P < 0.01). Therefore, only those patients with a MELD score of 36 or higher (3% of the patients) had a survival that was markedly lower than the rest. As a consequence, the ability of the MELD score to discriminate between patients who were dead or alive was poor (c-statistic 0.58). Re-estimating the coefficients in the MELD regression model, even allowing for nonlinear relationships, did not improve its discriminatory ability. In conclusion, in the UK and Ireland the MELD score is significantly associated with post-transplant survival, but its predictive ability is poor. These results are in agreement with results found in the United States. Therefore, the most appropriate system to support patient selection for transplantation will be one that combines a pretransplant survival model (e.g., MELD score) with a properly developed post-transplant survival model. (Liver Transpl 2004;10:903-907.)
Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation
Authors: Stravitz Todd R. , Shiffman Mitchell L. , Sanyal Arun J. , Luketic Velimir A. , Sterling Richard K. , Heuman Douglas M. , Ashworth April , Mills Scott A. , Contos Melissa , Cotterell Adrian H. , Maluf Daniel , Posner Marc P. , Fisher Robert A.
Published: June 2004

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon α-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 ± 2.37 vs. 5.64 ± 2.94 units before and after treatment, respectively; P = .016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P < .01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection. (Liver Transpl 2004;10:850-858.)
Porous Superabsorbent Hydrogel Composites: Synthesis, Morphology and Swelling Rate
Authors: Kabiri Kourosh , Zohuriaan‐Mehr Mahammad J.
Published: June 2004

Summary: Novel porous hydrogel composites with very high swelling capacity and enhanced rate of water absorption were synthesized in aqueous media at room temperature under normal atmospheric conditions. The porosity was induced through either foaming conducted in the course of polymerization or non‐solvent dewatering of the as‐synthesized gels. Kaolin was incorporated as an inorganic component in the polymerization process. The foaming technique was used to form porosity using three systems of different porogens (porosity generators), i.e. sodium bicarbonate, acetone and their combination. The as‐synthesized gels were dried through oven drying and non‐solvent dewatering. Morphology and swelling rate of the superabsorbent hydrogel composites (SHCs) were studied versus either the porogen system or the drying method. It was found that the simultaneous polymerization‐foaming technique had great influence on the improvement of porosity, morphology of the porous structure and the rate of water absorption. It was also shown that the drying procedure had remarkable influence on preserving the preformed porosity. Methanol as a dewatering solvent produced SHCs with higher porosity and swelling rate in comparison with the porosity of the hydrogels dewatered in acetone. Our invented methodology including simultaneous polymerization and foam formation using dual‐porogen system and the subsequent methanol‐dewatering approach was found to be the most efficient, highly practical, and cost‐effective route for preparing improved superabsorbing hydrogel materials.

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Ternary Blends to Improve Heat Distortion Temperature and Rheological Properties of PVC
Authors: de Zarraga Arantxa , Villanueva Sara , Muñoz Maria Eugenia , Obeso Rafael , Peña Juan José , Pascual Belén , Santamaría Anton
Published: June 2004

Summary: Binary and ternary blends of PVC mixed with α‐methylstyrene/acrylonitrile‐butadiene‐styrene copolymer (AMS‐ABS) and ethylene/vinyl acetate/carbon monoxide terpolymer (EVA‐CO) are investigated, with the aim to obtain a new PVC based material with an improved heat distortion temperature and good processability. Dynamic Mechanical Thermal Analysis (DMTA) reveals that ternary PVC/AMS‐ABS/EVA‐CO blends exhibit two glass transition temperatures: the lower Tg corresponds to a PVC/EVA‐CO phase and the higher one to a PVC/AMS‐ABS phase. An analysis of PVC respective interactions with AMS‐ABS and EVA‐CO leads to assert that the distribution of PVC in the ternary PVC/AMS‐ABS/EVA‐CO system is basically controlled by the binary immiscible blend composition, taken as Φ AMS‐ABS/Φ EVA‐CO ratio. The inclusion of AMS‐ABS and EVA‐CO to form ternary blends based on PVC, allows to improve heat distortion temperature (owed to the presence of AMS‐ABS), maintaining a low viscosity in the molten state, due to the plasticizing effect of EVA‐CO.

Viscosity function obtained at T = 170 °C from extrusion capillary measurements.

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Viscosity function obtained at T = 170 °C from extrusion capillary measurements.
Isobornyl Methacrylate as a Reactive Solvent of Polyethylene
Authors: Schnell Matthias , Borrajo Julio , Williams Roberto J. J. , Wolf Bernhard A.
Published: June 2004

Summary: Solutions containing 15 wt.‐% of a low‐molar‐mass polyethylene (PE) in isobornyl methacrylate (IBoMA), containing 0, 5 or 10 wt.‐% of 1,4 butanediol dimethacrylate (BDDMA) as crosslinker, were polymerized using either benzoyl peroxide (BPO), at 80 °C, or dicumyl peroxide (DCPO), with a thermal cycle attaining 150 °C, as initiators. Phase separation of an amorphous PE‐rich phase took place when carrying out the reaction at temperatures higher than the PE melting temperature. Partial crystallization of PE was observed when cooling to room temperature. Depending on the initial amount of BDDMA, the fraction of PE that was phase separated varied between 57 and 66% of the initial amount, with crystalline fractions in the range of 15 to 42%. The use of IBoMA as a reactive solvent of PE has two main advantages over other reactive solvents reported in the literature: a) it has a very low vapor pressure, and b) its free‐radical polymerization gives a polymer with a relatively high glass transition temperature.

Part of the cloud‐point curve for IBoMa, PIBoMA and PE solutions at 80 °C.

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Part of the cloud‐point curve for IBoMa, PIBoMA and PE solutions at 80 °C.
Recent data on the number of active centers and propagation rate constants in olefin polymerization with supported ZN catalysts
Authors: Zakharov V.A. , Bukatov G.D. , Barabanov A.A.
Published: June 2004

Data on the number of active centers (Cp) and propagation rate constants (Kp) have been obtained by means of polymerization quenching with 14CO of propylene and ethylene polymerization with supported titanium‐magnesium catalysts (TMC) with different composition. In the case of propylene polymerization the Cp and Kp values have been measured separately for isospecific, aspecific and low stereospecific centers. Effects of MgCl2 support, internal and external donors are discussed on the basis of data obtained.

Data on the strong effect of diffusion limitation at ethylene polymerization with number of TMC have been obtained and a set of methods have been used to exclude this effect. Data on Cp and Kp values at ethylene polymerization with low stereospecific and highly stereospecific catalysts are presented.
Comparison of silyl chromate and chromium oxide based olefin polymerization catalysts
Authors: Cann Kevin , Apecetche Maria , Zhang Minghui
Published: June 2004

A comparison of the ethylene polymerization performance conducted with an oxo and a triphenylsilyl chromate catalyst on silica was performed. The oxo catalyst has higher activity and better comonomer response. The silylchromate catalyst has a much longer induction time and made a much broader molecular weight distribution polymer compared to the oxo analogue. Performance similar to silylchromate on silica was observed when triphenylsilanol (TPS) was added to the oxo chromium catalyst. The oxo catalyst was converted to the silyl chromate catalyst by ligand substitution. Analysis of the catalyst components when TPS was added to the oxo chrome analogue showed that bis triphenylsilyl chromate can form and be removed from the support.
D/A‐metallocenes: the new dimension in catalyst design
Authors: Starzewski Aleksander Ostoja
Published: June 2004

D/A metallocenes constitute a novel unique class of catalysts, in that they are able to express structural information within the elementary steps of the catalytic cycle out of bridged as well as out of unbridged states due to the coexistence of donor (D) and acceptor (A) atoms in complex sandwich structures. Highly polarized transannular bridging interactions as well as Lewis basic and Lewis acidic functionalities in unbridged states are the prerequisites which define a modular highly flexible catalyst system with outstanding options to tailor materials and processes.
Microstructural characteristics and thermal properties of ansa‐zirconocene catalyzed copolymers of propene with higher α‐olefins
Authors: Sacchi Maria Carmela , Fortini Fabrizio , Losio Simona , Tritto Incoronata , Costa Giovanna , Stagnaro Paola , Tincul Ioan , Wahner Udo M.
Published: June 2004

Copolymers of propene and several higher α‐olefins, 1‐butene, 1‐pentene, 1‐hexene, 1‐heptene, 1‐octene, and 4‐methyl‐1‐pentene (4M1P), have been prepared with two different metallocene catalysts, rac‐Et(Ind)2ZrCl2 (EI) and rac‐Me2Si(2‐MeBenz‐[e]Ind)2ZrCl2 (MBI), and comprehensively characterized by 13C NMR spectroscopy. All copolymers produced with EI have comparable isotacticities as well as similar stereosequences. The copolymers produced with MBI significantly differ both from the reference propene homopolymer and among themselves: in fact, they are characterized by rather low isotacticities and the degree of tacticity is strongly influenced by comonomer type and concentration. A detailed 13C NMR analysis revealed that these copolymers are constituted by highly isotactic and atactic sequences of various lengths. The similar thermal behavior, in terms of transition temperatures, for the homologues of the series obtained with the two different catalysts show that the capability of crystallization of these systems is not directly connected to the overall microstructural properties (e.g. the isotacticity index) but can be accounted for by the details of the microstructure.
Relative reactivity enhancement of (Me5Cp)2ZrCl2 in mixture with (1,2,4‐Me3Cp)2ZrCl2 during ethene/1‐hexene copolymerization
Authors: Bruaseth Ingvild , Rytter Erling
Published: June 2004

Dual‐site ethene/1‐hexene copolymerizations with MAO‐activated (1,2,4‐Me3Cp)2ZrCl2 and (Me5Cp)2ZrCl2 catalysts were performed. Copolymers with narrow molecular weight distributions and bimodal short chain branching distributions could be produced. The combined catalyst system demonstrates a number of discrepancies from an expected average behavior of the individual sites. Dual‐site (1,2,4‐Me3Cp)2ZrCl2/(Me5Cp)2ZrCl2 systems produce copolymers with lower incorporation than expected. Clear evidences for relative activity enhancement of the (Me5Cp)2ZrCl2 catalyst in the mixture were observed in melting endotherms and Crystaf profiles. Molecular weights obtained by the mixture were higher than for any of the individual catalysts. A similar effect is observed for a dual‐site system of the (1,2,4‐Me3Cp)2ZrCl2 catalyst together with the Me4Si2(Me4Cp)2ZrCl2 catalyst as an alternative to (Me5Cp)2ZrCl2.
Sterically demanding bis(2‐silylindenyl)zirconium(IV) dichlorides as polymerisation catalyst precursors
Authors: Hannisdal Andreas , Möller Andreas C. , Rytter Erling , Blom Richard
Published: June 2004

A set of different 1‐ and 2‐silyl‐substituted zirconocene dichloride/MAO catalyst systems was investigated with respect to their performance in ethene/1‐hexene copolymerisations. In‐depth studies of bis(2‐dimethylsilylindenyl) zirconium(IV) dichloride (1) revealed a multi‐site behaviour, illustrating sensitivity to the reaction temperature and the comonomer mole fraction. Surprisingly, an upper limit is observed for the latter, leading to complete catalyst inhibition. Analysis of the chain termination processes implies the possibility of a predominant, although in general less favourable, β‐hydride elimination route under certain polymerisation conditions.
From zirconium to titanium: the effect of the metal in propylene polymerisation using fluxional unbridged bicyclic catalysts
Authors: Polo Eleonora , Losio Simona , Fortini Fabrizio , Locatelli Paolo , Sacchi Maria Carmela
Published: June 2004

Catalytic systems based on unbridged substituted indenyl systems are becoming of interest in the production of elastomeric polypropylene. A full understanding of the structural features necessary to control this kind of behaviour has not yet been achieved, since relatively slight changes in the molecular architecture can lead to polymers with remarkably different properties.

We report here our recent findings regarding the study of bicyclic zirconium and titanium complexes as fluxional catalysts in propylene polymerisation. Most of them have been synthesised according to a synthetic procedure that allowed us to prepare a series of complexes in which the ring fused to the cyclopentadienyl moiety is saturated and of different sizes, thus introducing a flexibility parameter that can be finely tuned.

The results obtained show that the stereoselectivity induced by this class of catalysts strongly depends both on the structure of the ligand and on the nature of metal atom (Zr vs. Ti). The titanium‐based catalysts yield polypropylenes with new and interesting microstructures, in particular when an higher stability is achieved through a careful choice of the substitution pattern of the ligands.