bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface modification of polyimide film by ion implantation
Authors: Kim Jong‐Taek , Park Jong‐Kwan , Lee Duck‐Chool
Published: October 2002

The influence of ion implantation on the surface properties of polyimide was studied. We investigated microhardness, friction, wear and wettablility of polyimide. Energies of 50 keV and 200 keV were used, with doses ranging from 1 × 1013 to 1 × 1016 ion cm−2. The implanted ion species were B, N and Ar. The microhardness of polyimide increased after implantation for doses higher than 1 × 1015 ion cm−2. A reduction of the friction coefficient was in most cases correlated with a reduction of wear. The contact angles of water for B‐ and N‐implanted polyimide decreased, as the doses increased at energies of 50 keV and 200 keV. As time elapsed, the contact angle for B‐ and N‐implanted polyimide films gradually increased and finally approached the initial value under ambient room conditions. However, the contact angle of Ar‐ion‐implanted polyimide did not change under ambient room conditions, even after a few months had elapsed.

© 2002 Society of Chemical Industry
Dynamic mechanical analysis of an epoxy/thermoplastic blend: polymerization‐induced phase separation
Authors: López Joaquín , Ramírez Carmen , Abad María J , Barral Luis , Cano Jesús , Díez Francisco
Published: October 2002

Phase separation behaviour and analysis of the morphologies for a commercial epoxy resin based on tetraglycidyl‐4,4′‐diaminodiphenylmethane (TGDDM) with 4,4′‐diaminodiphenylsulfone (DDS) as hardener and blended with different amounts of poly(styrene‐co‐acrylonitrile) (SAN) thermoplastic, have been studied by dynamic mechanical analysis (DMA) supported by other techniques. In comparison with the neat system, the modified systems reach gelation and vitrification faster. These events have been assigned at the onset and the end of the storage modulus signals E′ in a DMA curve (E′ versus time). The results are explained by a phase‐separation phenomenon induced by polymerization. Scanning electron microscopy (SEM), focused on phase separation, has revealed a sea‐island type of morphology for low thermoplastic contents and an epoxy‐nodular or phase inverted structure for high thermoplastic contents.

© 2002 Society of Chemical Industry
Effects of NaCl on steady rheological behaviour in aqueous solutions of hydrophobically modified polyacrylamide and its partially hydrolyzed analogues prepared by post‐modification
Authors: Feng Yujun , Grassl Bruno , Billon Laurent , Khoukh Abdel , François Jeanne
Published: October 2002

The influences of NaCl on the steady rheological behaviour of aqueous solution were investigated for a hydrophobically modified polyacrylamide (HMPAM) and its hydrolyzed derivatives (HHMPAM) prepared by post‐modification. The apparent viscosity (ηapp) and reduced viscosity (ηred) were measured as a function of NaCl content. As salinity increased, ηred decreased for both HMPAM and HHMPAM in dilute regime; in the semidilute solution, a continuous increase of ηred was observed for HMPAM while ηred passed through a minimum in the case of HHMPAM. At a given polymer concentration in semidilute regime, both shear thickening and anti‐thixotropic properties were observed as a function of salinity and hydrolysis degree, as well as ageing time. Dilatancy was observed over a range of shear rates beyond which solutions behaved as classical polymer systems. When salinity exceeded a critical value, dilatancy and anti‐thixotropy appeared as increasing functions of ionic strength and decreasing functions of hydrolysis degree. Prolongation of ageing time strongly enhanced both shear thickening and anti‐thixotropic behaviors. These results are interpreted by the changes of the relative numbers of intra‐ and intermolecular associations, and the participation of free hydrophobes in the formation of clusters under shear.

© 2002 Society of Chemical Industry
Improvement of the mechanical properties of poly(D,L‐lactide) by orientation
Authors: Grijpma Dirk W , Altpeter Hanno , Bevis Michael J , Feijen Jan
Published: October 2002

Oriented, amorphous poly(D,L‐lactide) was obtained by drawing injection moulded specimens at temperatures below the glass transition temperature of the polymer and by a non‐conventional injection moulding process in which the melt is cooled under oscillating shear conditions (SCORIM). In both cases effective molecular orientation is achieved, allowing the preparation of degradable devices with much improved tensile properties and impact behaviour when compared to the non‐oriented material.

© 2002 Society of Chemical Industry
Direct visualization of microstructures in hydrophobically modified polyacrylamide aqueous solution by environmental scanning electron microscopy
Authors: Feng Yujun , Luo Pingya , Luo Chuanqiu , Yan Qituan
Published: October 2002

Environmental scanning electron microscopy (ESEM) is an improved technique which permits the observation of samples in their native state, requiring neither sample preparation nor surface coating, and so avoids losing the original characteristics of the observed specimens. By use of a differential pumping aperture system and a secondary electron detector, the environmental conditions in the sample chamber can be varied and accommodated to the properties of the samples. This newly developed technique is used in this work to characterize the microstructures of hydrophobically modified polyacrylamide (HMPAM) and its unmodified precursor in aqueous solution. The microstructures were directly visualized by sublimation of the ice in freeze‐dried samples. It is found that three‐dimensional network structures spread throughout the whole solution for both the modified and unmodified polymers when the polymer concentration is equal to or higher than the polymer critical association concentration (CAC); when the polymer concentration is below the CAC, a sparse network structure could be seen in the solutions of modified polymer, whereas no such phenomenon is found in unmodified polymer solutions. The network units of the microstructures in the solutions of modified polymer are displayed as regularly distributed hexagons, while those of unmodified polymer appear as irregular circles. The observed results are interpreted by a proposed association model.

© 2002 Society of Chemical Industry
Psychopharmacological profiles of Leucas Lavandulaefolia Rees
Authors: Mukherjee Kakali , Saha B. P. , Mukherjee Pulok K.
Published: October 2002

Methanol extract of Leucas lavandulaefolia (LLFE) was evaluated for different psychopharmacological profiles with various animal models in rats and mice. The extract showed a potential reduction in spontaneous activity and caused a significant decrease in exploratory behavioural pattern by the head dip and Y‐maze test. It also showed a significant reduction in muscle relaxant activity by rotarod, 30 ° inclined screen and traction tests. The extract showed a remarkable potentiation of pentobarbitone induced sleeping time in mice. Copyright © 2002 John Wiley & Sons, Ltd.
Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo‐controlled pilot study
Authors: Andreatini Roberto , Sartori Vânia A. , Seabra Maria L. V. , Leite José Roberto
Published: October 2002

The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates. Thirty‐six outpatients with generalized anxiety disorder (DSM III‐R), after a 2‐week wash‐out, were randomized to one of the following three treatments for 4 weeks (n = 12 per group): valepotriates (mean daily dose: 81.3 mg), diazepam (mean daily dose: 6.5 mg), or placebo. A parallel, double‐blind, flexible‐dose, placebo‐controlled design was employed. No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale (HAM‐A) or in the trait part of the state‐trait anxiety inventory (STAI‐trait). Moreover, the three groups presented a significant reduction in the total HAM‐A scores. On the other hand, only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM‐A. The diazepam group also presented a significant reduction of the STAI‐trait. Although the principal analysis (HAM‐A between group comparison) found negative results (probably due to the small sample size in each group), the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety. However, since the number of subjects per group was very small, the present results must be viewed as preliminary. Thus, further studies addressing this issue are warranted. Copyright © 2002 John Wiley & Sons, Ltd.
Antimutagenic effects of black tea (World blend) and its two active polyphenols theaflavins and thearubigins in Salmonella assays
Authors: Gupta S. , Chaudhuri T. , Seth P. , Ganguly D. K. , Giri A. K.
Published: October 2002

Almost two thirds of the world population consume tea everyday. Tea is processed differently in different parts of the world to give green (20%), black (78%) or oolong tea (2%). The antimutagenic and anticarcinogenic activities of green tea were extensively investigated compared with those of black tea. Considering the potent antimutagenic effects of green tea we recognized the need to evaluate the antimutagenic effects of black tea (World Blend Tea, Southern Tea Co., Marietta, GA) in Salmonella strains TA97a, TA98, TA100 and TA102 in preincubation tests, both with and without S9 activation. Attempts have also been made to compare the results of the tea extracts with their two active polyphenols theaflavins and thearubigins. Antimutagenicity assays were carried out in bacterial plates treated with different concentrations (1%, 2.5%, 5%, 10% and 20%) of tea extracts against known bacterial mutagens sodium azide, 4‐nitro‐o‐phenylenediamine, cumine hydroperoxide, 2‐aminofluorene and danthron. A significant decrease in the number of revertant colonies was observed in the plates treated with 1% to 20% of tea extract plus positive mutagen when compared with positive mutagen only. Both the active polyphenols theaflavins and thearubigins extracted from the black tea (World blend) also showed significant antimutagenic effects against known positive compounds in these strains. In the experiments with S9 activation, the antimutagenic effects were significantly higher. These results indicate that black tea and its two polyphenols have significant antimutagenic effects in Ames Salmonella assays. Copyright © 2002 John Wiley & Sons, Ltd.
Studies on the antiinflammatory activity of Betula alnoides bark
Authors: Sur Tapas Kumar , Pandit Srikanta , Battacharyya Dipankar , Kumar C. K. Ashok , Lakshmi S. Mohana , Chatttopadhyay D. , Mandal Subhash C.
Published: October 2002

The antiinflammatory activity of Betula alnoides extract was evaluated in acute and subacute inflammation models. The extract was also evaluated for antiinflammatory activity in sheep RBC induced sensitivity and in membrane stabilization models. Except for the sheep RBC induced sensitivity model, the extract showed significant antiinflammatory activity. Copyright © 2002 John Wiley and Sons, Ltd.
Studies on essential oils: Part 10; Antibacterial activity of volatile oils of some spices
Authors: Singh G. , Kapoor I. P. S. , Pandey S. K. , Singh U. K. , Singh R. K.
Published: October 2002

The essential oils extracted from the seeds of seven spices, Anethum graveolens, Carum capticum, Coriandrum sativum, Cuminum cyminum, Foeniculum vulgare, Pimpinella anisum and Seseli indicum have been studied for antibacterial activity against eight pathogenic bacteria, causing infections in the human body. It has been found that the oil of C. capticum is very effective against all tested bacteria. The oil of C. cyminum and A. graveolens also gave similar results. These oils are equally or more effective when compared with standard antibiotics, at a very low concentration. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of Gentiana lutea ssp. symphyandra on the Central Nervous System in Mice
Authors: Öztürk Nilgün , Can Başer K Hüsnü , Aydin Süleyman , Öztürk Yusuf , Çaliş Ihsan
Published: October 2002

A methanolic extact of Gentiana lutea ssp. symphyandra roots has been investigated for its possible effects on the central nervous system of mice. At doses of 250 and 500 mg/kg (i.p.), the methanol extract of Gentiana roots caused a significant increase in the swimming endurance test and exhibited slight analgesic activity, but no lethality in mice suggesting some activity on the central nervous system. However, there was no indication of sedation or muscular fatigue at the doses employed. HPLC analysis showed that three secoiridoid compounds, gentiopicroside, swertiamarine and sweroside were present and may have been responsible for the CNS effects of the methanol extract of Gentiana lutea ssp. symphyandra roots. Copyright © 2002 John Wiley & Sons, Ltd.
Screening of eight alkaloids and ten flavonoids isolated from four species of the genus Boronia (Rutaceae) for antimicrobial activities against seventeen clinical microbial strains
Authors: Nazrul Islam S. K. , Gray Alexander I. , Waterman Peter G. , Ahasan M.
Published: October 2002

Eight alkaloids and ten flavonoids isolated from four species of Boronia of the Rutaceae were screened against 17 clinical microbial strains. Of the test compounds, three acridone and one quinolone alkaloids and eight flavonoids were reported as novel natural products. Screening was carried out by the standard disc diffusion method. Of the tested compounds, six alkaloids and seven flavonoids including the novel products were active against six clinical strains. The active compounds showed mild to moderate activities against Bacillus subtilis, Staphylococcus aureus, Sarcina lutea, exterotoxigenic Escherichia coli, Salmonella typhi and Klebsiella sp. Of the active flavonoids, some exhibited fairly significant activity towards Staphylococcus aureus, Sarcina lutea, Salmonella typhi and Klebsiella sp. The flavonoids were observed to have higher spectrum and magnitude of activity than those of the alkaloids. A standard ampicillin disc was used to compare the results. Copyright © 2002 John Wiley & Sons, Ltd.
HIV viral load: the myth of the undetectable?
Authors: Pillay Deenan
Published: October 2002

There is a wealth of data supporting the use of viral load measurements to monitor therapy. Indeed, clinical drug trial endpoints routinely include the proportion of patients with a plasma viral load reduction of greater than 0.5 log10, or greater than 1 log10. Since a higher viral load reflects increased amounts of virus replication, it would seem desirable to reduce this replication as far as possible, so that the goal of therapy has become one of viral undetectability in plasma. However, virological suppression to undetectable levels is not an absolute determinant of outcome because recent observational cohort data suggest that any significant reduction of viral load is associated with clinical benefit. There are also technical problems when attempting to measure undetectability, with lower limits of detection of 400 or 50 RNA copies/ml of plasma being driven more by the performance of commercial assays than by any inherent cut‐off value with proven prognostic significance. Furthermore, the obsession with undetectability has created the concept of the ‘viral blip’, or ‘intermittent viraemia’ commonly defined as a single viral load measurement of between 50 and 400 copies/ml, preceded and followed by consistent measurements of less than 50 copies/ml, in a patient receiving therapy. Such blips should be considered in the context of frequent transient changes in viral load which occur below the lower limit of detection by existing laboratory assays. In my view, there remains a misunderstanding about the importance ascribed to these relatively minor changes in lower detection limits, when considered against the background of virus within the body as a whole. I also consider other possible uses of HIV‐1 quantification in clinical practice, such as identifying the inherent potency of antiviral regimens. Copyright © 2002 John Wiley & Sons, Ltd.
Environmental, economic and social effects caused by NAFTA in the fishery food companies of Baja California Sur, Mexico
Authors: Beltrán L. F. , Ortega‐Rubio A. , Lagunas M. , González H. , Soto M. , Acevedo M.
Published: October 2002

Even though the international trade system was originally developed without considering environmental protection, efforts are being made to join environmental and political aims. In Mexico, Baja California Sur (BCS) is the most arid state and that with the longest coastline. Efforts to insert BCS into the international market have usually reflected the environmental topic. The purpose of this work was to identify environmental, economic and social impacts caused by the North American Free Trade Agreement (NAFTA) in BCS. We analysed, from 1994 to the present, the main fishery companies for growth in production, increases in the quantities and value of export products, the participation of personnel in environmental aspects, changes in pollution prevention and control, new technology, increase of investments and generation of employment. We find that in the short and medium term, NAFTA in the fishery sector has had no significant effects on the environmental, economic and social variables studied. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
Development beyond markets, and bioregionalism
Authors: Rajeswar Jonnalagadda
Published: October 2002

Far more than technology‐oriented resource economics, development also involves ecological, institutional, cultural, traditional, intellectual, ethical and spiritual dimensions. Conventional economic indicators fail to even measure economic sustainability, let alone accurately reflect social and ecological aspects of sustainable development. Hence, it is highly essential to standardize the human and social development indicators, rather than, or in addition to, the integrated accounting framework in monetary and physical terms. Given the growth fixation in global economy, and the resulting environmental breakdown, the real battleground on which the ecological future of the planet will be decided is clearly a social one.

There has been an increasing ideological support for ‘bioregionalism’. The densely forested Eastern Ghats region of Andhra Pradesh in India, with its obvious eco‐political potential, offers a typical case for ‘bioregionalism’. The author has conducted extensive ethno‐ecological studies in the high altitude tribal area zone of the Eastern Ghats. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
Community strategies: mainstreaming sustainable development and strategic planning?
Authors: Williams Paul M.
Published: October 2002

New legislation places a statutory duty on all local authorities in England and Wales to prepare ‘community strategies’ for promoting the economic, social and environmental well‐being of their areas, and contributing to the achievement of sustainable development in the U.K. This paper suggests that community strategies herald the demise of the frequently marginalized Local Agenda 21 strategies and offers the prospect of mainstreaming the principles of sustainable development into the core of local governance.

However, the author argues that community strategies are unlikely to be effective if their preparation is grounded on the use of the rational or classical model of strategic management. A critical review is undertaken of this model and attention is especially drawn to a number of key inherent fallacies including spurious rationality, linear as opposed to nonlinear thinking, over‐formalization and a separation of the planning and operational elements of the process. The paper concludes with some thoughts on the potential contribution of alternative strategic management paradigms, and their implications for the preparation of community strategies. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
Relating functional requirements and software architecture: separation and consistency of concerns
Authors: Heckel R. , Engels G.
Published: October 2002

In the early stages of most software processes, functional and non‐functional (such as architectural, performance, or security) requirements are expressed separately in different sub‐models. Later these requirements have to be integrated into one overall system design. The integration raises consistency issues between different sub‐models, which have to be resolved in the process.

If requirements evolve over time, this leads to changes to the sub‐models concerned. Thus, new consistency issues arise between changed and unchanged sub‐models. In this case, a clear separation of concerns between different sub‐models is required to keep the effect of changes as local as possible.

In this paper, we use a relational approach to couple functional and architectural models while keeping them separated in order to simplify change. The approach uses meta modeling to support the static integration and concepts from the theory of graph transformation to formalize the semantic consistency of the dynamic aspects. Copyright © 2002 John Wiley & Sons, Ltd.
p90‐RSK and Akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant‐stimulated neutrophils
Authors: De Mesquita Dirson D. , Zhan Qian , Crossley Lisa , Badwey John A.
Published: October 2002

Stimulation of neutrophils with the chemoattractant fMet‐Leu‐Phe (fMLP) triggers phosphorylation/inactivation of the α‐ and β‐isoforms of glycogen synthase kinase 3 (GSK‐3) with phosphorylation of the α‐isoform predominating. These reactions were monitored with a phosphospecific antibody that only recognized the α‐ or β‐isoforms of GSK‐3 when these proteins were phosphorylated on serine residues 21 and 9, respectively. Inhibitor studies indicated that phosphorylation of GSK‐3α may be catalyzed by the combined action of p90‐RSK and Akt and may represent a new strategy by which G protein‐coupled receptors inactivate GSK‐3. Inactivation of GSK‐3 may be one of the mechanisms that delay apoptosis in fMLP‐stimulated neutrophils.
Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases
Authors: Pang Yuan-Ping , Xu Kun , Kollmeyer Thomas M. , Perola Emanuele , McGrath William J. , Green Dave T. , Mangel Walter F.
Published: October 2002

Using the computer docking program EUDOC, in silico screening of a chemical database for inhibitors of human adenovirus cysteine proteinase (hAVCP) identified 2,4,5,7‐tetranitro‐9‐fluorenone that selectively and irreversibly inhibits hAVCP in a two‐step reaction: reversible binding (K
i=3.09 μM) followed by irreversible inhibition (k
i=0.006 s−1). The reversible binding is due to molecular complementarity between the inhibitor and the active site of hAVCP, which confers the selectivity of the inhibitor. The irreversible inhibition is due to substitution of a nitro group of the inhibitor by the nearby Cys122 in the active site of hAVCP. These findings suggest a new approach to selective, irreversible inhibitors of cysteine proteinases involved in normal and abnormal physiological processes ranging from embryogenesis to apoptosis and pathogen invasions.
Transcriptional effect of hypoxia on placental leptin
Authors: Grosfeld Alexandra , Turban Sophie , André Jocelyne , Cauzac Michèle , Challier Jean-Claude , Hauguel-de Mouzon Sylvie , Guerre-Millo Michèle
Published: October 2002

We observed recently1 that placental leptin is markedly increased in preeclampsia. Since this disorder is associated with vascular disorders, we have tested the hypothesis that hypoxia regulates leptin expression. We show that hypoxia increased leptin mRNA and secretion in trophoblast‐derived BeWo cells. This effect was mediated through leptin promoter activation. 5′ deletion analysis allowed us to delineate two regions containing 1.87 kb and 1.20 kb of the promoter which conferred respectively high and low responsiveness to hypoxia. These data indicate that leptin is up‐regulated by hypoxia through a transcriptional mechanism likely to involve distinct hypoxia‐responsive cis‐acting sequences on the promoter.
Vesicovaginal fistula treated with fibrin glue
Authors: Kanaoka Y , Hirai K , Ishiko O , Ogita S
Published: October 2002

We report here a case of vesicovaginal fistula, following radiation therapy and intensive local chemotherapy for recurrent endometrial cancer of the vaginal stump, which was ameliorated with fibrin glue. The procedure temporarily postponed urinary diversion until the recurrence of irreparable fistula more than 4 years after the development of the first vesicovaginal fistula.
Evaluation of fetal femur length to detect Down syndrome in a Thai population
Authors: Tannirandorn Y. , Manotaya S. , Uerpairojkit B. , Tanawattanacharoen S. , Wacharaprechanont T. , Charoenvidhya D.
Published: October 2002

Objective: To assess the value of femur length shortening for prenatal detection of Down syndrome in a Thai population. Method: A prospective study was performed by experienced perinatologists on 3137 women undergoing second‐trimester amniocentesis, between 16 and 24 weeks of gestation, for the indications of advanced maternal age and past history of chromosomal abnormality. Biparietal diameter and femur length measurements were obtained before the procedures. Regression equations relating biparietal diameter to femur length were used to calculate observed femur length/expected femur length ratio in the chromosomally normal and Down syndrome fetuses. Sensitivity, specificity, false‐positive rate and likelihood ratio of a positive test result at various observed femur length/expected femur length ratios for detection of Down syndrome were calculated. A receiver–operator characteristic curve was used to determine threshold screening ratio. Results: There were 3084 chromosomally normal pregnancies, 26 fetuses with Down syndrome (1:118), and 27 other chromosomal abnormalities. The relationship between femur length and biparietal diameter (BPD) was: expected femur length=−7.631+0.814 BPD, R2=0.78, P<0.001). Femur length in Down syndrome fetuses was significantly shorter than in normal fetuses (P<0.001). A ratio of 0.91 for observed femur length/expected femur length yielded a sensitivity of 42.3%, specificity of 86.2%, false positive rate of 13.8% and likelihood ratio of a positive test result of 3.07 (95% CI 1.94–4.84) for detection of Down syndrome. Conclusions: In this study, femur length shortening in the second trimester appears to be a useful screening parameter for fetal Down syndrome in a Thai population.
Spectral analysis of fetal heart rate variability as a predictor of intrapartum fetal distress
Authors: Chung D.Y. , Sim Y.B. , Park K.T. , Yi S.H. , Shin J.C. , Kim S.P.
Published: October 2002

Objective: To evaluate the usefulness of power spectral analysis on fetal heart rate variability as a new diagnostic method of fetal distress. Study design: Among 76 pregnant women who underwent computerized electronic fetal monitoring and cord blood gas analysis, we divided them into three groups: normal fetus group (36); presumed distress group (26); and acidemic distress group (14). In order to perform linear analysis on the raw data of the fetal heart rate, after resampling, we performed Fourier transformation and investigated power distributions among very low frequency (VLF), low frequency (LF), high frequency (HF) bands, and autonomic balance (LF/HF). Results: The results of the spectral analysis showed that in normal fetus group, the difference in the distribution of power spectrums of VLF, LF and HF was significantly higher than in presumed distress group and acidemic distress group. In fetal distress, the LF and VLF value (≤0.0023, ≥0.0437) were good predictors (sensitivity 97.5%, 75.0% and specificity 86.1%, 94.4%). The LF value (≤0.0013) was a good predictor in fetal acidemia (sensitivity 97.5% and specificity 86.1%). Conclusions: A computerized spectral analysis of fetal heart rate variation is a good predictor of fetal distress, which is made automatically and objectively.
The management of severely malformed newborn infants: the case of conjoined twins
Authors: Dickens B.M , Cook R.J
Published: October 2002

The birth of ‘Siamese’ twins in August 2000 whose parents refused to consent to surgery for separation required English courts to decide whether the twins could lawfully be separated despite that refusal when one twin would certainly die as a direct surgical result. The Court of Appeal unanimously upheld the trial judge's decision to authorize surgery, taking account of principles of family law, criminal law and human rights law. Parental duties to the viable twin were found consistent with the justification of allowing, without intending, natural death of the non‐viable twin. The right to human dignity of both twins supported the justification of separation surgery. The decision did not elevate physicians’ choices over parents’, but subjected both to the law. The hospital was found entitled to bring the case to court, but not obliged; it could have declined surgery in conformity with the parents’ wishes.
Introduction to therapy of hepatitis C
Authors: Lindsay Karen L.
Published: October 2002

Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States.
Optimal therapy of hepatitis C
Authors: Di Bisceglie Adrian M. , Hoofnagle Jay H.
Published: October 2002

The highest response rates to antiviral therapy for the treatment of chronic hepatitis C have been achieved using the combination of peginterferon and ribavirin. Recently completed controlled trials have reported rates of sustained virological response (SVR) between 50% and 60% in patients treated with higher doses of peginterferon and ribavirin, which was 5% to 10% higher with standard doses of interferon alfa and ribavirin. The major determinant of outcome of therapy is hepatitis C virus (HCV) genotype. With the combination of peginterferon and ribavirin, patients with genotype 1 achieve response rates of 40% to 45%, compared with rates approaching 80% with genotypes 2 or 3. Importantly, patients with HCV genotype 1 achieve higher rates of response with 48 weeks than with 24 weeks of therapy, whereas patients with genotypes 2 and 3 are adequately treated with a 24-week course. Furthermore, patients with genotypes 2 and 3 require only 800 mg of ribavirin daily to achieve optimal response rates, whereas 1,000 to 1,200 mg daily is needed for patients with genotype 1. Future studies should focus on optimizing the dose of peginterferon and ribavirin by patient characteristics, particularly on resolving the issue of weight-based dosing. For patients with good prognostic factors, a lower dose and shorter course of peginterferon may be adequate for full effect. Importantly, research is needed to show how treatment regimens can best be applied to other patient groups with hepatitis C, such as patients with acute hepatitis, human immunodeficiency virus coinfection, renal disease, solid-organ transplant, neuropyschiatric disease, autoimmunity, and alcohol or substance abuse.
Hepatitis C and human immunodeficiency virus infection
Authors: Thomas David L.
Published: October 2002

In the United States, an estimated 200,000 persons are infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). As the lives of HIV-infected persons have been prolonged by use of highly active antiretroviral therapy, liver disease has emerged as an important, and in some settings, the leading cause of morbidity and mortality. Human immunodeficiency virus infection appears to adversely affect all stages of hepatitis C infection, leading to increased viral persistence and accelerated progression of HCV-related liver disease. In turn, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity caused by antiretroviral medications. The medical management of hepatitis C in HIV-infected persons remains controversial, in part because of the complexity of both infections and potential drug interactions, but chiefly because there is so little published information. Nonetheless, the burden of liver disease is too high to delay management of HIV/HCV-coinfected persons while awaiting better data. Instead, the management of hepatitis C today must be based on data generated on persons without HIV and an understanding of both infections. Properly designed studies of therapy in HIV/HCV-coinfected persons are needed to help guide management of these patients in the future.
Treatment of patients with hepatitis C and normal serum aminotransferase levels
Authors: Bacon Bruce R.
Published: October 2002

Approximately 30% of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels and another 40% have ALT levels that are less than twice the upper limit of the normal range. Most patients with normal ALT levels have mild degrees of inflammation with mild or no fibrosis, and the rate of disease progression is reduced compared with that in patients with elevated ALT levels. Some patients with normal ALT levels have advanced fibrosis and cirrhosis on liver biopsy. Treatment of patients with normal ALT levels with either interferon monotherapy or interferon/ribavirin combination therapy has shown sustained virological response (SVR) rates that are equivalent to those achieved for patients with elevated ALT levels. Thus, patients with chronic hepatitis C should not be excluded from therapy based on ALT levels alone. The decision to initiate therapy with interferon and ribavirin should be based on a combination of factors independent of ALT levels including amount of fibrosis on liver biopsy, hepatitis C virus (HCV) genotype and viral level, patient age and motivation, and co-morbid illness, and the presence of other complicating conditions.
Prevention of spread of hepatitis C
Authors: Alter Miriam J.
Published: October 2002

Hepatitis C virus (HCV) is transmitted by percutaneous or permucosal exposure to infectious blood or blood-derived body fluids. Based on the results of cohort and acute case control studies, risk factors associated with acquiring HCV infection in the United States have included transfusion of blood and blood products and transplantation of solid organs from infected donors, injecting drug use, occupational exposure to blood (primarily contaminated needle sticks), birth to an infected mother, sex with an infected partner, and multiple heterosexual partners. Nosocomial and iatrogenic transmission of HCV primarily are recognized in the context of outbreaks, and primarily have resulted from unsafe injection practices. Transmission from HCV-infected health care workers to patients is rare. Transfusions and transplants have been virtually eliminated as sources for transmission, and most (68%) newly acquired cases of hepatitis C are related to injecting drug use. The primary prevention of illegal drug injecting will eliminate the greatest risk factor for HCV infection in the United States. Other prevention strategies that need to be widely implemented include risk reduction counseling and services and review and improvement of infection control practices in all types of health care settings. Testing for HCV infection should be routinely performed for persons at high risk for infection or who require postexposure management. There are no recommendations for routine restriction of professional activities for HCV-infected health care workers, and persons should not be excluded from work, school, play, and child care or other settings on the basis of their HCV infection status.
Monitoring of viral levels during therapy of hepatitis C
Authors: Davis Gary L.
Published: October 2002

Alpha interferon therapy of chronic hepatitis C is typically accompanied by a biphasic decrease in hepatitis C virus (HCV) RNA levels: an initial rapid decline during the first 24 to 48 hours, and a second more gradual decline during the following weeks. The rate of second-phase decline correlates with ultimate response to interferon treatment. Thus, assessment of early virological response (EVR) may predict outcome. Data from 2 large clinical trials of peginterferon and ribavirin were combined and analyzed to determine the optimal definition of an EVR which, if not achieved, was associated with a low likelihood of a sustained virological response (SVR). A fall in HCV RNA level to undetectable or by at least 2 log10 units after 12 weeks was found to be the optimal definition of an EVR. Among 965 patients, 778 (80%) achieved an EVR by week 12, including all except 1 patient with genotypes 2 or 3. Among 187 patients without an EVR, only 3 (1.6%) had an SVR. These findings suggest that patients with genotype 1 who do not achieve an EVR should stop treatment after 12 weeks. Use of an early stopping rule reduces treatment costs by at least 16% and avoids the inconvenience and side effects of treatment in the 19% of patients without an EVR who have little chance of a lasting virological response.
Natural history of chronic hepatitis C
Authors: Seeff Leonard B.
Published: October 2002

Much controversy surrounds the issue of the natural history of hepatitis C virus (HCV) infection. Many authorities view the disease as inexorably progressive with a high probability of advancing over time to cirrhosis and occasionally hepatocellular carcinoma (HCC) and, therefore, likely to be responsible for causing death. Others regard chronic hepatitis C as having a variable outcome, the majority of infected persons not dying from the disease, but more likely from the comorbid conditions that so often accompany infection by this agent, or from more common medical conditions. Disagreements probably derive from the manner of conduct of the study and the populations studied. Efforts to determine natural history are handicapped by the primary characteristics of the disease, namely that its onset rarely is recognized and its course is prolonged exceedingly. Thus, different outcomes have come from retrospective rather than from prospective studies, but both have concluded that at least 20% of chronically infected adults develop cirrhosis within 20 years. More recent studies that used a retrospective/prospective approach, focusing largely on young infected individuals, have produced different results. Among these young people, particularly young women, spontaneous resolution of the viral infection is more common than previously thought and cirrhosis has been identified in 5% or fewer of them. The major failing for all groups studied, young and old, is that natural history studies have rarely exceeded the first 2 decades, so that outcome beyond this time is not known, other than through modeling. Several host-related and extraneous factors probably affect the natural history.
Therapy of acute hepatitis C
Authors: Alberti Alfredo , Boccato Silvia , Vario Alessandro , Benvegnù Luisa
Published: October 2002

Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover.
Side effects of therapy of hepatitis C and their management
Authors: Fried Michael W.
Published: October 2002

Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
Retreatment of patients with chronic hepatitis C
Authors: Shiffman Mitchell L.
Published: October 2002

Significant advances have been made in the treatment of chronic hepatitis C virus (HCV) infection during the past 5 years. As a consequence, there is continuing enthusiasm for retreating patients who did not achieve sustained virological response (SVR) with previous therapy. Retreatment of non-responders to standard interferon monotherapy using interferon and ribavirin has yielded SVR rates of 12% to 15%. Retreatment with peginterferon and ribavirin has been more effective; achieving SVR rates of 34% to 40%. Retreatment of patients who relapsed after interferon monotherapy using standard interferon and ribavirin yielded SVR rates of 47%, whereas retreatment with peginterferon and ribavirin resulted in an SVR rate of about 60%. The major factors associated with a higher likelihood of an SVR after retreatment include previous relapse, previous treatment with interferon monotherapy, HCV genotypes 2 or 3, lower serum levels of HCV RNA, and having a significant decrease in HCV RNA levels during the initial course of therapy. These results help to focus retreatment with peginterferon and ribavirin on subsets of patients who are most likely to benefit.
Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review
Authors: Gebo Kelly A. , Chander Geetanjali , Jenckes Mollie W. , Ghanem Khalil G. , Herlong Franklin H. , Torbenson Michael S. , El-Kamary Samer S. , Bass Eric B.
Published: October 2002

This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to 100%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes.