bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐effectiveness analysis of two strategies for mass screening for colorectal cancer in France
Authors: Berchi Célia , Bouvier Véronique , Réaud Jean‐Marie , Launoy Guy
Published: February 2004

The implementation of colorectal cancer mass screening is a high public health priority in France, as in most other industrialised countries. Despite evidences that screening using guaiac fecal occult blood test may reduce colorectal cancer mortality, no European country has organised widespread mass screening with this test. The low sensitivity of this test constitutes its main limitation. Immunological tests, which provide higher sensitivity than the guaiac test, may constitute a satisfactory alternative. This study was carried out to compare the costs and the effectiveness of 20 years of biennial colorectal cancer (CRC) screening with an automated reading immunological test (Magstream) with those obtained with a guaiac stool test (Haemoccult).

The model used to estimate the costs and effectiveness of successive biennial CRC screening campaigns was a transitional probabilistic model. The parameters used in this model concerning costs and CRC epidemiological data were calculated from results obtained in the screening program run in Calvados or from published results of foreign studies because of the lack of French studies.

The use of Magstream for 20 years of biennial screening costs 59 euros more than Haemoccult per target individual, and should lead to a mean increase in individual life expectancy of 0.0198 years (i.e. about one week), which corresponds to an incremental cost‐effectiveness ratio of 2980 euros per years of life saved.

Our results suggest that using an immunological test could increase the effectiveness of CRC screening at a reasonable cost for society. Copyright © 2003 John Wiley & Sons, Ltd.
Overall versus socioeconomic health inequality: a measurement framework and two empirical illustrations
Authors: Wagstaff Adam , Doorslaer Eddy van
Published: February 2004

This paper outlines a framework for comparing empirically overall health inequality and socioeconomic health inequality. The framework, which is developed for both individual‐level data and grouped data, is illustrated using data on malnutrition amongst Vietnamese children and on health utility amongst Canadian adults. In both cases, the degree of socioeconomic inequality is estimated at around 25% of overall inequality. Copyright © 2003 John Wiley & Sons, Ltd.
Empirical assessment of the economic behaviour of Dutch general hospitals
Authors: Blank J.L.T. , Merkies A.H.Q.M.
Published: February 2004

We study the cost structure and efficiency of Dutch general hospitals over the period 1985–1995. Several studies on the efficiency of hospitals now exist. Most of them start from the assumption that hospital management attempts to minimize cost. We went beyond this assumption by trying to collect empirical evidence on management behaviour with respect to patient selection. We did so by estimating both the direct cost function and the indirect cost function as proposed by Färe and Primont and compared the results. We found that acknowledging the possibility of output reallocation increases the validity of optimizing models in the hospital sector but a complete indirect optimizing model ignores that some output categories are less flexible especially in the short run. Endogenous shifts in the allocation of patients appear to be realized through time by increased specialization of hospitals. We suggest that a mixed direct–indirect cost model is probably preferable. Copyright © 2003 John Wiley & Sons, Ltd.
A multi‐method approach to measuring health‐state valuations
Authors: Salomon Joshua A. , Murray Christopher J.L.
Published: February 2004

Existing techniques for eliciting health‐state valuations incorporate both strength of preferences for health states and other values such as risk aversion or time preference. This paper presents a new methodological approach that allows estimation of a set of core underlying health‐state values based on responses elicited through multiple measurement techniques. A study was undertaken in which respondents completed the visual analogue (VAS) scale, time trade‐off (TTO), standard gamble (SG) and person trade‐off (PTO) for a range of states. By specifying flexible parametric functions to explain responses on each measurement technique, we estimated both the underlying strength of preference values for the health states in the study and the values for a set of auxiliary parameters characterising risk attitudes, discount rates, distributional concerns and scale distortion effects in the group of respondents. This study demonstrates that it is possible to understand responses on these four different measurement techniques based on a consistent set of core values. The approach presented here can provide insights into different sources of observed variation in VAS, TTO, SG and PTO responses and facilitate appropriate adjustment of valuations elicited through different methods for use in summary health measures and economic analyses. Copyright © 2003 John Wiley & Sons, Ltd.
Technological developments and applications in clinical psychology and psychotherapy: Introduction
Authors: Caspar Franz
Published: February 2004

This article introduces a special issue on technological developments and applications in clinical psychology and psychotherapy. The question of why it is important to deal with such developments is raised. An overview of the individual topics and articles in the issue is given, and additional aspects are discussed. This is followed by an overview of possible advantages and disadvantages of technological developments as well as problems to be solved. Overall, the developments are still largely underresearched, but—if utilized—hold considerable promise in changing the field of clinical psychology and psychotherapy as well as training in the field. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Computer treatment for common mental health problems
Authors: Cavanagh Kate , Shapiro David A.
Published: February 2004

Perhaps the most complex and controversial role for the computer in clinical practice is as a treatment medium in which the computer effectively replaces the psychotherapist. This article outlines the historical development of computer treatment, from dialogue generators in the 1960s through to the interactive, multimedia programs of the 2000s. In evaluating the most recent developments in computer treatment, we present a small meta‐analytic study demonstrating large effect sizes in favor of computer treatments for anxiety and depression for pre/post outcomes and treatment as usual/waitlist comparators. Next, we review studies of the cost effectiveness of computer treatments. Finally, we outline the implications for research, policy, and practice of this new generation of treatment options. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Computer‐supported cognitive behavioral treatment of anxiety disorders
Authors: Anderson Page , Jacobs Carli , Rothbaum Barbara O.
Published: February 2004

This article reviews the empirical literature pertaining to the use of computer‐supported cognitive‐behavioral treatment of anxiety disorders, including palmtop computers, virtual reality exposure therapy, and personal computer software programs. The advantages and disadvantages unique to each type of technology are described. The review concludes with a discussion of ethical issues, barriers to the use of technology by clinicians, and suggestions for a process by which scientists and practitioners can conceptualize how technology can advance our understanding of anxiety and our dissemination of effective treatments. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Online therapy: Review of relevant definitions, debates, and current empirical support
Authors: Rochlen Aaron B. , Zack Jason S. , Speyer Cedric
Published: February 2004

The current article reviews the most recent literature addressing the definitions, ethical considerations, and potential strengths and limitations of online therapy. In addition, a framework is provided for how to conceptualize and categorize different aspects of online therapy for research purposes. Relevant studies of both online and face‐to‐face therapy as well as suggestions for future research are outlined. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Computer‐supported monitoring of patient treatment response
Authors: Percevic Robert , Lambert Michael J. , Kordy Hans
Published: February 2004

The use of information technology (IT) for the purpose of improving psychotherapy outcomes in the context of routine clinical practice is described. IT efforts from two research programs, one in Germany and the other in the United States, are based on evidence that not all patients who enter treatment have a positive outcome and that continuous monitoring of patient treatment response with immediate feedback to therapists can be used to increase the likelihood of success for the poorly responding client. Such monitoring and feedback can best be accomplished by IT methodologies. Suitable IT systems are described, and their strengths and limitations are highlighted. Evidence is presented that supports the positive value of such efforts for improving patient treatment response. © 2004 Wiley Periodicals, Inc. J Clin Psychol 60: 285–299, 2004.
Computer‐based technological applications in psychotherapy training
Authors: Berger Thomas
Published: February 2004

Despite obvious and documented advantages of technological applications in education, psychotherapy training based on information technology is either still rare or limited to technical innovations such as videotape recordings. This article outlines opportunities new computer‐based learning technology create for psychotherapy training. First, approaches that include computer‐mediated communication between trainees and teachers/supervisors are presented. Then, computer‐based learning technology for self‐study purposes is discussed in the context of educational approaches to learning. Computer‐based tools that have been developed and evaluated in the context of psychotherapy training are described. Evaluations of the tools are discussed. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Virtual reality in psychotherapy training
Authors: Beutler Larry E. , Harwood T. Mark
Published: February 2004

Virtual reality (VR) has myriad applications to psychotherapy training and has manifold adjunctive or primary applications to psychotherapeutic treatments. Unfortunately, VR technology has not yet advanced to a point where many of these applications are readily available or even affordable; however, alternatives are available, and the creative investigator may build upon existing, available, and affordable technology to develop simple VR systems. Eventually, more sophisticated equipment and design features that increasingly approximate the VR three‐dimensional emersion environments may be added in a stepwise fashion to create more realistic iterations of the VR psychotherapeutic environment. In our initial VR training endeavor, elements of the empirically supported and multifaceted Systematic Treatment Selection model (STS, Beutler & Clarkin, 1990; Beutler, Clarkin, & Bongar, 2000; Beutler & Harwood, 2000) were chosen as training criteria and incorporated into our VR training system to demonstrate both its feasibility and practicality. This article outlines our initial endeavor in the development of a VR system for training in psychotherapy and summarizes STS training‐relevant research findings. Future directions for the applications of VR technology to both training and treatment are provided. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Computers in clinical assessment: Historical developments, present status, and future challenges
Authors: Butcher James N. , Perry Julia , Hahn Jungwon
Published: February 2004

Computerized testing methods have long been regarded as a potentially powerful asset for providing psychological assessment services. Ever since computers were first introduced and adapted to the field of assessment psychology in the 1950s, they have been a valuable aid for scoring, data processing, and even interpretation of test results. The history and status of computer‐based personality and neuropsychological tests are discussed in this article. Several pertinent issues involved in providing test interpretation by computer are highlighted. Advances in computer‐based test use, such as computerized adaptive testing, are described and problems noted. Today, there is great interest in expanding the availability of psychological assessment applications on the Internet. Although these applications show great promise, there are a number of problems associated with providing psychological tests on the Internet that need to be addressed by psychologists before the Internet can become a major medium for psychological service delivery. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Technological developments and applications in clinical psychology and psychotherapy: Summary and outlook
Authors: Caspar Franz
Published: February 2004

The current state as described in the articles in this special issue is summarized. Fascinating possibilities exist, and technical applications have a potential for making a contrbution back to underlying concepts, but a critical overview also reveals gaps, not only from a scientific perspective. We are warned of a use of “empty technology.” An outlook for great possible developments comes with a postulate of keeping the cost‐benefit ratio in mind. © 2004 Wiley Periodicals, Inc. J Clin Psychol.
Testicular morphological changes during the seasonal reproductive cycle in the bullfrog Rana catesbeiana
Authors: Sasso‐Cerri Estela , De Faria Flávio P. , Freymüller Edna , Miraglia Sandra M.
Published: February 2004

Spermatogenesis and steroidogenesis undergo seasonal variations during the reproductive cycle in amphibians. Testicular morphological and morphometric seasonal variations as well as interstitial lipidic inclusions and intralobular glycoconjugates were evaluated during seasonal cycle of Rana catesbeiana. Testes of frogs collected during the annual seasons were weighed for calculation of GSI (Gonadosomatic index). Seminiferous lobule diameters (DSL) and volume densities of seminiferous lobules (VvSL), excretory ducts (VvED), and interstitial tissue (VvIT) were analyzed. Semithin sections were submitted to Periodic Acid‐Schiff (PAS) and Alcian Blue (AB) methods for detection of glycoconjugates, while lipidic inclusions were detected by Sudan Black B. GSI showed no significant variations during the year. Since VvED and VvIT increased significantly during summer and were inversely proportional to VvSL, a compensatory effect between the testicular compartments may be related to the maintenance of GSI. During autumn/winter, larger lobular diameters were observed in comparison to spring/summer when spermiogenesis and spermiation were commonly observed. The increased VvIT and the numerous lipidic inclusions in the interstitial cells during summer suggest a relationship between spermiogenesis and steroidogenesis. Besides the structural stability variations occurring in the IT and SL, a possible paracrine interaction between ED and IT should be also involved in the IT development during summer. The presence of PAS and AB‐positive globular structures were observed in the seminiferous lobules and excretory ducts. These structures containing acid glycoconjugates appear to be Sertoli cell apical portions, which are accumulated in the lumen of the seminiferous lobules mainly during spermiation. J. Exp. Zool. 301A:249–260, 2004. © 2004 Wiley‐Liss, Inc.
Genome resource for the indonesian coelacanth, Latimeria menadoensis
Authors: Danke Joshua , Miyake Tsutomu , Powers Thomas , Schein Jacqueline , Shin Heesun , Bosdet Ian , Erdmann Mark , Caldwell Roy , Amemiya Chris T.
Published: February 2004

We have generated a BAC library from the Indonesian coelacanth, Latimeria menadoensis. This library was generated using genomic DNA of nuclei isolated from heart tissue, and has an average insert size of 171 kb. There are a total of 288 384‐well microtiter dishes in the library (110,592 clones) and its genomic representation is estimated to encompass ≥7X coverage based on the amount of DNA presumably cloned in the library as well as via hybridization with probes to a small set of single copy genes. This genomic resource has been made available to the public and should prove useful to the scientific community for many applications, including comparative genomics, molecular evolution and conservation genetics. J. Exp. Zool. 301A:228–234, 2004. © 2004 Wiley‐Liss, Inc.
Gravitational effects on apoptosis of presumptive ectodermal cells of amphibian embryo
Authors: Komazaki Shinji
Published: February 2004

The effects of simulated microgravity (clinostat rotation at 6 rpm) on the presumptive ectodermal cells of amphibian embryos were examined. When morulae of Cynops pyrrhogaster developed under the influence of simulated microgravity, the thickness of the presumptive ectoderm was greater significantly. Embryonic cells isolated from the presumptive ectoderm of morulae were cultured for one day under the influence of simulated microgravity. The number of cells was greater after such clinostat rotation than in the control culture. TUNEL staining and electron microscopy revealed apoptotic cells both in embryos and among cultured cells, but the number of apoptotic cells was smaller in clinostat‐treated embryos and cultured cells than in their controls. These results suggest that simulated microgravity suppresses apoptosis in the amphibian embryo, and as a result, affects the thickness of the presumptive ectoderm. J Exp Zool 301A:204‐211, 2004. © 2004 Wiley‐Liss, Inc.
Hepatopancreas gluconeogenesis during anoxia and post‐anoxia recovery in Chasmagnathus granulata crabs maintained on high‐protein or carbohydrate‐rich diets
Authors: Oliveira Guendalina T. , Eichler Paula , Rossi Isabel Cristina , Da Silva Roselis S. M.
Published: February 2004

C. granulata is a semiterrestrial crab that lives in the mesolittoral and the supralittoral zones of estuaries and faces hypoxia and anoxia when exposed to atmospheric air. The carbohydrate or protein content of the diets administered to the crabs induced different metabolic adjustments during anoxia and post‐anoxia recovery period. During the first hour in anoxia a marked increase in L‐lactate concentration in hemolymph was induced, followed by a reduction in its levels accompanied by two peaks in hepatopancreas gluconeogenic capacity. Anoxia exposure did not induce a reduction in the hepatopancreas phosphoenolpyruvate carboxykinase activity in either dietary group. Our results suggest that in anaerobiosis this crab uses the conversion of lactate to glucose in hepatopancreas to maintain the acid‐base balance and the glucose supply. In post‐anoxia recovery, the fate of L‐lactate is the hepatopancreas gluconeogenesis in high protein maintained crabs. On the other hand, in the crabs maintained on carbohydrate‐rich diet the L‐lactate levels decreased gradually in the hemolymph during the post‐anoxia recovery; however, the hepatopancreas gluconeogenesis did not increase. In both dietary groups, an increase in the gluconeogenic capacity of hepatopancreas occurred at 30 h of post‐anoxia recovery. J. Exp. Zool. 301A:240‐248, 2004. © 2004 Wiley‐Liss, Inc.
Expression of Aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes
Authors: Suzuki Aya , Tanaka Minoru , Shibata Naoki
Published: February 2004

In teleost fish, several studies have implicated estrogens in the process of ovarian development, but the exact role of endogenous estrogen is still unclear. We examined the expression of aromatase mRNA with in situ hybridization, and the effects of Fadrozole, a nonsteroidal aromatase inhibitor (AI), during ovarian development in medaka Oryzias latipes. Medaka aromatase was first detected on the ventral side of ovaries from four to 10 days after hatching (dah), after occurrence of oogenesis. AI treatment after hatching suppressed the ovarian cavity formation from 30 dah but did not affect early oogenesis and folliculogenesis during ovarian development. These results suggest that endogenous estrogen is specifically required for formation of the ovarian cavity, but is not essential for early oogenesis and folliculogenesis in medaka. J. Exp. Zool 301A:266–273, 2004. © 2004 Wiley‐Liss, Inc.
Lactation under induced five‐month delay reproduction in Iberian red deer (Cervus elaphus hispanicus)
Authors: Landete‐Castillejos T. , Garcia A. , Gómez J. A. , Berruga M. I. , Gallego L.
Published: February 2004

In Iberian deer, calf birth date affects both milk production and composition, as well as the weight change of hind during lactation and calf growth. This study examines a five‐month induced delay in calving (autumn group) in a group of 19 Iberian hinds compared to a group of 13 standard calving hinds (spring group). Fertility in the autumn group was half that of the spring one. From the former, a further two calves out of six died before or soon after birth. Successfully lactating hinds showed a greater concentration in protein, fat and lactose (P < 0.001), but did not differ from spring group in total milk yield, calf gain or weight change of hinds during lactation. However, after correcting for the greater calf or hind body weight at calving of the autumn group, this group showed lower values for these variables than the spring group. Results show that at least in Iberian deer, counter‐season reproduction is possible, and that the effects on lactation variables are similar to those of a natural delay in calving. J Exp Zool 301A:261‐‐265, 2004. © 2004 Wiley‐Liss, Inc.
Ionic strength and the polyvalent cation receptor of shark rectal gland and artery
Authors: Fellner Susan K. , Parker Laurel
Published: February 2004

The dogfish shark Squalus acanthias regulates plasma osmolality and extracellular volume by secreting a fluid from its rectal gland which has a higher NaCl and lower urea concentration than plasma. We have previously identified the presence of a calcium‐sensing receptor or polyvalent cation sensing receptor (CaSR) on vascular smooth muscle of the rectal gland artery (RGA) and rectal gland tubules (RGT). Activity of the CaSR is influenced by changes in ionic strength. This led us to speculate that the ingestion of invertebrate sea animals increased plasma ionic strength, resulting in inhibition of the receptor, relaxation of RGA, and reversal of inhibition of chloride secretion by the RGT. In contrast, ingestion of fish could diminish ionic strength and have the opposite effect. To study the effect of changes in extracellular ionic strength, shark Ringers solutions were adjusted to three different ionic strengths with NaCl, but the osmolarities were kept constant by varying the concentration of urea. High ionic strength inhibited and low ionic strength enhanced the response to increasing external Ca2+ from 2.5 to 4.7 mM in RGT. The increase in cytosolic Ca2+ ([Ca2+]i) of cells in low, normal, and high ionic strength Ringers solution was 344 ± 60, 201 ± 26, and 114 ± 15 nmol/L, respectively. The [Ca2+]i responses of RGA to external Ca2+ in Ringers of three different ionic strengths were 323 ± 43, 231 ± 14, and 56 ± 11 nmol/L, respectively. Activation of the CaSR by spermine was reduced by more than 50% by high ionic strength in both RGT and RGA. Whether the small changes in shark plasma ionic strength that occur after a shark ingests marine animals with lower and higher ionic strength modulates salt secretion by the rectal gland is not yet known. J. Exp. Zool. 301A:235–239, 2004. © 2004 Wiley‐Liss, Inc.
A non‐invasive method for assessing adrenal activity in the chinchilla (chinchilla lanigera)
Authors: Ponzio Marina F. , Monfort Steven L. , Busso Juan M. , Dabbene Viviana G. , Ruiz Rubén D. , De Cuneo Marta Fiol
Published: February 2004

The Chinchilla is a rodent that was once abundant in the central Andes of South America. Excessive hunting for fur greatly reduced its distribution at the beginning of the twentieth century, and today Chinchilla species are nearly extinct in the wild. Although protected, wild populations of chinchilla are still declining. In general, this species has received little research attention and its biology is poorly understood. Improvements in captive breeding, husbandry, and genetic management are needed to ensure the conservation of the species. In this study, a noninvasive corticosteroid hormone monitoring technique was validated for use in Chinchilla lanigera. Two male domestic chinchillas were administered 3H‐corticosterone (i.m.) to determine the time course and relative proportion of urinary and fecal steroid metabolites. Most radioactivity was detected in urine and feces 5–10 and ∼30 h post‐isotope administration, respectively. Corticosteroid immunoreactivity was assessed by corticosterone radioimmunoassay (RIA) and cortisol enzyme immunoassay (EIA). High‐pressure liquid chromatography (HPLC) separation of corticosteroid metabolites in unprocessed urine revealed the presence of highly polar corticosteroid metabolites, but after enzymatic hydrolysis and diethyl ether extraction, most immunoreactivity co‐eluted with unconjugated cortisol. A ‘cause‐and‐effect’ relationship between the administration of exogenous adrenocorticotrophic hormone (ACTH), and the appearance of increased urinary corticosteroid metabolites demonstrated the physiological relevance of these measures for evaluating adrenal status in male chinchillas. From a conservation perspective, these methods can aid in situ and ex situ initiatives designed to evaluate how environmental conditions and management strategies affect overall animal health, well‐being and reproduction. J. Exp. Zool. 301A:218–227, 2004. © 2004 Wiley‐Liss, Inc.
Temporal expression of thyroid hormone receptor α1 in the liver of the lizard Podarcis sicula
Authors: Virgilio Francesca , Sciarrillo Rosaria , De Falco Maria , Comitato Raffaella , Laforgia Vincenza , Varano Lorenzo , Cardone Anna
Published: February 2004

The effects of thyroid hormones on metabolism and development are mediated by thyroid hormone receptors (TRs). To gain a better understanding of the potential role of thyroid hormone receptors in the liver of the lizard Podarcis sicula, we have evaluated the expression of TRs during the more critical periods of the annual variations of thyroid activity. The results obtained have indicated that in the liver of the lizard P. sicula there are three transcripts: mRNA of 5.0 kb for TRα1, mRNA of 2.6 kb for TRα2, and 6.0 kb band, which represent unprocessed heteronuclear RNA, encoding unspliced primary transcripts of RNA prior to their processing into the mature TRα1 and TRα2. By means of slot‐blot, we are able to determine that there is a change in the expression of TRs that occurs in the liver during the annual cycle of thyroid activity. A major expression registers in May, when the lizard thyroid gland shows the maximal activity. The combination of molecular biology with immunohistochemistry revealed that hepatic cells were also TRα IR positive. Particularly intense immunostaining was present in the cell nuclei of animals sacrified in May. These observations suggest that in lizard P. sicula the thyroid hormone (T3) might regulate hepatic activity, modulating TR mRNA levels. J. Exp. Zool. 301A:212–217, 2004. © 2004 Wiley‐Liss, Inc.
Are enterovirus infections a co‐factor in sudden hearing loss?
Authors: Mentel Renate , Kaftan H. , Wegner U. , Reißmann A. , Gürtler L.
Published: February 2004

Since viral infections are believed to be one of the causes of sudden hearing loss we have used serological assays for herpes simplex virus (HSV), varicella zoster virus (VZV), and enterovirus as well as polymerase chain reaction for enterovirus to test 55 sudden hearing loss patients for viral infections. Serological screening of these patients for HSV and VZV failed to reveal significant differences between the patient group and the controls. In contrast, enterovirus sequences were detected by RT‐PCR in 40% of the patient group, but in none of the controls, suggesting that enterovirus infections may be associated with sudden hearing loss. J. Med. Virol. 72:625–629, 2004. © 2004 Wiley‐Liss, Inc.
Possible involvement in oncogenesis of a single base mutation in an internal ribosome entry site of Epstein–Barr nuclear antigen 1 mRNA
Authors: Endo Rika , Kikuta Hideaki , Ebihara Takashi , Ishiguro Nobuhisa , Kobayashi Kunihiko
Published: February 2004

It has been reported recently that the U leader exon located within the 5′ untranslated region of Epstein–Barr nuclear antigen 1 (EBNA1) gene contains an internal ribosome entry site (IRES) element. Sequence analysis of the U leader exon was undertaken in samples from 19 patients with infectious mononucleosis and 19 patients with lethal lymphoproliferative diseases and in 15 spontaneously established lymphoblastoid cell lines. The sequence was conserved except for a single base substitution (T‐C) at position 67,585. Although the mutation was detected in only one case of infectious mononucleosis, it was found in more than half of the lethal lymphoproliferative diseases and all lymphoblastoid cell lines. The results suggest that a mutation in the IRES element affects EBNA1 gene expression at the translational level and provides Epstein–Barr virus (EBV)‐infected cells with a growth advantage, leading to immortalization of cells in vitro and to the development of lethal lymphoproliferative diseases in vivo. J. Med. Virol. 72:630–634, 2004. © 2004 Wiley‐Liss, Inc.
Sustained CD8+ T‐cell immune response to a novel immunodominant HLA‐B*0702‐associated epitope derived from an Epstein–Barr virus helicase‐primase‐associated protein
Authors: Turčanová Vanda , Höllsberg Per
Published: February 2004

Generation of a peptide‐based vaccine against persistent viral infections, such as Epstein–Barr virus (EBV), requires identification of immunodominant epitopes recognized by anti‐viral cytotoxic T‐cells. Using available computer algorithms, we have screened the entire translated EBV genome for potential HLA‐B7‐binding peptides. The binding to HLA‐B7 of 18 selected peptides was assessed by competitive binding assays and was found to correlate with the computer‐assigned scores, confirming the predictive value of these algorithms in selection of HLA‐B7‐associated peptides. Screening of the immune responses to these peptides by ELISpot assays identified a novel immunodominant epitope, termed LPRA, derived from an EBV helicase‐primase‐associated protein encoded by BBLF2/3. Peptide‐specific cells constituted up to 0.8% LPRA‐specific CD8+ T‐cells in the matured anti‐viral response. Cytotoxic and proliferative cytotoxic T lymphocytes (CTL) responses to the LPRA peptide were readily demonstrated ex vivo. In addition, mutational studies of this epitope demonstrated a highly specific recognition by LPRA‐specific CD8+ T‐cells. Taken together, our data suggest that the novel lytic‐phase HLA‐B7‐associated epitope contains essential features required of a component in an EBV peptide‐based vaccine. J. Med. Virol. 72:635–645, 2004. © 2004 Wiley‐Liss, Inc.
Precore/core promoter mutations and genotypes of hepatitis B virus in chronic hepatitis B patients with fulminant or subfulminant hepatitis
Authors: Liu Chun‐Jen , Kao Jia‐Horng , Lai Ming‐Yang , Chen Pei‐Jer , Chen Ding‐Shinn
Published: February 2004

The association of precore stop codon mutation (A1896), dinucleotide mutation (T1762/A1764) in the basic core promoter of hepatitis B virus (HBV) genome, and genotype of HBV with fulminant or subfulminant hepatitis remains controversial. We studied HBV genotypes as well as mutations in the precore and basic core promoter regions in 18 hepatitis B carriers with fulminant or subfulminant hepatitis. Genotyping of HBV was performed by polymerase chain reaction‐restriction fragment length polymorphism. The presence of A1896 in the precore gene and T1762/A1764 in the basic core promoter gene was determined by the polymerase chain reaction and by direct sequencing. Eighteen age‐ and sex‐matched patients with chronic active hepatitis B served as controls. The HBV was of genotype B in 14, genotype C in 3, and unclassified in 1. Precore A1896 mutation occurred in 12 (67%) of the 18 patients. In contrast, the prevalence of basic core promoter mutation was only 17%. Nevertheless, the distribution of HBV genotype and the prevalence of precore A1896 mutation in the fulminant and subfulminant hepatitis patients were similar to those in 18 control patients. In conclusion, the genomic variability of HBV does not seem to contribute to the fulminant and subfulminant exacerbation of chronic hepatitis B in Taiwanese HBV carriers. J. Med. Virol. 72:545–550, 2004. © 2004 Wiley‐Liss, Inc.
Differential binding efficiency between the envelope protein of Japanese encephalitis virus variants and heparan sulfate on the cell surface
Authors: Liu Hsiuan , Chiou Shyan‐Song , Chen Wei‐June
Published: February 2004

Japanese encephalitis (JE) virus infects a number of host cells, either mosquitoes or vertebrates, in nature. The viral envelope (E) protein is known to interact with molecule(s) on the cell membrane during the early stage of virus infection. In this study, two sets of virus variants including T1P1‐L4/T1P1‐S1 and CJN‐L1/CJN‐S1 derived from two strains (T1P1 and CJN) of the JE virus were used to evaluate the effects of genomic variations on virus entry. Each set of virus variant (T1P1‐L4/T1P1‐S1 or CJN‐L1/CJN‐S1) possessed a single amino acid variation in the E protein. The variation of Glu/Lys at E‐306 was found between T1P1‐L4 and T1P1‐S1 whereas the same variation at E‐138 was seen between CJN‐L1 and CJN‐S1. The results showed that heparan sulfate (HS) differentially expressed on the surface of different types of host cells was essential for JE virus infection as shown in an evident difference in attachment efficiency between CHO‐K1 cells and its mutant with defects in GAG biosynthesis. Furthermore, differential interaction of heparin with the envelope protein of JE virus variants implies the significance of virus mutations (especially Lys for E‐138 and/or E306 in this case) that are rather likely involved in determining efficiencies of viral attachment, penetration, and eventual infection. J. Med. Virol. 72:618–624, 2004. © 2004 Wiley‐Liss, Inc.
Identification of rare polymerase variants of hepatitis B virus using a two‐stage PCR with peptide nucleic acid clamping
Authors: Ohishi Waka , Shirakawa Hiroo , Kawakami Yoshiiku , Kimura Sonoko , Kamiyasu Masaya , Tazuma Susumu , Nakanishi Toshio , Chayama Kazuaki
Published: February 2004

Emergence of lamivudine‐resistant variants, with amino acid substitutions in the Tyr‐Met‐Asp‐Asp (YMDD) motif of hepatitis B virus (HBV) reverse transcriptase, is a serious problem in antiviral therapy. Presence of YMDD motif variants in patients who had never been treated with lamivudine has been reported recently. However, no analysis of nucleotide and amino acid sequences of these variants has been performed. In the present study, using polymerase chain reaction (PCR) with peptide nucleic acid (PNA) clamping, we detected many new variants, such as Tyr‐Arg‐Asp‐Asp (YRDD), Tyr‐Met‐Asp‐Asn (YMDN). Many of them had stop codon(s) in overlapping HBs gene. Although the biological activity of these HBV polymerase variants remains to be determined, our results showed that numerous quasispecies are created during virus replication. A typical lamivudine‐resistant Tyr‐Val‐Asp‐Asp (YVDD) variant was detected in only one of 62 (1.6%) anti‐HBe patients with HBV infection before administration of lamivudine. This variant did not have the L528M mutation, which is often associated with YVDD variants, and lamivudine therapy in this patient suppressed HBV replication. Thus, care should be taken when interpreting the results of detection of YMDD variants, especially when the sensitivity of the assay is very high. Amplification of rare variants by PCR with PNA seems a useful tool to examine the emergence of drug‐resistant variants as well as naturally occurring mutants, such as the hepatitis B e antigen (HBeAg) stop codon and vaccine escape mutants. Examination of rare variants should enhance the understanding of the mechanism for emergence of drug‐resistant HBV variants and help in developing strategies for new antiviral drugs. J. Med. Virol. 72:558–565, 2004. © 2004 Wiley‐Liss, Inc.
Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children
Authors: Jartti Tuomas , Lehtinen Pasi , Vuorinen Tytti , Koskenvuo Minna , Ruuskanen Olli
Published: February 2004

The persistence of rhinovirus and enterovirus RNAs was studied in the nasal secretions of children with acute expiratory wheezing (median age: 1.7 years). On admission, 84 samples from 161 (52%) children admitted to hospital were positive by reverse transcriptase‐polymerase chain reaction (RT‐PCR), which detects rhino‐ and enteroviruses simultaneously. Of the samples, 26 (16%) were positive for rhinovirus, 29 (18%) enterovirus and 29 (18%) nontypable rhino‐enterovirus. After 2 weeks, 16 of these 84 (19%) samples were still positive. Rhinovirus RNA remained positive in 13 of 26 (50%) cases, whereas enterovirus RNA remained positive only in 1 of 29 (3%) cases (P = 0.0001). Respiratory symptoms at 2 weeks or systemic glucocorticoid treatment during hospital stay were not related to the persistence of viral RNA. After 5 weeks, only one sample remained PCR‐positive. Thirteen of the 79 (16%) asymptomatic control children were PCR‐positive for respiratory picornavirus. Five of the 13 (38%) PCR‐positive children developed respiratory symptoms in the following week. The study shows that after the onset of symptomatic respiratory infection enterovirus RNA may take 2–3 weeks and rhinovirus RNA 5–6 weeks to disappear from nasal mucus. J. Med. Virol. 72:695–699, 2004. © 2004 Wiley‐Liss, Inc.
Hepatitis in Albanian children: Molecular analysis of hepatitis A virus isolates
Authors: Gabrieli Rosanna , Sanchez Gloria , Macaluso Alessia , Cenko Fabian , Bino Silva , Palombi Leonardo , Buonomo Ersilia , Pinto Rosa M. , Bosch Albert , Divizia Maurizio
Published: February 2004

Hepatitis A is a common disease in developing countries and Albania has a high prevalence of this disease associated to young age. In spite of the occurrence of a unique serotype there are different genotypes classified from I to VII. Genotype characterisation of HAV isolates circulating in Albania has been undertaken, as well as the study of the occurrence of antigenic variants in the proteins VP3 and VP1. To evaluate the genetic variability of the Albanian hepatitis A virus (HAV) isolates, samples were collected from 12 different cities, and the VP1/2A junction amplified and sequenced. These sequences were aligned and a phylogenetic analysis performed. Additionally, the amino half sequence of the protein VP3 and the complete sequence of the VP1 was determined. Anti‐HAV IgM were present in 66.2% of all the sera. Fifty HAV isolates were amplified and the analysis revealed that all the isolates were sub‐genotype IA with only limited mutations. When the deduced amino acid sequences were obtained, the alignment showed only two amino acids substitutions at positions 22 and 34 of the 2A protein. A higher genomic stability of the VP1/2A region, in contrast with what occurs in other parts of the world could be observed, indicating high endemicity of HAV in Albania. In addition, two potential antigenic variants were detected. The first at position 46 of VP3 in seven isolates and the second at position 23 of VP1 in six isolates. J. Med. Virol. 72:533–537, 2004. © 2004 Wiley‐Liss, Inc.
Seroprevalence of human herpesvirus‐8 in blood donors from different geographical regions of Argentina, Brazil, and Chile
Authors: Pérez Celeste , Tous Mónica , Gallego Sandra , Zala Norma , Rabinovich Oscar , Garbiero Susana , Martínez María José , Cunha Andrèa Mendonça Gusmão , Camino Sofía , Cámara Alicia , Costa Sandra Cecília Botelho , Larrondo Milton , Francalancia Verónica , Landreau Fernando , Bartomioli Miguel Angel
Published: February 2004

Human herpesvirus‐8 (HHV‐8) causes Kaposi's sarcoma (KS) and lymphoproliferative disorders in both HIV‐infected and uninfected patients. HHV‐8 has a worldwide occurrence but infection rates vary according to a combination of geographic and behavioral risks. The main transmission route seems to be sexual, nevertheless, nasal secretions, saliva, blood, and organ graft have been proposed. HHV‐8 was postulated as a new infectious agent for screening in blood donors. The aim of this study was to evaluate the prevalence of antibodies against HHV‐8 antigens in blood donors of South America. Serum samples from 2,470 blood donors from Argentina, Brazil, and Chile corresponding to five geographic regions were studied by indirect immunofluorescence assay (IFA). Seroprevalence rate was 3.7% (92/2,470; 95% CI 2.9–4.5) in the entire blood donor population distributed as follows: Argentina, 4.0% (Buenos Aires city, 4.3%; Bahia Blanca, 2.4%; and Córdoba, 4.0%), Campinas (Brazil), 2.8%; and Santiago de Chile, 3.0%. There was no difference (P > 0.05) between men and women or age related, except in Brazil where positive cases were 30–49‐year‐old males. The present study, which includes different geographical areas of multiple countries from South America, has not been done before. The results show similar prevalence rates among the studied zones corresponding to low‐prevalence regions. South America is a large sub‐continent with a wide spectrum of population and geographical characteristics, thus, more HHV‐8 prevalence studies should be necessary to establish possible regional differences. J. Med. Virol. 72:661–667, 2004. © 2004 Wiley‐Liss, Inc.
Decrease of replicative capacity of HIV isolates after genotypic guided change of therapy
Authors: Sarmati L. , Nicastri E. , Montano M. , Dori L. , Buonomini A.R. , d'Ettorre G. , Gatti F. , Parisi S.G. , Vullo V. , Andreoni M.
Published: February 2004

A longitudinal study of the replication capacity of HIV strains isolated from 18 patients failing highly active antiretroviral therapy (HAART) was undertaken at the time of genotypic guided change of therapy and after 12 months. Patients were divided in two groups according to the response to therapy: immune responders (12 patients with immune recovery defined as having more than 100 CD4 cells compared to baseline value), and failing patients (six patients without immune recovery). At enrolment no significant difference in terms of CD4 cell count and HIV plasma viremia was detected between the two groups. One year after change of therapy, all patients experienced a decrease in the replication capacity of HIV strains. The HIV replication capacity of the failing and of immune‐responder patients decreased from 60% (range 14–96%) to 26.4% (range 0.4–74.5) and from 46.8% (range 15–98%) to 3.6% (range 0.1–26.8%), respectively. At month 12, the difference of HIV replication capacity between the two groups reached a statistical significance (P < 0.03). After the change of therapy, an increase in the number of drug resistance mutations in the protease gene was detected in both groups with a higher prevalence of M36I mutation in immune responders. The HIV strains of patients failing HAART showed a progressive impaired replication capacity. The degree of the impairment in viral replication correlated with the viro‐immunological discordant response to HAART and with the acquisition of new drug resistant mutations in the protease gene. In patients failing HAART, the impaired replication capacity of HIV strains could justify the persistence of an immune recovery. J. Med. Virol. 72:511–516, 2004. © 2004 Wiley‐Liss, Inc.
Antibody response to B19 parvovirus VP1 and VP2 linear epitopes in patients with haemophilic arthritis
Authors: Azzi A. , Manaresi E. , Zakrzewska K. , De Santis R. , Musiani M. , Zerbini Marialuisa
Published: February 2004

Parvovirus B19 infection occurs very frequently in patients with haemophilia on account of its transmission with plasma derivatives. In order to achieve a more defined serological pattern for the study of the role of B19 infection in haemophilic arthritis, 53 serum samples from 37 patients with haemophilic arthritis were investigated for the presence of IgG immune response against B19 VP2 and VP1 linear epitopes and VP2 conformational antigen compared to the serological reactivity against B19 NS1 and to the presence of B19 DNA in the synovial membranes. An IgG immune response against VP1 and VP2 linear epitopes was detected by immunoblot assay using recombinant proteins expressed in Escherichia coli. Specific IgG against VP2 and VP1 linear epitopes were present in 84.90 and 92.45% of haemophilic arthritis patients and in 28.0 and 64.0% of the controls (P < 0.001) respectively. All 53 sera of the haemophiliacs (100%) and 66.0% of the controls (P < 0.001) were IgG positive and IgM negative against VP2 structural epitopes. Specific IgG against VP2 linear epitopes, which are a serological marker of active or very recent B19 infection, proved to be significantly associated with the presence of anti‐NS1 antibodies and with the presence of B19 DNA in synovial tissue in patients with haemophilic arthritis. In conclusion, in these patients the presence of B19 IgG anti‐VP2 linear epitopes, in absence of IgM anti‐VP2 structural antigens, can be a useful serological marker to diagnose active, recent or persistent B19 infection. J. Med. Virol. 72:679–682, 2004. © 2004 Wiley‐Liss, Inc.
Risk factors and clinical consequences of human herpesvirus 7 infection in paediatric haematopoietic stem cell transplant recipients
Authors: Chan Paul K.S. , Li C.K. , Chik K.W. , Lee Vincent , Shing Matthew M.K. , Ng K.C. , Cheung Jo L.K. , Fok T.F. , Cheng Augustine F.
Published: February 2004

Human herpesvirus 7 (HHV‐7) is the least studied β‐herpesvirus in transplant settings. This prospective study examined the activity of HHV‐7 during the first 12 weeks post‐stem cell transplant in 59 paediatric patients. The presence of HHV‐7, human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV‐6) in blood was monitored weekly by a multiplex nested polymerase chain reaction. Overall, 33 (55.9%) patients had one or more surveillance blood sample(s) positive for HHV‐7. In contrast to HCMV and HHV‐6, no obvious peak time of reactivation was observed for HHV‐7. The occurrence of HHV‐7 DNAaemia showed a significant negative association with HHV‐6 (P = 0.022), but with no association with HCMV. A significant higher positive rate for HHV‐7 was found in autologous versus allogeneic (P = 0.002), and in peripheral blood versus umbilical cord/marrow (P < 0.001) transplant. Acyclovir had no effect, whereas ganciclovir was associated with a lower rate of HHV‐7 reactivation (P = 0.009). One patient died of HHV‐7 associated brain stem encephalitis. The administration of colony stimulating factor, occurrence of acute graft versus host disease, time to neutrophil and platelet engraftment showed no significant association with the occurrence of HHV‐7 DNAaemia. J. Med. Virol. 72:668–674, 2004. © 2004 Wiley‐Liss, Inc.