bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent life problems and non‐fatal overdose among heroin users entering treatment
Authors: Neale Joanne , Robertson Michele
Published: January 2005

Aims To investigate the role of recent life problems in non‐fatal overdose among heroin users entering various drug treatment settings.

Design Cross‐sectional data from a longitudinal study investigating drug treatment effectiveness.

Setting Five prison drug treatment services, three residential rehabilitation units, three residential detoxification units and 21 community drug treatment services located in rural, urban and inner‐city areas of Scotland.

Participants Of a total of 793 primary heroin users commencing drug treatment during 2001–02, 337 (42.5%) were prison drug service clients; 91 (11.5%) were residential rehabilitation clients; 97 (12.2%) were residential detoxification clients; and 268 (33.8%) were community drug treatment clients.

Measurements Univariate and stepwise multivariate logistic regression analyses examined associations between overdosing in the 90 days prior to treatment entry and basic demographic characteristics, recent drug use and recent life problems.

Findings Ninety‐one study participants (11.5%) reported at least one overdose and 19 (2.4%) reported more than one overdose in the 90 days prior to treatment entry. A χ2test revealed no significant difference in rates of recent overdosing between the four treatment settings (P = 0.650). Recent drug use and recent life problems—but not demographic characteristics—were associated independently with recent overdosing. However, recent life problems were not associated independently with recent overdosing among clients entering prison, clients entering residential rehabilitation or with multiple recent overdosing.

Conclusions Associations between recent life problems and recent overdose were evident, but varied by treatment setting. Treatment providers should identify and address heroin users’ life problems as part of a broad strategy of overdose prevention.
Response consistency in young adolescents’ drug use self‐reports: a recanting rate analysis
Authors: Percy Andrew , McAlister Siobhan , Higgins Kathryn , McCrystal Patrick , Thornton Maeve
Published: January 2005

Aims  To assess the reliability of drug use reports by young respondents, this study examined the extent of recanting previous drug use reports within an ongoing longitudinal survey of adolescent drug use. Here, recanting was defined as a positive report of life‐time drug use that was subsequently denied 1 year later. The covariates of recanting were also studied.

Design  An ongoing longitudinal survey of young adolescents (Belfast Youth Development Study) in Northern Ireland.

Setting  Pencil and paper questionnaires were administered to pupils within participating schools.

Measurements  Measures analysed included (a) recanting rates across 13 substances, (b) educational characteristics, (c) offending behaviour and (d) socio‐economic status.

Findings  High levels of drug use recanting were identified, ranging from 7% of past alcohol use to 87% of past magic mushroom use. Recanting increased with the social stigma of the substance used. Denying past alcohol use was associated with being male, attending a catholic school, having positive attitudes towards school, having negative education expectations and not reporting any offending behaviour. Recanting alcohol intoxication was associated with being male and not reporting serious offending behaviour. Cannabis recanting was associated with having negative education expectations, receiving drugs education and not reporting serious offending behaviour.

Conclusions  The high levels of recanting uncovered cast doubts on the reliability of drug use reports from young adolescents. Failure to address this response error may lead to biased prevalence estimates, particularly within school surveys and drug education evaluation trials.
Buprenorphine diversion and injection in Melbourne, Australia: an emerging issue?
Authors: Jenkinson Rebecca A. , Clark Nicolas C. , Fry Craig L. , Dobbin Malcolm
Published: January 2005

Aims  To examine indicators of buprenorphine diversion and injection among injecting drug users in Melbourne, Australia and to determine the factors associated with buprenorphine injection.

Design  Melbourne arm of the 2002 Illicit Drug Reporting System (IDRS) cross‐sectional study.

Setting  Five Needle and Syringe Programme sites in Melbourne, Australia.

Participants  A total of 156 current injecting drug users (IDU). Study elibility criteria were at least monthly injection during the previous 6 months, and Melbourne residence for at least the preceding 12 months.

Measurements  Structured questionnaire covering demographic characteristics, drug use history, the price, purity and availability of drugs, criminal activity, risk‐taking behaviours, health‐related issues and general drug use trends.

Findings  Over one‐third (37%) of the study sample reported injecting buprenorphine in their life‐time and 33% reported injecting the drug in the last 6 months. Recent buprenorphine injection was associated with the injection of other drug types (i.e. polydrug injectors), opioid substitution treatment, injection‐related health problems and involvement in crime. Almost half (47%) of those who reported recent buprenorphine injection reported obtaining the drug illicitly at least once during that time.

Conclusions  Given the significant health harms associated with intravenous buprenorphine use (e.g. vein damage, abscesses and infections, precipitated withdrawal, blood‐borne virus transmission, hospitalization and death), routine monitoring of the misuse of buprenorphine in Melbourne is warranted. These results suggest the need for development of effective countermeasures to address diversion and injection of buprenorphine in this setting.
General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial
Authors: De Jong Cor A. J. , Laheij Robert J. F. , Krabbe Paul F. M.
Published: January 2005

Aim  Opioid detoxification by administering opioid‐antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without anaesthesia.

Design  Randomized controlled open clinical trial from September 1999 to August 2001.

Setting  Four addiction centres in collaboration with three general hospitals in the Netherlands.

Participants  A total of 272 opioid‐dependent patients whose previous attempts to abstain were unsuccessful.

Intervention  Patients received rapid detoxification with general anaesthesia (RD‐GA) or without general anaesthesia (RD).

Measurements  Urine screens and an interview (EuropASI) to assess opioid abstinence; two questionnaires (SOOS, OOWS) to measure withdrawal symptoms and one to measure craving (VAS).

Findings  One month after the intervention 62.8% of the patients in the RD‐GA group and 60.0% in the RD group were abstinent for opioids (P = 0.71). No adverse events or complications occurred during RD; however, in the RD‐GA group, five adverse events necessitated admission to a general hospital. The average 1‐month cost for RD was €2517 versus €4439 for RD‐GA.

Conclusions  Rapid detoxification under general anaesthesia did not result in higher levels of opioid abstinence than rapid detoxification without anaesthesia. The cost of the former intervention was much higher.
Decreasing international HIV transmission: the role of expanding access to opioid agonist therapies for injection drug users
Authors: Sullivan Lynn E. , Metzger David S. , Fudala Paul J. , Fiellin David A.
Published: January 2005

Aims  To examine the role of expanded access to opioid agonist treatment as a means to decrease international HIV transmission.

Design  Review of the English language literature via Medline.

Measurements  Estimates of prevalence rates for injection drug use, HIV infection and treatment effect sizes for changes in opioid use, opioid injection, needle‐sharing, injection‐related HIV risk behavior and cost.

Findings  An estimated 12.6 million injection drug users internationally accounted for 10% of the 4.2 million new HIV infections in 2003. Ninety‐three of the 136 countries (68%) that report injection drug use identify HIV infection related to this behavior. Observational studies of methadone treatment demonstrate decreases in opioid use, opioid injection, needle‐sharing and lower rates of HIV prevalence and incidence. The effectiveness of buprenorphine in demonstrating similar findings is expected, although implementations and research are still emerging. The cost‐effectiveness of opioid agonist treatment has been established. The barriers to international adoption of opioid agonist treatment, despite the research evidence and international guidelines, are discussed.

Conclusions  Untreated opioid dependence leads to HIV transmission, on an international level. Opioid agonist treatments are associated with reductions in the frequency of opioid use, fewer injections and injection‐related HIV risk behaviors and lower rates of HIV prevalence and incidence. Despite international recommendations, treatment for opioid‐dependent injection drug users with methadone and buprenorphine is limited. Research, implementation efforts and political strategies to expand access to opioid agonist treatment are needed in order to combat the spread of HIV, especially in the developing world.
CD19 signalling improves the Epstein–Barr virus‐induced immortalization of human B cell
Authors: Hur D. Y. , Lee M. H. , Kim J. W. , Kim J.‐H. , Shin Y. K. , Rho J. K. , Kwack K. B. , Lee W. J. , Han B. G.
Published: January 2005

Abstract.  Epstein–Barr virus (EBV) infection in vitro immortalizes primary B cells and generates B lymphoblastoid cell lines (LCLs). These EBV‐LCLs have been used for several purposes in immunological and genetic studies, but some trials involving these transformations fail for unknown reasons, and several EBV‐LCLs do not grow in normal culture. In this study, we improved the immortalization method by CD19 and B‐cell receptor (BCR) co‐ligation. This method shortens the time required for the immortalization and generation of EBV‐LCLs but does not alter the cell phenotype of the LCLs nor the expression of the EBV genes. In particular, the CD19 and BCR co‐ligation method was found to be the most effective method examined. EBV‐infected B cells induced by CD19 and/or BCR ligation expressed the intracellular latent membrane protein LMP‐1 earlier than EBV‐infected B cells, and the expression of intracellular LMP‐1 was found to be closely related to the time of immortalization. These results suggest that the modified method, using CD19 and/or BCR ligation, may efficiently generate EBV‐LCLs, by expressing intracellular LMP‐1 at an early stage.
Redox‐sensitive transcriptional control by a thiol/disulphide switch in the global regulator, Spx
Authors: Nakano Shunji , Erwin Kyle N. , Ralle Martina , Zuber Peter
Published: January 2005

The Spx protein is indispensable for survival of Bacillus subtilis under disulphide stress. Its interaction with the α‐subunit of RNA polymerase is required for transcriptional induction of genes that function in thiol homeostasis, such as thioredoxin (trxA) and thioredoxin reductase (trxB). The N‐terminal end of Spx contains a Cys–X–X–Cys (CXXC) motif, which is a likely target for redox‐sensitive control. We show here that Spx directly activates trxA and ‐B transcription by interacting with the RNA polymerase α‐subunit, but it does so only under an oxidized condition. The transcriptional activation by Spx requires formation of an intramolecular disulphide bond between two cysteine residues that reside in the CXXC motif. The mechanism of Spx‐dependent transcriptional activation is unique in that it does not involve initial Spx–DNA interaction.
Cell division protein DivIB influences the Spo0J/Soj system of chromosome segregation in Bacillus subtilis
Authors: Real Gonçalo , Autret Sabine , Harry Elizabeth J. , Errington Jeffery , Henriques Adriano O.
Published: January 2005

The initiation of the developmental process of sporulation in the rod‐shaped bacterium Bacillus subtilis involves the activation of the Spo0A response regulator. Spo0A then drives the switch in the site of division septum formation from midcell to a polar position. Activated Spo0A is required for the transcription of key sporulation loci such as spoIIG, which are negatively regulated by the Soj protein. The transcriptional repressing activity of Soj is antagonized by Spo0J, and both proteins belong to the well‐conserved Par family of partitioning proteins. Soj has been shown to jump from nucleoid to nucleoid via the cell pole. The dynamic behaviour of Soj is somehow controlled by Spo0J, which prevents the static association of Soj with the nucleoid, and presumably its transcriptional repression activity. Soj in turn is required for the proper condensation of Spo0J foci around the oriC region. The asymmetric partitioning of the sporangial cell requires DivIB and other proteins involved in vegetative (medial) division. We describe an allele of the cell division gene divIB (divIB80) that reduces the cellular levels of DivIB, and affects nucleoid structure and segregation in growing cells, yet has no major impact on cell division. In divIB80 cells Spo0J foci are not correctly condensed and Soj associates statically with the nucleoid. The divIB80 allele prevents transcription of spoIIG, and arrests sporulation prior to the formation of the asymmetric division septum. The defect in Spo0A‐dependent gene expression, and the Spo– phenotype can be suppressed by expression of divIB in trans or by deletion of the soj‐spo0J locus. However, deletion of the spo0J‐soj region does not restore the normal cellular levels of DivIB. Therefore, the reduced levels of DivIB in the divIB80 mutant are sufficient for efficient cell division, but not to sustain a second, earlier function of DivIB related to the activity of the Spo0J/Soj system of chromosome segregation.
A novel two‐component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes
Authors: Kulasekara Hemantha D. , Ventre Isabelle , Kulasekara Bridget R. , Lazdunski Andrée , Filloux Alain , Lory Stephen
Published: January 2005

Biofilm formation by the opportunistic pathogen Pseudomonas aeruginosa requires the expression of a number of surface adhesive components. The expression of surface organelles facilitating biofilm formation is controlled by environmental signals acting through transcriptional regulatory networks. We analysed the expression of a family of P. aeruginosa adhesins encoded by three distinct fimbrial gene clusters (cupA, cupB and cupC). Using transposon mutagenesis, we have identified several regulatory loci that upregulated cupB and cupC transcription. One such locus contains three components, RocS1, RocR and RocA1, which represent a variant of a classical two‐component signal transduction pathway. RocS1 is a sensor kinase, RocA1 is a DNA binding response regulator that activates cup genes, and RocR is an antagonist of RocA1 activity. Using a two‐hybrid assay, we have shown that RocS1 interacts with receiver domains of both RocA1 and RocR. Expression of the Cup system in response to environmental stimuli is accomplished by a novel mechanism in which the sensor kinase activates its cognate response regulator through a phosphorelay pathway, while an additional repressor protein modulates this interaction.
Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue
Authors: Darwin K. Heran , Lin Gang , Chen Zhiqiang , Li Huilin , Nathan Carl F.
Published: January 2005

A screen for Mycobacterium tuberculosis (Mtb) mutants sensitive to reactive nitrogen intermediates identified transposon insertions in the presumptive proteasomal ATPase gene mpa (mycobacterium proteasome ATPase; Rv2115c). mpa mutants are attenuated in both wild type and nitric oxide synthase 2 deficient mice. In this work, we show that attenuation of mpa mutants is severe, and that Mpa is an ATPase associated with various cellular activities (AAA) ATPase that forms hexameric rings resembling the eukaryotic complex p97/valosin‐containing protein (VCP). Point mutations in the conserved Walker box ATPase motifs of Mpa greatly reduced or abolished ATPase activity in vitro and abrogated protection of Mtb against acidified nitrite. A mutant Mpa protein missing only its last two amino acids retained ATPase activity, yet failed to protect Mtb against nitrite. The corresponding strain was attenuated in mice. Thus, Mpa is an ATPase whose enzymatic activity is necessary but not sufficient to protect against reactive nitrogen intermediates.
Physiological characterization of Saccharomyces cerevisiae kha1 deletion mutants
Authors: Maresova Lydie , Sychrova Hana
Published: January 2005

Maintenance of intracellular K+ homeostasis is one of the crucial requisites for the survival of yeast cells. In Saccharomyces cerevisiae, the high K+ content corresponds to a steady state between simultaneous influx and efflux across the plasma membrane. One of the transporters formerly believed to extrude K+ from the yeast cells (besides Ena1‐4p and Nha1p) was named Kha1p and presumed as a putative plasma membrane K+/H+ antiporter. We prepared kha1 and tok1‐kha1 deletion strains in the B31 and MAB 2d background. Both the strains contain the ena1‐4 and nha1 deletions; that means they lack the main active sodium and potassium efflux systems. MAB 2d has additional trk1 and trk2 deletions, i.e. is impaired in active K+ uptake as well. We performed a large physiological study with these strains to specify the phenotype of kha1 deletion. In our experiments, no difference in K+ content or efflux was observed in strains lacking the KHA1 gene compared with control strains. Two main phenotype manifestations of the kha1 deletion were growth defect on high external pH and hygromycin sensitivity. The correlation between these phenotypes and the kha1 deletion was confirmed by plasmid complementation. Fluorescence microscopy of green fluorescent protein (GFP)‐tagged Kha1p showed that this antiporter is localized preferentially intracellularly (in contrast to the plasma membrane Na+/H+ antiporter Nha1p). Based on these findings, Kha1p is probably not localized in plasma membrane and does not mediate efflux of alkali metal cations from cells, but is important for the regulation of intracelular cation homeostasis and optimal pH control, similarly as the Nhx1p.
Topological insulators inhibit diffusion of transcription‐induced positive supercoils in the chromosome of Escherichia coli
Authors: Moulin Laurent , Rahmouni A. Rachid , Boccard Frédéric
Published: January 2005

The double helical nature of DNA implies that progression of transcription machinery that cannot rotate easily around the DNA axis creates waves of positive supercoils ahead of it and negative supercoils behind it. Using topological reporters that detect local variations in DNA supercoiling, we have characterized the diffusion of transcription‐induced (TI) positive supercoils in plasmids or in the chromosome of wild type Escherichia coli cells. Transcription‐induced positive supercoils were able to diffuse and affect local supercoiling several kilobases away from the site of origin. By testing the effect of various DNA sequences, these reporters enabled us to identify elements that impede supercoil diffusion, i.e. behave as topological insulators. All the elements tested correspond to DNA gyrase catalytic targets. These results correlate the ability of a DNA sequence to be cleaved by DNA gyrase with topological insulator activity. Implications of the asymmetry in supercoil diffusion for the control of DNA topology are discussed.
Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders
Authors: Wanders RJA , Waterham HR
Published: January 2005

The peroxisomal disorders represent a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. The peroxisomal disorders are usually subdivided into two subgroups including (i) the peroxisome biogenesis disorders (PBDs) and (ii) the single peroxisomal (enzyme‐) protein deficiencies. The PBD group is comprised of four different disorders including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum's disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). ZS, NALD, and IRD are clearly distinct from RCDP and are usually referred to as the Zellweger spectrum with ZS being the most severe and NALD and IRD the less severe disorders. Studies in the late 1980s had already shown that the PBD group is genetically heterogeneous with at least 12 distinct genetic groups as concluded from complementation studies. Thanks to the much improved knowledge about peroxisome biogenesis notably in yeasts and the successful extrapolation of this knowledge to humans, the genes responsible for all these complementation groups have been identified making molecular diagnosis of PBD patients feasible now. It is the purpose of this review to describe the current stage of knowledge about the clinical, biochemical, cellular, and molecular aspects of PBDs, and to provide guidelines for the post‐ and prenatal diagnosis of PBDs. Less progress has been made with respect to the pathophysiology and therapy of PBDs. The increasing availability of mouse models for these disorders is a major step forward in this respect.
Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans
Authors: Park H‐J , Lee S‐J , Jin H‐S , Lee JO , Go S‐H , Jang HS , Moon S‐K , Lee S‐C , Chun Y‐M , Lee H‐K , Choi J‐Y , Jung S‐C , Griffith AJ , Koo SK
Published: January 2005

Sensorineural hearing loss associated with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene. In western populations, less than one‐half of the affected individuals with EVA have two mutant SLC26A4 alleles, and EVA is frequently caused by unknown genetic or environmental factors alone or in combination with a single SLC26A4 mutation as part of a complex trait. In this study, we ascertained 26 Korean probands with EVA and performed nucleotide sequence analysis to detect SLC26A4 mutations. All subjects had bilateral EVA, and 20 of 26 were sporadic (simplex) cases. Fourteen different mutations were identified, including nine novel mutations. Five mutations were recurrent and accounted for 80% of all mutant alleles, providing a basis for the design and interpretation of cost‐efficient mutation detection algorithms. Two mutant alleles were identified in 21 (81%), one mutant allele was detected in three (11%), and zero mutant allele was detected in two (8%) of 26 probands. The high proportion of Korean probands with two SLC26A4 mutations may reflect a reduced frequency of other genetic or environmental factors causing EVA in comparison to western populations.
Compound heterozygosity for two non‐synonymous polymorphisms in NPC1L1 in a non‐responder to ezetimibe
Authors: Wang J , Williams CM , Hegele RA
Published: January 2005

Ezetimibe reduces plasma low‐density lipoprotein (LDL) cholesterol by blocking sterol absorption in enterocytes. The NPC1L1 gene product was recently identified as the molecular target for ezetimibe, although functional details are incomplete. We used the non‐response phenotype of plasma LDL cholesterol to ezetimibe treatment to ascertain individuals who might have variant NPC1L1. We found that one non‐responder to ezetimibe was a compound heterozygote for two rare non‐synonymous polymorphisms in NPC1L1 that were absent in normal control subjects. We also characterized other NPC1L1 polymorphisms. While there are many explanations for non‐response to medications, our data suggest a possible relationship between NPC1L1 variation and ezetimibe response and further indicate that a non‐response phenotype might ascertain subjects with genomic DNA variants that could help define metabolic pathways.
Interferon alpha 2b and ribavirin for the treatment of recurrent hepatitis C after liver transplantation: Cohort study of 38 patients
Authors: MUKHERJEE SANDEEP , LYDEN ELIZABETH , MCCASHLAND TIMOTHY M , SCHAFER DANIEL F
Published: January 2005

Aim: Recurrent hepatitis C virus (HCV) is universal following liver transplantation. Patients are often treated with interferon and ribavirin in an attempt to eradicate the virus. We describe our experience with 38 patients with recurrent HCV from a single liver transplant program.

Methods: Between October 2000 and November 2001, 38 patients with recurrent HCV were treated with interferon alpha 2b 3 million units three times a week and ribavirin 1000–1200 mg per day. HCV RNA and liver biopsies were performed before treatment at the end of treatment (EOT), and 6 months after EOT in patients who were HCV RNA negative at EOT.

Results: There were 29 males and nine females. Median age was 49 years. In total, 34 patients were genotype 1 and two each were genotype 3 and 4. Six patients received HCV positive donors and 24 patients (63%) completed treatment. The most common indication for discontinuation of treatment was severe fatigue in 14 patients (37%). On intention to treat analysis, a sustained biochemical and virological response occurred in 10 patients (26%). Unchanged or improved fibrosis scores were present in 37% of patients, of whom 71% were non‐responders to therapy.

Conclusions: Interferon alpha 2b and ribavirin were poorly tolerated in this series of recurrent HCV patients, with sustained HCV eradication occurring in only 26% of patients. However, the majority of non‐responders demonstrated unchanged or improved fibrosis scores, suggesting that a subset of patients may benefit from maintenance antiviral therapy to prevent the development of cirrhosis.
Role of aberrant crypt foci detected using high‐magnification‐chromoscopic colonoscopy in human colorectal carcinogenesis
Authors: HURLSTONE DAVID P , CROSS SIMON S
Published: January 2005

Liaison between gastrointestinal endoscopists and histopathologists is essential to provide the highest standards of diagnostic accuracy and patient management. The histopathologist needs to be aware of the endoscopic findings when interpreting endoscopic biopsies. High‐magnification‐chromoscopic‐colonoscopy (HMCC) is a new technology that provides the endoscopists with much greater resolution and functional staining of the gastrointestinal tract. Using HMCC, the endoscopist is now able to identify subtle changes in the colorectal luminal openings or crypts. Changes in crypt appearances now allow detection of aberrant crypt foci (ACF) in the colon, which might themselves be precancerous lesions but additionally might serve as a valid biomarker of subsequent adenoma and colorectal cancer formation. This article describes the role of the aberrant crypt focus in colorectal carcinogenesis and discusses the clinical impact of HMCC techniques as applicable to ACF.
Prevalence and etiology of persistently elevated alanine aminotransferase levels in healthy Iranian blood donors
Authors: POURSHAMS AKRAM , MALEKZADEH REZA , MONAVVARI AREZOO , AKBARI MOHAMMAD R , MOHAMADKHANI ASHRAF , YARAHMADI SHAHIN , SEDDIGHI NAHID , MOHAMADNEJAD MEHDI , SOTOUDEH MASOUD , MADJLESSI AMIR
Published: January 2005

Background and Aim:  Causes of elevated serum alanine aminotransferase (ALT) levels vary depending on the population under study. The aim of this study was to determine the prevalence and causes of elevated ALT levels among apparently healthy Iranian blood donors in Tehran.

Methods:  A total of 1959 (1465 male) randomly selected blood donors were enrolled in the study. Body mass index (BMI), viral markers and ALT levels were measured. If ALT was elevated (> 40 U/L), it was rechecked twice within 6 months. Blood donors with ≥2 times elevated ALT levels (persistently elevated ALT) were invited for further evaluation.

Results:  A total of 100 donors (5.1%) had elevated ALT levels at the first measurement. Fifty‐two persons (2.65%) were found to have persistently elevated serum ALT. Among subjects with persistently elevated serum ALT, non‐alcoholic steatohepatitis (NASH) was diagnosed in 46 (88.4%), chronic hepatitis C virus (HCV) infection in four (7.7%), alcoholic liver disease in one (1.92%), and drug‐induced liver disease in one (1.92%). The prevalence of NASH and HCV infection in the studied population was 2.35% and 0.4%, respectively. The mean BMI of NASH subjects was 30.58 kg/m2, compared with 27.28 kg/m2 of those without NASH (P < 0.001).

Conclusion:  Non‐alcoholic steatohepatitis is the most common cause of persistently elevated serum ALT in the asymptomatic Iranian blood donors in Tehran.
Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2)
Authors: DUAN XUE‐ZHANG , ZHUANG HUI , WANG MIN , LI HAN‐WEI , LIU JING‐CHAO , WANG FU‐SHENG
Published: January 2005

Background and Aim: To investigate the frequencies, numbers and function of circulating dendritic cell (DC) subsets in patients with hepatitis B virus (HBV) infection, we assayed the circulating precursor DC subsets (including pDC1 and pDC2) and their ability in patients at various stages of HBV infection in vitro.

Methods: Circulating pDC1 and pDC2 frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of DC1, cultured from PBMC in vitro, were detected in patients with chronic hepatitis B (CHB). On behalf of pDC2, interferon (IFN)‐α production of PBMC was determined by the ELISA method in HBV‐infected patients.

Results: The number of circulating pDC1 decreased only in patients with liver cirrhosis (LC) compared with that in normal controls. However, pDC2 numbers decreased in both CHB and LC patients. DC1 from CHB patients showed lower expression of costimulatory molecules CD80, CD86 and impaired allostimulatory mixed lymphocyte reaction (AMLR) compared with those in normal controls. The ability of PBMC to secrete IFN‐α also decreased significantly in patients with chronic HBV infection.

Conclusions: Our results suggest that patients with chronic HBV infection have a significantly lower expression of costimulatory molecules and impaired AMLR of pDC1, as well as decreased number and impaired function of circulating pDC2, which may be partially related to HBV disease progression in these patients.

© 2004 Blackwell Publishing Asia Pty Ltd
Effect of liver cirrhosis on body composition: Evidence of significant depletion even in mild disease
Authors: FIGUEIREDO FÁTIMA APARECIDA FERREIRA , DE MELLO PEREZ RENATA , KONDO MÁRIO
Published: January 2005

Abstract Background and Aims:  Malnutrition is common in liver cirrhosis patients. However, it is under‐diagnosed because liver disease affects the traditional nutritional assessment. An understanding of changes in body composition and the establishment of the tissue‐loss pattern in liver cirrhosis patients could help practitioners to better manage malnutrition in this setting. The aims of this study were: to quantify body composition changes, to determine tissue loss pattern, and to assess the relation of these to the severity of hepatic dysfunction.

Methods:  Seventy‐nine patients and 17 controls were studied. Total body water and extracellular water were measured using dilution techniques. Intracellular water and body cell mass were calculated from these parameters. Total body fat was obtained using absorptiometry.

Results:  Extracellular water was increased and intracellular water was decreased in patients. The two major compartments (body cell mass and body fat) were significantly reduced, mainly in patients with moderate and severe disease. However, significant losses occurred even in Child–Pugh class A patients. We established a tissue‐loss pattern. In Child–Pugh class A patients body fat loss predominated. Child–Pugh class B patients had losses in at least one of the two compartments. Most Child–Pugh class C patients had simultaneous depletion in both compartments.

Conclusions:  Liver cirrhosis was characterized by a significant reduction in body cell mass and body fat and by a redistribution of body water. Significant losses occurred even in patients with mild disease. There was a more pronounced loss of fat in the initial stages, followed by an accelerated loss of body cell mass in the advanced stages of liver cirrhosis.

© 2004 Blackwell Publishing Asia Pty Ltd
Human leukocyte antigen allele associations in type‐1 autoimmune hepatitis patients from western India
Authors: SHANKARKUMAR UMAPATHY , AMARAPURKAR DEEPAK N , KANKONKAR SHARADA
Published: January 2005

Abstract Background and Aims:  The immunogenetic basis of autoimmune diseases has become more and more evident. We have analyzed the human leukocyte antigen (HLA) associations with type‐1 autoimmune hepatitis (AIH) among patients from western India.

Methods:  In 20 patients and 120 healthy controls, polymerase chain reaction amplified with sequence specific primers and hybridized with oligoprobes was carried out to elucidate the HLA A, B, C and DRB1 allele associations.

Results:  The study revealed that A*0222 (20%vs 1.66%; P = 0.0001), A*3201 (15%vs 0.83%; P = 0.0004), A*680102 (30%vs 6.66%; P = 0.001), B*35 (40%vs 11.66%; P = 0.001), B*5501 (10%vs 0.83%; P = 0.008), Cw*0102 (15%vs 1.66%; P = 0.002) and Cw*070101 (50%vs 11.66%; P = 2.5E‐05) were significantly increased among the A, B and C alleles of AIH patients. Among the HLA DRB1 alleles, DRB1*0301 (20%vs 6.19%; P = 0.03), DRB1*1301 (15%vs 2.65%; P = 0.01), DRB1*14 (30%vs 11.5%; P = 0.02) and DRB1*1501 (40%vs 22.12%; P = 0.08) were increased in AIH patients when compared with the controls.

Conclusions:  The present study indicates that the HLA susceptibility to type 1 AIH in the different populations studied is complex.

© 2004 Blackwell Publishing Asia Pty Ltd
Intrahepatic biliary papilloma morphologically similar to biliary cystadenoma
Authors: AOKI SHIGERU , OKAYAMA YASUTAKA , KITAJIMA YASUHIRO , HAYASHI KAZUKI , IMAI HIDETO , OKAMOTO TETSU , AKITA SHINJI , GOTOH KAZUO , OHARA HIROTAKA , NOMURA TOMOYUKI , JOH TAKASHI , YOKOYAMA YOSHIFUMI , ITOH MAKOTO
Published: January 2005

Abstract  A 37‐year‐old man presented complaining of epigastralgia. Abdominal ultrasonography revealed the presence of a papillary tumor (9 mm in diameter) in the cystic lesion (18 mm in diameter) in hepatic segment 4, which was accompanied by mild intrahepatic bile duct dilatation. Although abdominal computed tomography also showed the cystic lesion, it did not show papillary tumors inside the lesion. Endoscopic retrograde cholangiography showed the communication between the cystic lesion and the left hepatic duct. In addition, mucus was observed in the common bile duct. When transpapillary intraductal ultrasonography was performed through the left hepatic duct using a fine ultrasonic probe, a hyperechoic papillary and lobulated tumor was clearly shown in the cystic lesion. The wall of the cyst was smooth and there was no sign of tumor infiltration. Based on these findings, biliary cystadenoma was diagnosed and an extended left lobectomy was carried out. However, pathological findings postoperatively revealed that the lesion was a localized biliary papilloma, developing and extending to the intrahepatic duct. This case is rare and there have been no published reports describing a biliary papilloma morphologically similar to biliary cystadenoma.
Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese
Authors: FAN LIEYING , TU XIAOQING , ZHU YE , ZHOU LIN , PFEIFFER THOMAS , FELTENS RALPH , STOECKER WINFRIED , ZHONG RENQIAN
Published: January 2005

Background: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied.

Methods: Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification.

Results: The result show a significant difference in FokI polymorphism between AIH patients and controls (χ2 = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (χ2 = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differered between Chinese healthy controls and Caucasian healthy controls.

Conclusion: It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver dieseses such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases.

© 2004 Blackwell Publishing Asia Pty Ltd
Impulse control disorders in patients with obsessive–compulsive disorder
Authors: FONTENELLE LEONARDO F. , MENDLOWICZ MAURO V. , VERSIANI MARCIO
Published: January 2005

Abstract  The purpose of the present paper was to identify the rate of prevalence of impulse control disorders (ICD) in patients with obsessive–compulsive disorder (OCD) and to compare patients with OCD with and without ICD with regard to sociodemographic, clinical and prognostic characteristics. Forty‐five patients with OCD were assessed by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn, DSM‐IV) plus additional modules for the assessment of ICD and examined using the Yale–Brown Obsessive–Compulsive Scale, the Clinical Global Impression, the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Global Assessment of Functioning. These patients were treated with serotonin re‐uptake inhibitors (SRI) and followed for a variable period of time. Individuals with ICD (here defined as including not only the impulse control disorders not elsewhere classified of the DSM‐IV, but also other disorders in which impulse control is a prominent feature such as alcohol and drug dependence, paraphilias and bulimia nervosa/binge eating disorder) were compared to those without ICD using the Mann–Whitney U‐test and the Pearson's goodness of fit χ2 test. Sixteen patients with OCD (35.5%) displayed comorbid ICD. Patients with ICD were characterized by a significantly earlier age at OCD onset (P = 0.04), a more insidious appearance of OCD symptoms (P = 0.04), a higher rate of comorbid anxiety disorders (P = 0.03), a greater number (P = 0.02) and severity of compulsive symptoms (P = 0.04), an increased rate of counting compulsions (P = 0.02), and a higher number of required SRI trials (P = 0.01). When OCD is found in association with ICD, the clinical picture is characterized by a greater severity of the obsessive–compulsive symptoms at presentation and by the requirement of a greater number of therapeutic attempts during follow up.
Self‐burning versus self‐cutting: Patterns and implications of self‐mutilation; a preliminary study of differences between self‐cutting and self‐burning in a Japanese juvenile detention center
Authors: MATSUMOTO TOSHIHIKO , YAMAGUCHI AKIKO , CHIBA YASUHIKO , ASAMI TAKESHI , ISEKI EIZO , HIRAYASU YOSHIO
Published: January 2005

Abstract  The purpose of the present paper was to examine the differences in clinical features between self‐cutters and  self‐burners,  to  clarify  clinical  implications  of  self‐mutilating  behaviors  other than self‐cutting. Subjects were 201 delinquent adolescents consecutively entering a Japanese juvenile detention center from February 2003 to March 2003. The subjects were assessed using a self‐reporting questionnaire to evaluate self‐mutilation, traumatic events, and problematic behaviors. Beck Depression Inventory‐2 (BDI‐2) and Adolescent Dissociative Experience Scale (A‐DES) were also tested. Subjects were classified into four groups according to self‐mutilating behaviors: non‐self‐cutting or ‐burning (NSCB), self‐cutting (SC), self‐burning (SB), and self‐cutting and self‐burning (SCB). The questionnaire answers and scores of the BDI‐2 and A‐DES were compared between the four groups. Of 201 subjects, 33 (16.4%) had cut their wrists or forearms at least once, and 72 of 201 (35.8%) had burned themselves at least once. The SC and SCB group had traumatic events, problematic behavior, and various types of self‐mutilating behavior more frequently than the other two groups. The SCB group reported additional types of self‐mutilating behavior more than the SC group. The SCB group also experienced multiple body customizations compared to the SC group, and exhibited higher scores on the BDI‐2 and A‐DES than the other three groups. The self‐burning without self‐cutting may have limited clinical implications. However, the self‐burning with self‐cutting may suggest depression and dissociation, as well as possible indication of self‐mutilating behavior.
Factors related to prescription dosage in Japanese psychiatric hospitals
Authors: NAWATA SHIGEKI , YAMAUCHI KEITA , IKEGAMI NAOKI
Published: January 2005

Abstract  A point prevalence study of prescription dosage was made among psychiatric inpatients in Japan with the following aims: (i) to analyze whether total chlorpromazine equivalent dose was related to patient characteristics or hospital and physician characteristics; and (ii) to analyze whether the usage of the two major categories of antipsychotics, butyrophenone and phenothiazine, were related to their expected pharmacological reactions. A comprehensive database of prescription contents and characteristics of patients, physicians and hospitals was developed from a survey of 1674 patients in 18 psychiatric hospitals. Using the tree‐based model analysis, factors related to the total chlorpromazine equivalent dose were analyzed. Factors included hospital ownership, staffing levels, physician specialty and patient length of stay, symptoms etc. The same analysis was then done for the two major categories of antipsychotics, in order to evaluate whether their expected pharmacological reactions were related to their usage. Factors related to the total chlorpromazine equivalent dose were age of patient, presence of hallucination, age of first psychiatric hospitalization, and change(s) in attending physician (while hospitalized). For the chlorpromazine equivalent dose of the butyrophenone category, the clinical factors related were abnormality in thought and hallucination, and for the phenothiazine category, it was bizarre behavior. Total chlorpromazine equivalent doses had no relationship with hospital or physician characteristics, and appeared to be determined by patient age and psychiatric symptoms. Doses in the butyrophenone category were related to pathological experiences and that in the phenothiazine category to behavioral aspects.
Event‐related potentials in panic disorder and generalized anxiety disorder
Authors: HANATANI TAKASHI , SUMI NORIAKI , TAGUCHI SATOKI , FUJIMOTO OSAMU , NAN‐NO HISASHIGE , TAKEDA MASATOSHI
Published: January 2005

Abstract  To evaluate the neurophysiological differences between panic disorder (PD) and generalized anxiety disorder (GAD), 52 patients with PD and 34 with GAD were investigated using event‐related potentials (ERP). The ERP were recorded using a tone discrimination task, and peak latencies for N1, P2, N2, and P3 at a Pz electrode site were measured. In addition to analyzing the peak latencies of the ERP, the interpeak latencies (IPL; N1–P2, P2–N2, and N2–P3) were also analyzed. The same analysis was performed in 28 age‐matched healthy volunteers (controls). When compared to those of the GAD and control groups, the mean latencies of P2, N2, and P3 were shorter in the PD patients. With regard to the IPL in the PD patients, the N1–P2 IPL was shorter than that in the other groups, and no individual with PD had a longer N1–P2 IPL than 1 SD above the mean of the controls. These findings suggest that certain attention‐related processes in the cerebrum that affect ERP data are accelerated in PD patients. These findings demonstrate that it may be useful to neurophysiologically distinguish PD from GAD by measuring ERP peak latencies and IPL.
Industrial Location and Spatial Inequality: Theory and Evidence from India
Authors: Lall Somik Vinay , Chakravorty Sanjoy
Published: January 2005

The authors argue that spatial inequality of industry location is a primary cause of spatial income inequality in developing nations. Their study focuses on understanding the process of spatial industrial variation: identifying the spatial factors that have cost implications for firms, and the factors that influence the location decisions of new industrial units. The analysis has two parts. First the authors examine the contribution of economic geography factors to the cost structure of firms in eight industry sectors and show that local industrial diversity is the one factor with significant and substantial cost‐reducing effects. They then show that new private sector industrial investments in India are biased toward existing industrial and coastal districts, whereas state industrial investments (in deep decline after structural reforms) are far less biased toward such districts. The authors conclude that structural reforms lead to increased spatial inequality in industrialization, and therefore, income.
Trade Liberalization and Spatial Inequality: a Methodological Innovation in a Vietnamese Perspective
Authors: Jensen Henning Tarp , Tarp Finn
Published: January 2005

The authors calibrate two static computable general‐equilibrium (CGE) models with 16 and 5999 representative households. Aggregated and disaggregated household categories are consistently embedded in a 2000 social accounting matrix (SAM) for Vietnam, mapping on a one‐to‐one basis. Distinct differences in poverty assessments emerge when the impact of trade liberalization is analyzed in the two models. This highlights the importance of modeling micro‐household behavior and related income and expenditure distributions endogenously within a static CGE model framework. The simulations indicate that poverty will rise following a revenue‐neutral lowering of trade taxes. This is interpreted as a worst‐case scenario, which suggests that the government should be proactive in combining trade liberalization measures with a pro‐poor fiscal response to avoid increasing poverty in the short to medium term.