bluuebunny/crossref_metadata_2025 huggingface dataset:
Introital ultrasonography: a comparison of women with stress incontinence due to urethral hypermobility and continent women
Authors: Cassadó Jordi , Pessarrodona Antoni , Tulleuda Raquel , Cabero Lluís , Valls Marta , Quintana Salvador , Rodríguez‐Carballeira Mónica
Published: September 2006

OBJECTIVE

To determine if there is a variable on introital ultrasonography (IUS) that can be used to distinguish between women with stress urinary incontinence (SUI) due to urethral hypermobility (UH) and continent women.

PATIENTS AND METHODS

This single‐centre, prospective, blind, cohort, observational study comprised 383 women (245 continent and 138 incontinent) who were all appropriately informed volunteers selected according to the inclusion criteria. IUS with a convex probe was performed on all women; the measurement plane was standardized and coordinates were obtained at rest and on straining. Several distances were measured to determine if any provided an objective distinction between continent and incontinent women.

RESULTS

Among all the IUS variables assessed, sliding (calculated as the difference between the distance urethra‐bladder neck, U‐BN, at rest and under stress) was the best for distinguishing continent and incontinent women. The receiver operating characteristic curves showed that with a threshold of 8 mm, sliding had a sensitivity of 92% and a specificity of 79.6% for detecting SUI due to UH. The distances symphysis‐urethra (S‐U) and U‐BN at rest could also discriminate, but with lower significance.

CONCLUSIONS

IUS is an important tool for diagnosing SUI; there are three independent variables, one dynamic (sliding) and two static (distances S‐U and U‐BN), that can be used to distinguish between continent women and those with SUI due to UH. Sliding is the most reliable, as it has the highest sensitivity and specificity. We think that the simplicity, low financial cost and reliability of IUS could allow it to be a routine procedure for physicians working in incontinence units.
The changing distribution of pT stage in testicular germ cell tumours from 1976 to 2005: a single‐centre analysis of histopathological reports
Authors: Lackner Jakob E. , Koller Anke , Mazal Peter R. , Waldert Mathias , Waldhoer Thomas , Marberger Michael , Kratzik Christian
Published: September 2006

As often happens, the huge interest in prostate cancer is reflected in the many papers which appear in press, and this is the case in this section, with other papers on renal and testicular cancer. However, the papers come from a wide variety of countries from all over the world: Austria, USA, Japan, UK, Italy, Germany and Canada. It is very pleasing to see the international motif of the Journal being maintained.

OBJECTIVE

To assess the changing distribution of stage in seminoma and nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no detailed information on pT stage and vascular invasion, important factors in the decision for further treatment.

PATIENTS AND METHODS

Histopathological reports from 1976 to 2005, from patients who had surgery for testicular tumours at the authors’ institution, were investigated with special focus on pT stage and its distribution. The whole study period was divided into six 5‐year periods. The incidence of seminoma was compared with NSGCT, defined according to the Tumour‐Nodes‐Metastasis (TNM) classification.

RESULTS

In each 5‐year period the median number of tumours treated surgically was 86; the distribution of seminomas and NSGCTs remained stable during the study period (P = 0.201). pT4 and pT3 tumours declined or disappeared in both histopathological groups, while pT2 and pT1 tumours increased during the study period. Since 1996–2000, pT1 tumours decreased, whereas pT2 tumours increased in seminomas (P = 0.085) and NSGCTs (P = 0.003).

CONCLUSION

The incidence of seminoma and NSGCT has not changed over the last 30 years in Vienna. With the establishment of vascular invasion in the TNM classification in 1997, the incidence of pT1 decreased while that of pT2 increased. Since then, the incidence of pT1 tumours in seminomas was 45.8% and 29.1% in NSGCT. According to generally accepted treatment guidelines, these patients might need no adjuvant treatment after surgery.
Comparison of right and left laparoscopic live donor nephrectomy
Authors: Kay Mark D. , Brook Nicholas , Kaushik Monika , Harper Simon J.F. , Bagul Atul , Nicholson Michael L.
Published: September 2006

OBJECTIVE

To compare the anatomy and function of right and left kidneys retrieved by laparoscopic live donor nephrectomy (LDN).

PATIENTS AND METHODS

In all, 84 transperitoneal LDNs were performed, 66 left and 18 right. Two different right‐sided LDN techniques were used: initially, the inferior vena cava (IVC) was controlled with a Satinsky clamp introduced through a 6–8 cm right upper quadrant incision, through which the kidney was also removed (six patients). Subsequently, the IVC was completely mobilized by laparoscopic retrocaval dissection (in 12 patients), allowing the use of a linear stapler‐cutter, including the caval ostium with the renal vein. The kidney was then removed through a short Pfannenstiel incision.

RESULTS

Left kidneys had longer renal veins (38 vs 27 mm; P < 0.05), but there were no differences in arterial length (32 vs 31 mm). Three right kidneys required back‐table renal vein lengthening. The operative duration was shorter for right‐sided LDNs (132 vs 182 min; P < 0.05). The serum creatinine level at 3 months was 131 vs 134 mmol/L for right and left kidneys, respectively.

CONCLUSIONS

Despite faster surgery suggesting that the right LDN is technically easier, there is a greater need for back‐table reconstruction of the renal vein. The functional results of right and left kidneys are equivalent.
Gene expression profiles in mouse urethral development
Authors: Li Jiang , Willingham Emily , Baskin Laurence S.
Published: September 2006

OBJECTIVE

To analyse the gene expression profiles of the mouse genital tubercle (GT) during urethral tube development at embryonic (E) days E14, E15, E16 and E17, as the aetiology of hypospadias, one of the most common congenital anomalies, remains unknown.

MATERIALS AND METHODS

During GT development the urethral folds fuse to form an epithelial seam; subsequently, the epithelial seam disappears, resulting in the normal tubular urethra. Abnormalities in urethral seam formation and remodelling might explain hypospadias, and elucidating the molecular developmental mechanisms underlying normal penile development might provide the basis for understanding hypospadias. Total RNA was isolated from the genital tubercle at embryonic days E14, E15, E16, and E17. Together with reference RNA, sample RNA was labelled with Cy‐3 and Cy‐5 respectively and hybridized to a 16 000‐mouse gene array that included the Incyte GEM2.1 and NIA 7k sets. Candidate genes were analysed by immunohistochemistry and real‐time polymerase chain reaction.

RESULTS

Using cDNA microarrays, we identified the up‐regulation of genes involved in the transforming growth factor (TGF)‐β and Wnt‐Frizzled pathways, and of thrombospondin (TSP) 4, a member of a cell‐migration molecule family, all candidates for involvement in urethral tube formation. Immunohistochemistry showed TGFβ1, TGFβ receptor III, and Frizzled1 were expressed exclusively in E14–E17 urethral epithelium. TSP4 was expressed in the mesenchymal basal layer underlying E17 GT skin epidermis.

CONCLUSIONS

Many signalling pathways are involved in late GT development, and cell migration molecules might have an important role in urethral tube formation.
Do Enhanced Communication Technologies Inhibit or Facilitate Self‐regulated Learning?
Authors: BANYARD PHILIP , UNDERWOOD JEAN , TWINER ALISON
Published: September 2006

The assumption tested here is whether the introduction of enhanced communication technologies in the form of high‐speed broadband connectivity has removed or ameliorated any of the barriers to efficient and effective teaching and learning.i

Evidence is presented of how enhanced communication technologies have facilitated self‐regulated learning. The examples are drawn from a range of subject areas in secondary (11–18 years) and primary (5–11 years) schools in the UK. Evidence is also presented of the new challenges to self‐regulated learning that are created by enhanced communication technologies, for example, non‐selective searching, plagiarism and issues of filtering.

Case studies were developed in 37 schools in the public sector, from rural and urban areas. Field workers conducted interviews with teachers and made classroom observations. Further interviews were also conducted with headteachers and ICT coordinators.

These studies showed some outstanding examples of students taking ownership of the learning process. However, these enhanced communication technologies raised concerns for school management, for teacher workloads and for the parents. These findings are not parochial. International comparisons indicate that we are studying a trans‐national phenomenon. Similarly, costs and benefits of such technologies are not sector specific; the outcomes of this research can inform debate in higher education.
Europe and Flanders: Partners in E‐Learning? A Comparison of Public Policies
Authors: GOEMAN KATIE
Published: September 2006

Working towards e‐learning success in higher education, i.e. the institution‐wide acceptance and use of ICT applications for teaching and learning purposes, means choosing an approach of least resistance. Internal and external consistency or at least complementarity in policy seem crucial. This article presents the results of a desk research concerning the current European and Flemish e‐learning public policy approaches with reference to higher education. By means of a document analysis the author traces policy options and strategies in order to find out if, and to what extent they are attuned. The results show that Flanders has quite successfully converted the European general education and innovation policies to its own policy level. Both are on the same wavelength with regard to political views, strategies and action points. What differs is the pretext in time: Europe advises, Flanders agrees afterwards. Nevertheless, the Flemish policy‐makers need a ‘wake‐up call’ in order to develop an e‐learning action plan with specific measures to enhance e‐learning implementation in the region.
Circadian rhythms in the development of obesity: potential role for the circadian clock within the adipocyte
Authors: Bray M. S. , Young M. E.
Published: September 2006

Obesity is one of the most profound public health problems today, and simplistic explanations based on excessive nutritional consumption or lack of physical activity are inadequate to account for this dramatic and literal growth in our world population. Recent reports have suggested that disruptions in sleep patterns, often linked to our ‘24‐h’ lifestyle, are associated with increased body fat and altered metabolism, although the cause–effect relationship for these associations has yet to be elucidated. Abnormal sleep/wake patterns likely alter intracellular circadian clocks, which are molecular mechanisms that enable the cell/tissue/organism to anticipate diurnal variations in its environment. The environment may include circulating levels of nutrients (e.g. glucose, fatty acids and triglycerides) and various hormones (e.g. insulin, glucocorticoids). As such, alterations in this molecular mechanism, in particular within the adipocyte, likely induce metabolic changes that may potentiate disrupted metabolism, adipose accumulation and/or obesity. Although diurnal variations in adipokines and adipose tissue metabolism have been observed, little is known regarding the molecular mechanisms that influence these events.
Prevalence and socioeconomic risk factors of obesity among urban female students in Al‐Khobar city, Eastern Saudi Arabia, 2003
Authors: Al‐Saeed W. Y. , Al‐Dawood K. M. , Bukhari I. A. , Bahnassy A.
Published: September 2006

The aim of this study was to determine the prevalence and the socioeconomic risk factors associated with obesity among female school‐aged children and adolescents in primary and intermediate schools in Al‐Khobar city, Kingdom of Saudi Arabia. This is a cross‐sectional study conducted in Al‐Khobar city, which is located in the eastern part of Saudi Arabia, during the period of January to March 2003. It involved 2239 female schoolchildren randomly selected from 30 regular government and private primary and preparatory schools. The students’ ages ranged from 6 to 17 years, with a mean of 10.49 ± 2.64 years. A multistage stratified random sampling technique with proportional allocation was used. Data were collected using questionnaires and anthropometric measurements. Body mass index interpretation was based on using a table of standard definitions for overweight and obesity in children (Cole’s). The spss version 10 (SPSS Inc., Chicago, IL, USA) was used for data entry and analysis. A chi‐squared test was used in cross‐tabulation analysis to test the significance of association between body mass index and socioeconomic variables. The prevalence of overweight and obesity were 20% and 11%, respectively. The prevalence of overweight was higher among schoolchildren with father in private work (P < 0.01) and the prevalence of overweight and obesity was higher among schoolchildren with highly educated mothers (P = 0.008). The prevalence of overweight and obesity among female school‐aged children and adolescents in the Al‐Khobar city was very high. Accordingly, it is recommended that health education programmes regarding obesity should be provided to all schoolchildren, their families and teachers.
Prevalence of overweight and obesity among children in the United Arab Emirates
Authors: Malik M. , Bakir A.
Published: September 2006

The aim of the study was to determine the prevalence of overweight and obesity in children in the United Arab Emirates (UAE). Secondary analysis was undertaken of data on 4381 children aged 5–17 years from the 1999 UAE‐National Iodine Deficiency Surveillance Study. Data on weight and height from that study were used to calculate body mass index. The prevalence of overweight and obesity was estimated using International Obesity Task Force criteria. Overall, 944 (21.5%) of children were overweight and 601 (13.7%) of these were obese. More girls than boys were overweight (22.9% vs. 20.2%; P ≤ 0.001). Non‐citizen girls were more likely to be obese (odds ratios [OR] 1.767, 95% confidence intervals [CI] 1.48–2.102) than UAE girls. Boys in the rural areas had the lowest prevalence (23.6%) and were the least likely of all the children to be either overweight (OR 0.785, 95% CI 0.629–0.974) or obese 0.732 (95% CI 0.591–0.912). This study demonstrates a high prevalence of overweight in children in the UAE. Prompt actions are needed to initiate preventative and interventionist strategies to reverse the trend of this emerging epidemic.
The burden of overweight and obesity in the Asia–Pacific region
Authors:   Asia Pacific Cohort Studies Collaboration
Published: September 2006

The rise in the prevalence of overweight and obesity (body mass index ≥25 kg m−2) is, in part, a negative consequence of the increasing economic developments of many lower‐ and middle‐income countries in the Asia–Pacific region. To date, there has been no systematic quantification of the scale of the problem in countries of this region. From the most recent nationally representative estimates for the prevalence of overweight and obesity in 14 countries of the region, it is apparent that overweight and obesity is endemic in much of the region, prevalence ranging from less than 5% in India to 60% in Australia. Moreover, although the prevalence in China is a third of that in Australia, the increase in prevalence in China over the last 20 years was 400% compared with 20% in Australia. In addition, across various countries in the region, the population attributable fractions because of overweight and obesity ranged from 0.8% to 9.2% for coronary heart disease mortality, 0.2% to 2.9% for haemorrhagic stroke mortality, and 0.9% to 10.2% for ischaemic stroke mortality. These results indicate that consequences of overweight and obesity for health and the economy of many of these countries are likely to increase in coming years.
Empowerment in social work: an individual vs. a relational perspective
Authors: Leonardsen Dag
Published: September 2006

Social workers with only an individualistic understanding of empowerment will easily end up as moralising agents rather than as facilitators for their clients. It is in the complex interaction between a given socio‐material situation and the individual capacity to interpret and act that one finds the key to an empowerment worthy of its name. This presupposes two things: that social workers have as a part of their education theoretical knowledge about organisational structures, and that they themselves have been empowered in ways that give them practical competence to act in relation to situations. They need the competence to identify the complexities of interests and power relations in society. The implication of such a recogni‐tion should be clear for the education of social workers:the ideology of empowerment has to be contextualised. To discuss this topic the author makes a distinction between an individua‐listic and a relational perspective and between social problems conceived of as a ‘lack of money’ vs. a ‘lack of meaning’.
Comparative perspectives on changes to Canada's paid parental leave: Implications for class and gender
Authors: Evans Patricia M.
Published: September 2006

In 2001, Canada extended the length of time parents could claim benefits. When combined with maternity benefits, a total of 50 weeks of benefits is available for qualifying parents. This places Canada at the forefront of liberal welfare regimes in benefits for new mothers and parents. However, an examination of the nature and impact of these changes suggests that they further exacerbate gender and class divisions in access to, and take‐up of, these benefits. A discussion of major trends in parental leave policies in Europe identifies the types of changes that are most likely to reduce the gender and class inequalities apparent in current policies.
Culture and social policy: a developing field of study
Authors: van Oorschot Wim
Published: September 2006

This article takes the increased interest in the relation between culture and social policy as a starting point, and discusses how this increasing attention can be understood as the result of contextual factors such as economic, social and academic trends. It discusses these matters and at the same time reviews briefly some of the main findings of studies that contain a cultural perspective in analysing social policy. A second issue concerns the specific character of cultural perspectives in such analyses. Thus far, most studies in the field have been guided by a notion of culture as consisting of the values, norms and beliefs of welfare state actors. Recently, this notion has been questioned by advocates of the so‐called ‘cultural turn’, who suggest that a radical change in the cultural analysis of social policy is required. The article concludes with a discussion of their claims.
Alcohol‐related problems among adolescents and the role of a sense of coherence
Authors: Nilsson Kent W. , Starrin Bengt , Simonsson Bo , Leppert Jerzy
Published: September 2006

Alcohol abuse is generally regarded as a major risk factor for antisocial problem behaviour among adolescents. On the other hand, personal coping strategies hypothetically can be seen as protective of alcohol‐related behaviour problems. The aim of this study was to examine the influence of sense of coherence (SOC) on alcohol‐related behavioural problems in an SOC‐alcohol intoxication model. The method of study was a cross‐sectional, school‐based questionnaire study of 4,305, 16‐ and 19‐year‐old adolescents. We found that both a SOC and the frequency of alcohol intoxication were independently associated with alcohol‐related behavioural problems. Our model shows that the combination of these two independent factors amplifies them considerably, and adolescents with a strong SOC, despite frequent intoxication, were protected to a large degree from experiencing alcohol‐related problems.
Two‐sample Comparison Based on Prediction Error, with Applications to Candidate Gene Association Studies
Authors: Yu K. , Martin R. , Rothman N. , Zheng T. , Lan Q.
Published: September 2006

To take advantage of the increasingly available high‐density SNP maps across the genome, various tests that compare multilocus genotypes or estimated haplotypes between cases and controls have been developed for candidate gene association studies. Here we view this two‐sample testing problem from the perspective of supervised machine learning and propose a new association test. The approach adopts the flexible and easy‐to‐understand classification tree model as the learning machine, and uses the estimated prediction error of the resulting prediction rule as the test statistic. This procedure not only provides an association test but also generates a prediction rule that can be useful in understanding the mechanisms underlying complex disease. Under the set‐up of a haplotype‐based transmission/disequilibrium test (TDT) type of analysis, we find through simulation studies that the proposed procedure has the correct type I error rates and is robust to population stratification. The power of the proposed procedure is sensitive to the chosen prediction error estimator. Among commonly used prediction error estimators, the .632+ estimator results in a test that has the best overall performance. We also find that the test using the .632+ estimator is more powerful than the standard single‐point TDT analysis, the Pearson's goodness‐of‐fit test based on estimated haplotype frequencies, and two haplotype‐based global tests implemented in the genetic analysis package FBAT. To illustrate the application of the proposed method in population‐based association studies, we use the procedure to study the association between non‐Hodgkin lymphoma and the IL10 gene.
Unbiased Interpretation of Haplotypes at Duplicated Microsatellites
Authors: Balaresque P. , Sibert A. , Heyer E. , Crouau‐Roy B.
Published: September 2006

The Y‐chromosome is a powerful tool for population geneticists to study human evolutionary history. Haploid and largely non‐recombining, it should contain a simple record of past mutational events. However, this apparent simplicity is compromised by Y‐linked duplicons, which make up ∼35% of this chromosome; 25% of these duplicons are large inverted repeats (palindromes). For microsatellites lying in these palindromes, two loci cannot be easily distinguished due to PCR co‐amplification, and this order misspecification of alleles generates an additional variance component. Due to this ambiguity, population geneticists have traditionally used an arbitrary method to assign the alleles (shorter allele to locus 1, larger allele to locus 2). Here, we simulate these posterior estimate distributions under three different novel allele assignment priors and compare this with the original method. We use a sample of 33 human populations, typed for duplicated microsatellites lying within palindrome P8, to illustrate our approach. We show that both intra‐ and inter‐population statistics can be dramatically affected by order misspecification. Surprisingly, matrices of pairwise F‐statistics or distance estimates appear far less sensitive to order misspecification and remain relatively unchanged under the priors considered, suggesting that these microsatellites can be considered as useful markers for population genetic studies using an appropriate data treatment. Duplicated microsatellites represent an attractive source of information to investigate the extensive structural polymorphism observed among human Y chromosomes, as well as processes of intra‐chromosomal gene conversion acting between duplicons.
Feeding ecology and seed dispersal of sympatric cheirogaleid lemurs (Microcebus murinus, Cheirogaleus medius, Cheirogaleus major) in the littoral rainforest of south‐east Madagascar
Authors: Lahann P.
Published: September 2006

The lemurs of Madagascar are known for their extraordinary species diversity. The mechanisms that allow the coexistence of these species are still poorly known. Here feeding patterns were investigated for three small nocturnal lemur species of Cheirogaleidae (Microcebus murinus, Cheirogaleus medius and Cheirogaleus major) occurring sympatrically in a littoral rainforest in south‐east Madagascar. During three rainy seasons, the plant species eaten by these three lemurs were described in relation to morphological and biochemical characteristics. All three species were mainly frugivorous and fed on 68 different plant species with small‐ and medium‐sized fruits. A total of 91% of these forage plant species was visited by all three lemur species. Fruits larger than 25–30 mm were avoided. Seeds of a total of 51 food plant species were swallowed and passed the gut unharmed. Thus, even these smaller lemur species play an important role in seed dispersal. There were no differences in the morphological and biochemical characteristics of fruits eaten between the three species, but the feeding height was significantly different between the species. Thus, competition avoidance and niche separation are presumably not based on different feeding patterns of M. murinus, C. medius and C. major in the littoral rainforest, but on different habitat utilization.
Cannibalism and kin recognition inDelena cancerides(Araneae: Sparassidae), a social huntsman spider
Authors: Beavis A. S. , Rowell D. M. , Evans T.
Published: September 2006

Social behaviour in spiders is rare: of the 39 000 species of spiders known, only 23 are considered to be cooperatively social.Delena canceridesis a social species of the huntsman spider that is endemic to Australia. This species is virtually unique among social spiders, having evolved social behaviour in the absence of a snare web. It is thought that this form of social behaviour inD. cancerideshas evolved via the sub‐social route, that is, the extension of an ancestrally occurring period of maternal care and the delayed dispersal of juveniles. Most social spiders show no aggression towards non‐kin conspecifics, prompting suggestions that spiders cannot recognize kin; however,D. canceridesindividuals are highly aggressive towards conspecifics introduced from outside their own colony. In order to determine whether selective aggression inD. cancerideshas its basis in kin recognition, tolerance behaviour was assessed in the context of kinship and size. We observed that, in general, juveniles preferred to starve than engage in cannibalism of any conspecifics, related or not. However, where cannibalism did occur, non‐kin were preferentially eaten, indicating that this species is clearly capable of kin recognition. Size thresholds were also established, below which juveniles are tolerated by adults and above which aggressive interactions leading to death occur. We conclude that kin recognition and juvenile dispersal explain the uncharacteristically high levels of genetic polymorphism in this species.
The evolution of plant–insect mutualisms
Authors: Bronstein Judith L. , Alarcón Ruben , Geber Monica
Published: September 2006

Mutualisms (cooperative interactions between species) have had a central role in the generation and maintenance of life on earth. Insects and plants are involved in diverse forms of mutualism. Here we review evolutionary features of three prominent insect–plant mutualisms: pollination, protection and seed dispersal. We focus on addressing five central phenomena: evolutionary origins and maintenance of mutualism; the evolution of mutualistic traits; the evolution of specialization and generalization; coevolutionary processes; and the existence of cheating. Several features uniting very diverse insect–plant mutualisms are identified and their evolutionary implications are discussed: the involvement of one mobile and one sedentary partner; natural selection on plant rewards; the existence of a continuum from specialization to generalization; and the ubiquity of cheating, particularly on the part of insects. Plant–insect mutualisms have apparently both arisen and been lost repeatedly. Many adaptive hypotheses have been proposed to explain these transitions, and it is unlikely that any one of them dominates across interactions differing so widely in natural history. Evolutionary theory has a potentially important, but as yet largely unfilled, role to play in explaining the origins, maintenance, breakdown and evolution of insect–plant mutualisms.

ContentsSummary412I.Introduction413IIA historical perspective on mutualism413III.Insect pollination414IV.Protection of plants by ants417V.Ant‐mediated seed dispersal419VI.Discussion420Acknowledgements423References424
Breed, gender and neutering status of British dogs with anal sac gland carcinoma
Authors: Polton G. A. , Mowat V. , Lee H. C. , Mckee K. A. , Scase T. J.
Published: September 2006

This study details the breed, gender and neutering status of a large cohort of British canine patients suffering from histologically confirmed anal sac gland carcinoma. Estimates of the relative risk for the development of this disease attributable to these factors are calculated. To reduce the impact of sampling errors, cases were selected from veterinary histopathology laboratories rather than referral hospital databases, and multiple estimates of the general British canine population were used. The weaknesses of the statistical assumptions made are discussed. There was no evidence to support a gender predisposition for the development of this condition. English cocker spaniels are significantly over‐represented, with a mean relative risk estimate of 7.3. The mean relative risk estimate associated with being neutered was 1.4; the effect of neutering appeared to be more significant in male dogs compared with that in female dogs.
Telomerase activity and telomerase reverse transcriptase catalytic subunit expression in canine lymphoma: correlation with Ki67 immunoreactivity
Authors: Renwick M. G. , Argyle D. J. , Long S. , Nixon C. , Gault E. A. , Nasir L.
Published: September 2006

Increased telomerase activity (TA) has been found in human and canine solid tumours, stem cells and somatic tissues with enhanced proliferative potential. The relationship between TA in normal and malignant lymphoid tissues remains unclear. The TA and the expression of canine telomerase reverse transcriptase catalytic subunit (dogTERT) messenger RNA (mRNA) were analyzed in malignant lymph nodes from 30 dogs with lymphoma, from two dogs with non‐neoplastic illness and from two clinically normal dogs, demonstrating a statistically significant difference between TA in lymphoma lymph nodes (n= 30) and normal nodes (n= 4) but no significant difference in dogTERT mRNA expression. In addition, the expression of telomerase reverse transcriptase catalytic subunit (TERT) protein and Ki67 was analyzed in malignant lymph nodes from 10 dogs with lymphoma and from two clinically normal dogs by immunohistochemistry. TERT expression was associated with Ki67 in all lymphoma nodes (n= 10), and differences were illustrated between TERT and Ki67 expression between lymphoma (n= 10) and non‐lymphoma (n= 2) nodes. This data support further investigation of telomerase in canine haematopoietic neoplasia through large‐scale prospective studies.
Quantitative trait loci analysis of mice administered the methionine–choline deficient dietary model of experimental steatohepatitis
Authors: Rangnekar Amol S. , Lammert Frank , Igolnikov Alexander , Green Richard M.
Published: September 2006

Abstract: Background: Nonalcoholic steatohepatitis (NASH) is a common disease with a poorly understood etiology, and the methionine–choline‐deficient (MCD) diet is a nutritional model of NASH. Quantitative trait loci (QTL) analysis is a standard method for chromosomal mapping of polygenic disease traits. The purpose of this study is to administer mice an MCD diet in order to determine the strain‐specific susceptibility for developing steatohepatitis, and to apply a computational methodology of QTL analysis to identify associated chromosomal susceptibility loci.

Methods: Inbred mice were fed an MCD diet and alanine aminotransferase (ALT), hepatic triglycerides, liver weight, and weight loss were measured as phenotypic markers of steatohepatitis.

Results: A/J mice developed the highest ALT and hepatic triglyceride levels. Using linear regression analysis, gene loci affecting serum ALT levels were identified on four chromosomes, and four loci that affect liver weight were also identified. In contrast, no QTLs for hepatic triglycerides or body weight were identified. Of note, loci for ALT and liver weight co‐localized to proximal segments of chromosomes 2 and 15, in regions previously identified as QTLs for liver fibrosis.

Conclusions: These data indicate that experimental steatohepatitis is a polygenic disease with genes determining ALT, liver weight, and liver fibrosis.
Small hepatic nodules (≤2 cm) in cirrhosis patients: characterization with contrast‐enhanced ultrasonography
Authors: Wang Jing‐Houng , Lu Sheng‐Nan , Hung Chao‐Hung , Chen Tai‐Yi , Chen Chien‐Hung , Changchien Chi‐Sin , Lee Chuan‐Mo
Published: September 2006

Abstract: Aim: We evaluated the efficacy of contrast‐enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (≤2 cm) in cirrhosis patients.

Patients and methods: Thirty cirrhosis patients with 30 hepatic nodules (1–2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules.

Results: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study.

Conclusions: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.
Viral factors correlate with hepatitis B e antigen seroconverson in patients with chronic hepatitis B
Authors: Liu Chun‐Jen , Chen Pei‐Jer , Lai Ming‐Yang , Lin Feng‐Yi , Wang Tzusan , Kao Jia‐Horng , Chen Ding‐Shinn
Published: September 2006

Abstract: Background/Aims: Seroconversion (SC) from hepatitis B envelope antigen (HBeAg) to anti‐HBe usually indicates lower viral loads, resolved hepatitis activity and improved long‐term outcomes. However, the role of viral factors in the development of SC remains largely unknown. We thus comprehensively studied these factors in 25 patients with sustained HBeAg SC and seven control patients with sustained loss of HBeAg.

Methods: We determined viral factors in serum samples obtained 1 year before, 6 months before, 3 months before, at the time of, 6 months after and 1 year after HBeAg SC or HBeAg loss. Precore A1896 and basal core promoter T1762/A1764 mutants were determined by polymerase chain reaction (PCR)‐based assays. Serum HBV levels were determined by a real‐time PCR assay.

Results: We found that decline of serum viral load, frequently accompanied by hepatitis exacerbation, occurred within 1 year before HBeAg SC. The proportions of precore and BCP mutations also increased gradually throughout the process of HBeAg SC. The virologic features were similar between HBeAg SC group and HBeAg loss group. Before HBeAg SC or loss, genotype B patients had higher serum viral loads and lower proportions of BCP mutation compared with genotype C patients.

Conclusion: Our findings suggested that viral factors correlate with the development of sustained HBeAg SC or loss.
Apoptosis in liver disease
Authors: Schattenberg Jörn M. , Galle Peter R. , Schuchmann Marcus
Published: September 2006

Abstract: The description of the morphological hallmarks of programmed cell death, apoptosis, in 1972 by Kerr, Wyllie and Currie started a field of research that revolutionized our understanding of cellular proliferation, tissue homeostasis and pathophysiology of many diseases. In the following years, a series of proteins involved in signaling and intracellular death pathways were identified and 30 years later the Noble Prize for physiology and medicine was awarded to S. Brenner, H. R. Horvitz and J. E. Sulston for their discoveries related to describing the mechanisms of cell death (apoptosis). The delineation of the signaling pathways that mediate apoptosis changed the paradigms of understanding in many liver diseases. The most detailed analyzed mode of apoptosis involves a cell surface‐based receptor–ligand system. Death receptors are typically members of the tumor necrosis factor‐receptor superfamily and comprise an intracellular death domain. Following ligand binding to the receptor, intracellular adapter molecules are recruited to the receptor and subsequently transmit the apoptotic signal. Intracellular organelle‐dependent signaling occurs, and effector molecules then augment the receptor‐initiated apoptosis process. Cell death and degradation follows the activation of a highly regulated set of cytosolic and nuclear proteases and DNAses. Receptor‐independent activation of the apoptotic process can occur as part of the cytotoxicity related to UV radiation, chemotherapeuticals or other DNA‐damaging agents through activation of intracellular sensors of cellular integrity, e.g. the tumor suppressor gene p53. In contrast to necrosis, apoptosis is not commonly accompanied by an inflammatory response that causes collateral cell damage. The apoptotic program is highly effective in eliciting cell death and thus must be tightly controlled. This is achieved through continuous integration of pro‐ and antiapoptotic signals at the individual cell level. Dysregulation of the apoptotic process, resulting in too much or too little cell death, has potentially devastating effects and has been implicated in many forms of liver disease like acute liver failure or hepatocellular carcinoma. This review will focus initially on recent progress in signaling events of hepatocellular apoptosis and subsequently discuss the consequences for the hepatic pathophysiology that involves disarrangement of hepatocellular apoptosis.
Role of neutrophils in acute inflammatory liver injury
Authors: Jaeschke Hartmut , Hasegawa Tadashi
Published: September 2006

Abstract: Hepatic infiltration of polymorphonuclear leukocytes (neutrophils) is an early response to tissue injury, cellular stress or systemic inflammation. Neutrophil activation is vital for host‐defense and the removal of cell debris but can also cause additional tissue damage or even liver failure. In order to prevent the detrimental effects of neutrophils without compromising host‐defense reactions, it is important to understand the mechanisms of neutrophil hepatotoxicity. The first step in the pathophysiology is the priming and recruitment of neutrophils into the liver vasculature by inflammatory mediators, e.g. cytokines, chemokines, or complement factors. Most critical for parenchymal cell damage is the accumulation in sinusoids, which does not depend on cellular adhesion molecules. The next step is the extravasation into the parenchyma. This process requires a chemotactic signal from hepatocytes or already extravasated neutrophils and depends on cellular adhesion molecules on neutrophils (β2 or β1 integrins) and on endothelial cells (intercellular or vascular cell adhesion molecules). The third step is the direct contact with target cells (hepatocytes), which involves β2 integrins and triggers the full activation of the neutrophil with a long‐lasting adherence‐dependent oxidant stress and degranulation. The oxidants diffuse into hepatocytes and trigger an intracellular oxidant stress, mitochondrial dysfunction and eventually cause oncotic necrotic cell death. Neutrophil‐derived proteases facilitate extravasation and are involved in the regulation of inflammatory mediator production. Based on these mechanisms, it appears that strengthening of the intracellular defense mechanisms in hepatocytes may be the most promising therapeutic approach to selectively prevent neutrophil‐mediated tissue damage without compromising their host‐defense function.
Comparison of 11C‐acetate positron emission tomography and 67Gallium citrate scintigraphy in patients with hepatocellular carcinoma
Authors: Li Shuren , Beheshti Mohsen , Peck‐Radosavljevic Markus , Oezer Simon , Grumbeck Elke , Schmid Monika , Hamilton Gerhard , Kapiotis Stylianos , Dudczak Robert , Kletter Kurt
Published: September 2006

Abstract: Aims: Nuclear imaging may have an increasing role in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to compare prospectively the Gallium‐67 citrate (67Ga) scintigraphy results with those obtained by positron emission tomography (PET) using 11C‐acetate in patients with HCC.

Methods: We prospectively analysed 21 patients (mean age, 64±11 years) with histopathologically verified HCC undergoing 11C‐acetate PET and 67Ga scintigraphy. 67Ga scans were not performed in three of these 21 patients due to the exacerbation of the disease. Whole‐body 11C‐acetate PET were performed following intravenous injection of 850 MBq of 11C‐acetate. For 67Ga scintigraphy, whole‐body, planar and single photon emission computed tomography imaging acquisitions were performed after intravenous application of a mean dose of 189 MBq 67Ga.

Results: 67Ga scintigraphy found abnormalities only in 10 of 18 patients (56%) and detected 22 of 46 clinically involved sites (48%); it was false‐positive in two patients. 11C‐acetate PET found abnormalities in 14 of 18 patients (78%) and detected 36 of 46 clinical lesions (78%); it was false‐positive in one patients. In one patient with left supraclavicular lymph node metastases, neither the 67Ga scintigraphy nor the conventional computed tomography have shown the lesions, which were clearly demonstrated by the 11C‐acetate PET.

Conclusion: Our results indicate significantly higher sensitivity and specificity of 11C‐acetate PET than 67Ga scan in detection of HCC lesions. This study suggests that imaging with 11C‐acetate PET might play a potential role in the diagnostic workup of patients with HCC.
Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population
Authors: Tanaka Naoki , Tanaka Eiji , Sheena Yo , Komatsu Michiharu , Okiyama Wataru , Misawa Noriko , Muto Hidetomo , Umemura Takeji , Ichijo Tetsuya , Matsumoto Akihiro , Yoshizawa Kaname , Horiuchi Akira , Kiyosawa Kendo
Published: September 2006

Abstract: Background/Aims: As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH.

Methods: First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory examination and US were enrolled. These patients were histologically divided into NASH and non‐NASH groups, and their clinical features were compared. Second, the diagnostic accuracy of predictors of NASH was examined prospectively.

Results: Fifteen patients (28%) were histologically diagnosed as having NASH with mild steatosis. Multivariable analysis revealed that body mass index (BMI) and serum ferritin level were independent predictors of NASH. The best cutoff values to detect NASH were assessed by using receiver‐operating characteristic curves: BMI>25.2 kg/m2 and serum ferritin level >142 ng/ml. When both markers were concomitantly negative, the negative predictive value to detect NASH was 100%.

Conclusions: In cases of mild steatosis, US is not a perfect tool for the accurate diagnosis of NASH. BMI and serum ferritin level are useful discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful markers for diagnosing NASH more accurately in Japanese patients.
Prevalence and Mechanisms of Resistance to Fluoroquinolones in Helicobacter pylori Strains from Patients Living in Belgium
Authors: Bogaerts Pierre , Berhin Catherine , Nizet Henri , Glupczynski Youri
Published: September 2006

Background:  Because of the increasing resistance of Helicobacter pylori against metronidazole and clarithromycin, alternative regimens including newer fluoroquinolones have been developed. We aimed to assess the prevalence as well as the mechanisms of this resistance in clinical isolates originating from patients living in Belgium.

Methods:  Minimal inhibitory concentration (MIC) values of ciprofloxacin, levofloxacin, and moxifloxacin were determined by Etest method on 488 H. pylori isolates originating from patients who underwent upper gastrointestinal endoscopy at 10 different centers. Resistant strains (MIC values > 1 µg/ml) were evaluated for the presence of point mutations in the quinolone resistance‐determining region (QRDR) of the gyrA by amplification and nucleotide sequence.

Results:  Eighty‐two (16.8%) of the strains were found resistant to all fluoroquinolones and 70 of these were further analyzed. Homogeneous and heterogeneous resistance were observed in 55 (78.6%) and in 15 (21.4%) of the strains, respectively. QRDR sequencing revealed various mutations of the codons corresponding to Asn‐87 and Asp‐91 in all isolates with homogeneous resistance. However, in 12 of 15 strains displaying heterogenous resistance, mutations were only detected after subcultures of isolated colonies growing within the ellipse inhibition zone of the E‐test. Amino acid substitutions in the QRDR of GyrA could not be directly related with the MIC values of the isolates. Fluoroquinolone‐resistant mutants were easily selected in vitro at frequencies ranging between 10−6 and 10−7. Such selected mutants stably persisted after several serial passage in antibiotic‐free agar.

Conclusions:  These results suggest that H. pylori resistance to fluoroquinolones is occurring at a high frequency in the Belgian population and that it is essentially mediated through a variety of point mutations occurring in a few loci of GyrA. As a consequence, we strongly suggest to determine the susceptibility of the infecting isolates to fluoroquinolones before administration of an anti‐H. pylori regimen including these agents.