bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic dysfunction in women with bipolar disorder: the potential influence of family history of type 2 diabetes mellitus
Authors: Rasgon Natalie L , Kenna Heather A , Reynolds‐May Margaret F , Stemmle Pascale G , Vemuri Mytilee , Marsh Wendy , Wang Po , Ketter Terence A
Published: August 2010

Rasgon NL, Kenna HA, Reynolds‐May MF, Stemmle PG, Vemuri M, Marsh W, Wang P, Ketter TA. Metabolic dysfunction in women with bipolar disorder: the potential influence of family history of type 2 diabetes mellitus.  Bipolar Disord 2010: 12: 504–513. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  Overweight/obesity, insulin resistance (IR), and other types of metabolic dysfunction are common in patients with bipolar disorder (BD); however, the pathophysiological underpinnings of metabolic dysfunction in BD are not fully understood. Family history of type 2 diabetes mellitus (FamHxDM2), which has been shown to have deleterious effects on metabolic function in the general population, may play a role in the metabolic dysfunction observed in BD.

Methods:  Using multivariate analysis of variance, the effects of BD illness and/or FamHxDM2 were examined relative to metabolic biomarkers in 103 women with BD and 36 healthy, age‐matched control women.

Results:  As a group, women with BD had higher levels of fasting plasma insulin (FPI) and fasting plasma glucose (FPG), higher homeostatic assessment of IR (HOMA‐IR) scores, body mass index (BMI), waist circumference (WC), and hip circumference (HC) compared to control women. FamHxDM2 was associated with significantly worse metabolic biomarkers among women with BD but not among healthy control women. Among women with BD, there was a significant main effect of FamHxDM2 on FPI, HOMA‐IR, BMI, WC, and HC, even after controlling for type of BD illness, duration of medication exposure, and depression severity. Metabolic biomarkers were not influenced by use of weight‐liable psychotropic medication (WLM), even after controlling for type of BD illness, duration of medication exposure, and depression severity.

Conclusions:  Women with BD have overall worse metabolic biomarkers than age‐matched control women. The use of WLM, duration of medication use, type of BD illness, and depression severity did not appear to be associated with more pronounced metabolic dysfunction. FamHxDM2 may represent a risk factor for the development of IR in women with BD. Further, focused studies of the endocrine profiles of families of BD patients are needed.
Performance of the Bipolar Spectrum Diagnostic Scale in psychiatric outpatients
Authors: Zimmerman Mark , Galione Janine N , Chelminski Iwona , Young Diane , Ruggero Camilo J
Published: August 2010

Zimmerman M, Galione JN, Chelminski I, Young D, Ruggero CJ. Performance of the Bipolar Spectrum Diagnostic Scale in psychiatric outpatients. Bipolar Disord 2010: 12: 528–538. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Recent research has suggested that bipolar disorder, when defined to include milder variants such as bipolar II disorder and bipolar disorder not otherwise specified (NOS), is more prevalent than had been previously reported and often underrecognized. Recommendations for improving the detection of bipolar disorder have included careful clinical evaluations inquiring about a history of mania and hypomania and the use of screening questionnaires. The Bipolar Spectrum Diagnostic Scale (BSDS) was designed to be particularly sensitive to the milder variants of bipolar disorder. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the operating characteristics of the BSDS in a large sample of psychiatric outpatients presenting for treatment.

Methods:  A total of 1,100 psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM‐IV and asked to complete the BSDS. Missing data on the BSDS reduced the sample size to 961, approximately 10% (n = 90) of whom were diagnosed with bipolar disorder.

Results:  The sensitivity of the BSDS was similar for bipolar I disorder, bipolar II disorder, and bipolar disorder NOS/cyclothymia. A receiver operating curve (ROC) analysis indicated that cutoffs of 11 and 12 maximized the sum of sensitivity and specificity for the entire group of patients with bipolar disorder (area under curve = 0.80, p < 0.001). The cutoff point associated with 90% sensitivity for the entire sample of patients with bipolar disorder was 8. At this cutoff the specificity of the scale was 51.1% and positive predictive value was 16.0%. We compared the patients with and without bipolar disorder on each of the BSDS symptom items. The odds ratios were higher for the items assessing hypomanic/manic symptoms than items assessing depressive symptoms. We therefore examined the performance of a subscale composed only of the hypomania/mania items. The area under the curve in the ROC analysis was nearly identical to that of the entire scale (0.81, p < 0.001).

Conclusions:  With its high negative predictive value, the BSDS was excellent at ruling out a diagnosis of bipolar disorder; however, the low positive predictive value indicates that it is not good at ruling in the diagnosis. These data raise questions about the use of the BSDS as a screening measure in routine clinical psychiatric practice.
Circadian rhythms and sleep in bipolar disorder
Authors: Murray Greg , Harvey Allison
Published: August 2010

Murray G, Harvey A. Circadian rhythms and sleep in bipolar disorder. Bipolar Disord 2010: 12: 459–472. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  Biological rhythm pathways are highlighted in a number of etiological models of bipolar disorder, and the management of circadian instability appears in consensus treatment guidelines. There are, however, significant conceptual and empirical limitations on our understanding of a hypothesised link between circadian, sleep, and emotion regulation processes in bipolar disorder. The aim of this article is to articulate the limits of scientific knowledge in relation to this hypothesis.

Methods:  A critical evaluation of various literatures was undertaken. The basic science of circadian and sleep processes, their involvement in normal emotion regulation, and the types of evidence suggesting circadian/sleep involvement in bipolar disorder are reviewed.

Results:  Multiple lines of evidence suggest that circadian and sleep‐wake processes are causally involved in bipolar disorder. These processes demonstrably interact with other neurobiological pathways known to be important in bipolar disorder, but are unique in that they are open to behavioural manipulation.

Conclusion:  Further research into biological rhythm pathways to bipolar disorder is warranted. Person‐environment feedback loops are fundamental to circadian adaptation, and models of circadian pathogenesis (and treatment) should recognize this complexity.
Ruling in and ruling out ‘caseness’ in the bipolar spectrum: implications for initial screening
Authors: Goldberg Joseph F
Published: August 2010

Goldberg JF. Ruling in and ruling out ‘caseness’ in the bipolar spectrum: implications for initial screening. Bipolar Disord 2010: 12: 539–540. © 2010 The Author. Journal compilation © 2010 John Wiley & Sons A/S.
The effects of methylene blue on ovine post‐pneumonectomy pulmonary oedema
Authors: SUBOROV E. V. , KUZKOV V. V. , SOBHKHEZ M. , KIROV M. Y. , BJERTNAES L. J.
Published: August 2010

Background: We recently reported that post‐pneumonectomy pulmonary oedema (PPO) occurs after ventilating the remaining lung with excessive tidal volumes. Studies in small animals have indicated that nitric oxide (NO) release increases in hyper‐inflated lungs, but confirmatory evidence from larger animals is still lacking. We hypothesized that PPO could be prevented by methylene blue (MB), an inhibitor of NO synthase.

Methods: Sheep were subjected to a right‐sided pneumonectomy (PE) and randomly assigned to a protectively ventilated group ((PROTV group, n=7) with tidal volumes of 6 ml/kg at 20 inflations/min and a positive end‐expiratory pressure (PEEP) of 2 cmH2O, and two groups undergoing ‘injurious ventilation’ (INJV) with tidal volumes of 12 ml/kg and zero end‐expiratory pressure (ZEEP), a control group (INJV group, n=7) and a treatment group subjected to MB 1 h after PE (INJV+MB group, n=7). Haemodynamic variables, lung mechanics, blood gases and plasma nitrites and nitrates (NOx) were determined.

Results: PE reduced pulmonary blood volume, extravascular lung water (EVLWI) and quasistatic lung compliance in all groups, in parallel with a rise in peak airway pressure (P<0.05). In the INJV group, pulmonary arterial pressure, EVLWI and pulmonary vascular permeability index increased and arterial oxygenation decreased towards cessation of the experiments. These changes were not antagonized by MB. Plasma NOx increased in all the groups compared with baseline, but with no intergroup difference.

Conclusion: MB did not reduce PPO and accumulation of NOx in sheep subjected to ventilation with excessive tidal volumes and ZEEP.
Kinetic analyses of plant water relocation using deuterium as tracer – reduced water flux of Arabidopsis pip2 aquaporin knockout mutants
Authors: Da Ines O. , Graf W. , Franck K. I. , Albert A. , Winkler J. B. , Scherb H. , Stichler W. , Schäffner A. R.
Published: August 2010

Due to reduced evaporation and diffusion of water molecules containing heavier isotopes, leaf water possesses an elevated 18O or 2H steady‐state content. This enrichment has been exploited in plant physiology and ecology to assess transpiration and leaf water relations. In contrast to these studies, in this work the 2H content of the medium of hydroponically grown Arabidopsis thaliana was artificially raised, and the kinetics of 2H increase in the aerial parts recorded during a short phase of 6–8 h, until a new equilibrium at a higher level was reached. A basic version of the enrichment models was modified to establish an equation that could be fitted to measured leaf 2H content during uptake kinetics. The fitting parameters allowed estimation of the relative water flux qleaf into the Arabidopsis rosette. This approach is quasi‐non‐invasive, since plants are not manipulated during the uptake process, and therefore, offers a new tool for integrated analysis of plant water relations. The deuterium tracer method was employed to assess water relocation in Arabidopsis pip2;1 and pip2;2 aquaporin knockout plants. In both cases, qleaf was significantly reduced by about 20%. The organ and cellular expression patterns of both genes imply that changes in root hydraulic conductivity, as previously demonstrated for pip2;2 mutants, and leaf water uptake and distribution contributed in an integrated fashion to this reduced flux in intact plants.
Characterization and mapping of RpsYu25, a novel resistance gene to Phytophthora sojae
Authors: Sun S. , Wu X. L. , Zhao J. M. , Wang Y. C. , Tang Q. H. , Yu D. Y. , Gai J. Y. , Xing H.
Published: August 2010

With 3 figures and 2 tables

Phytophthora root rot (PRR), caused by Phytophthora sojae Kaufm. and Gerd., is one of the most devastating diseases of soybean [Glycine max (L.) Merr.] worldwide. Growing PRR resistant cultivars is the major method of controlling this disease. However, populations of P. sojae, existing in many soybean‐growing regions, cause disease on plants with the known Rps (Resistance to P. sojae) genes. Consequently, the need for new resistance loci is great. Chinese soybean lines ‘Yudou 25’ and ‘Zheng 92116’ showed different reaction types to P. sojae isolates as compared with those with known Rps genes, which suggests that these lines may carry novel resistance loci or alleles. To map the possible gene(s) for PRR resistance in ‘Yudou 25’ and ‘Zheng 92116’, two soybean populations, ‘Yudou 25’ × ‘NG 6255’ and ‘Zheng 92116’ × ‘NH 5’, were evaluated to determine their responses to P. sojae and genotypes of SSR markers. Results indicated that the resistance in these lines was conferred by the same single dominant gene, which is located on MLG N and temporarily designated RpsYu25.
Formation of an Antral Follicle–like Structure of Bovine Cumulus–Oocyte Complexes Embedded Individually or in Groups in Collagen Gels
Authors: Abakushina EV , Morita Y , Kaedei Y , Tanihara F , Namula Z , Viet VL , Otoi T
Published: August 2010

Contents

Culture techniques of antral follicle–like structure (AFLS) derived from cumulus–oocyte complexes (COCs) might provide important insights into follicular development and oocyte maturation. This study was undertaken to investigate the effects of embedding bovine COCs individually (one COC) or in groups (4–5 COCs) in collagen gels on the formation of AFLS and the meiotic status of oocytes. The observations of AFLS formation were performed every second day for 14 days. The AFLS was formed at Day 2 or 4 after the start of culture (Day = 0), irrespective of the culture methods. The mean diameters of AFLS during Days 4–14 using the individual culture method were significantly higher (p < 0.05) than those using the group culture method. However, the AFLS formation rate in the individual culture method was significantly lower compared to that in the group culture method (26.1% vs 62.7%, p < 0.01). Almost all oocytes had undergone the germinal vesicle breakdown stage, irrespective of the culture method or AFLS formation. In conclusion, comparison with the individual culture method revealed that the mean diameters of AFLS in the group culture method were smaller, but more COCs formed AFLS. The group culture method might be useful for evaluating the various hypotheses of follicular formation and interfollicular communication. However, improvement of the group culture system is necessary to prevent the meiotic resumption of oocytes, because the AFLS formation is dependent on the cumulus/granulosa cells surrounding oocytes.
Changes in depression‐related mental health literacy in young men from rural and urban South Australia
Authors: Eckert Kerena A. , Kutek Stephanie M. , Dunn Kirsten I. , Air Tracy M. , Goldney Robert D.
Published: August 2010

Objective:  To examine rural and urban differences in depression‐related mental health literacy, experience of depression and help‐seeking.

Design:  Cross‐sectional population‐based survey stratified by rural and urban area.

Setting:  A random and representative sample of South Australian rural and urban young men aged between 15 and 30 years.

Outcome measures:  Mental health literacy as determined by recognition and exposure to classical symptoms of depression; perceived helpfulness of various interventions and treatment‐seeking behaviour.

Results:  Recognition of depression increased significantly in rural and urban young men between 1998 and 2008. More rural young men than urban men identified symptoms of depression in 1998 (odds ratio (OR): 1.53, 95% confidence interval (CI), 1.01–2.40, P < 0.05), but that was not evident in 2008 (OR: 1.32, 95% CI, 0.80–2.25, P = 0.30). Both groups were more likely to have a close friend experience symptoms of depression and to use antidepressant medications in 2008 compared with 1998. Rural young men experienced a significant increase in recognition of personal depressive symptoms (OR: 3.73, 95% CI, 1.72–8.40) and levels of confidence in psychiatrists and psychologists (OR: 2.40, 95% CI, 1.34–4.31) in 2008 compared with 1998. Both rural and urban young men were significantly less likely to rate dealing with problems on their own as helpful in 2008 as in 1998.

Conclusions:  There has been an increase in both rural and urban young male mental health literacy between 1998 and 2008, especially in rural young men. Whether this will translate into a reduction of depression and associated suicide, with a reversal of the rural/urban suicide differential, remains to be seen.
Evaluating the impact of sustainable comprehensive primary health care on rural health
Authors: Tham Rachel , Humphreys John , Kinsman Leigh , Buykx Penny , Asaid Adel , Tuohey Kathy , Riley Karen
Published: August 2010

Objective:  To develop a conceptual framework for monitoring the relationship between health services and health outcomes in rural Australia.

Design and setting:  Development of an evaluation framework for a rural comprehensive primary health service in Victoria.

Results:  Evidence regarding essential components for successful primary health care, and objective health service and health status measures were combined to develop a conceptual health service evaluation framework. Application of the framework is illustrated using a case study of a rural primary health service in Victoria.

Conclusions:  Inadequate health services limit access to health care, delay use at times of need and result in poor health outcomes. Currently, there is a lack of evidence from rigorous health service evaluations to indicate which rural health services work well, where and why that could inform rural health policies and funding. Although the nature of health service models will vary across communities in order to meet their differing geographic circumstances, there is considerable scope for the translation and generalisation of evidence gained from health service models that are shown to be sustainable, responsive and able to deliver local quality health care. This framework can guide future health service evaluation research and thereby provide a better understanding of a health service's impact on the health of the community and its residents.
Occupational therapists’ self‐insight into their referral prioritisation policies for clients with mental health needs
Authors: Harries Priscilla Ann , Gilhooly Kenneth J.
Published: August 2010

Background/aim:  Obtaining valid accounts of professionals’ thinking is dependent upon experts’ capacity for self‐insight. Self‐insight has implications for developing professional decision making, facilitating education and promoting agreement among therapists. The aim of this study was to examine occupational therapists’ self‐insight into their referral prioritisation policies.

Methods:  A total of 40 occupational therapists individually rated the importance that differing types of referral content had on their prioritisation of referrals. These subjective policies were then correlated with their objective referral prioritisation policies that had been previously statistically derived.

Results:  Self‐insight was found to be moderate but with wide variation across individuals and across referral information used. Self‐insight on cues that were important to the decision was found to be better than on those cues not so important to the decision.

Conclusions:  Occupational therapists have similar levels of self‐insight to other professional groups. The ‘attention hypothesis’ may explain why self‐insight varied across referral information used.
Gastrointestinal stromal tumors: Clinical profile, pathogenesis, treatment strategies and prognosis
Authors: NOWAIN ARASH , BHAKTA HETAL , PAIS SHIREEN , KANEL GARY , VERMA SUMITA
Published: August 2010

Gastrointestinal stromal tumors (GIST), although the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, account for <1% of all GI malignancies. Up to 94% of these tumors express the CD117 antigen. Most patients present in the fifth to seventh decade, the commonest symptom being that of an abdominal mass. Surgery is the main modality of therapy, but even after adequate resection the vast majority of GIST reoccur, and in approximately 50% the liver is the main site of the metastasis. Long‐term, maybe even lifelong follow up of these patients after initial resection cannot be over‐emphasized. Initial tumor size and mitotic rate are the most useful parameters to predict malignant potential. In view of high postoperative recurrence, adjuvant forms of therapy are being explored, and the tyrosine kinase inhibitor imatinib holds the most promise.

© 2005 Blackwell Publishing Asia Pty Ltd
Progressive familial intrahepatic cholestasis: Genetic disorders of biliary transporters
Authors: HARRIS MATTHEW J , LE COUTEUR DAVID G , ARIAS IRWIN M
Published: August 2010

Progressive familial intrahepatic cholestasis types 1, 2 and 3 are childhood diseases of the liver. Benign recurrent intrahepatic cholestasis is predominantly an adult form with similar clinical symptoms that spontaneously resolve. These genetic disorders have significantly helped to unravel the basic mechanisms of the canalicular bile transport processes. Progressive familial intrahepatic cholestasis type 1 involves a gene also linked to benign recurrent intrahepatic cholestasis. The gene codes for an aminophospholipid translocase protein that maintains the integrity of the membrane. How a mutation in this protein causes cholestasis is unknown but is thought to involve the enterohepatic recirculation of bile acids. Progressive familial intrahepatic cholestasis types 2 and 3 involve the canalicular bile salt export pump and a phospholipid translocase, respectively, both of which are fundamental to bile secretion. This review covers the clinical manifestations, genetics, treatment and mechanism of each disease.

© 2005 Blackwell Publishing Asia Pty Ltd
Transcatheter arterial embolization for hemorrhage caused by injury of the hepatic artery
Authors: TZENG WEN‐SHENG , WU RENG‐HONG , CHANG JINN‐MING , LIN CHING‐YIH , KOAY LOK‐BENG , UEN YIH‐HUEI , TIAN YU‐FENG , FONG YAOU
Published: August 2010

Background:  The aims of the study were to compare (i) the effects of transcatheter arterial embolization on initial hemostasis and the control of rebleeding in the treatment of hemorrhage due to hepatic artery injury; and (ii) the outcomes of embolization by different locations.

Methods:  Subjects were 32 patients with suspected hepatic artery injury who were transferred to Chi‐Mei Foundation Medical Center for hepatic angiography and embolization. The causes of arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17). The sites of embolization were classified into four groups: group 1 (n = 8) was classified as ‘combined outlet, target and inlet control’ with embolization of the vascular lesion (target) and hepatic artery distal (outlet) and proximal (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as ‘combined target and inlet control’; group 3 (n = 8) as ‘combined outlet and inlet control’; group 4 (n = 5) as ‘inlet control’ only.

Results:  Successful initial hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both of which were caused by liver injury and occurred in subjects in group 4. Rebleeding was seen in three patients who had successful initial hemostasis: two of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were successfully managed by repeat embolization. Abscess formation was found in two group 1 patients, and both were successfully managed by percutaneous drainage.

Conclusions:  Transcatheter arterial embolization is an effective method for hemostasis in hepatic artery hemorrhage for both patients with liver trauma and patients with iatrogenic injuries to the hepatic artery. Based on this experience, embolization of the vascular lesion and/or the arterial lumen distal to the vascular lesion combined with inlet control is recommended for preventing recurrent hemorrhage, but studies with larger sample sizes will be required to validate this conclusion.
Characteristics of gastritis in patients with Helicobacter pylori‐positive reflux esophagitis
Authors: MIHARA TAKAFUMI , ADACHI KYOICHI , KOMAZAWA YOSHINORI , YOSHIDA MANABU , ARAKI ASUKA , MARUYAMA RIRUKE , FURUTA KENJI , ISHIHARA SHUNJI , AMANO YUJI , KINOSHITA YOSHIKAZU
Published: August 2010

Background and Aim:  The influence of Helicobacter pylori on gastric acid secretion differs with the status of gastritis. The histological characteristics of gastritis in H. pylori‐positive patients with reflux esophagitis have not been fully investigated. We therefore studied the pattern of endoscopic gastric mucosal atrophy and degree of histological gastritis in such patients.

Methods:  Subjects comprised 41 H. pylori‐positive patients with reflux esophagitis, 41 age‐ and sex‐matched patients with duodenal ulcer, and 41 patients with early gastric cancer. The endoscopic pattern of gastric mucosal atrophy was reviewed, and the degree of histological gastritis in biopsy specimens from the antrum and corpus was assessed in accordance with the updated Sydney system.

Results:  The grade of endoscopic and histological gastric mucosal atrophy in patients with reflux esophagitis was significantly lower than that in patients with gastric cancer, and the histological scores for antral atrophy and metaplasia in patients with reflux esophagitis tended to be lower than those in patients with duodenal ulcer. In patients with reflux esophagitis and duodenal ulcer, the scores for antral inflammation and activity tended to be higher than those for the corpus. Conversely, the inflammation and activity score in patients with early gastric cancer showed a corpus‐predominant gastritis pattern.

Conclusion:  In H. pylori‐positive patients with reflux esophagitis, the degree of endoscopic gastric mucosal atrophy is low and histologically there is an antral‐predominant gastritis pattern. Therefore, gastric acid secretion in H. pylori‐positive patients with reflux esophagitis may be augmented by H. pylori infection.
Biliary excretion of taurocholate, organic anions and vinblastine in rats with α‐naphthylisothiocyanate‐induced cholestasis
Authors: KURIHARA HIROKO , SANO NAOYO , TAKIKAWA HAJIME
Published: August 2010

Background and Aims:  α‐Naphthylisothiocyanate (ANIT) is known to cause cholestasis due to injury of the bile duct epithelial cells. The aim of the present study was to examine the effect of a single dose of ANIT on the biliary excretion of various cholephilic compounds and on the amount of canalicular transporters.

Methods:  Twenty‐four hours after the oral administration of ANIT (100 mg/kg), the biliary excretion of taurocholate, leukotriene C4, pravastatin and vinblastine was studied. The protein levels of the bile salt export pump and multidrug resistance protein 2 and the immunostaining of multidrug resistance protein 2 in the liver were also examined.

Results:  The ANIT treatment markedly decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C4, pravastatin and vinblastine. The biliary excretory maximum of taurocholate was also markedly decreased after ANIT treatment. The ANIT treatment had no effect on the protein levels of bile salt export pump and multidrug resistance protein 2 and the immunostaining of multidrug resistance protein 2 in the liver.

Conclusions:  These findings support canalicular transporters having little effect on the marked impairment of biliary excretion of cholephilic compounds in ANIT‐induced cholestasis.

© 2005 Blackwell Publishing Asia Pty Ltd
Gender differences in vascular reactivity of aortas from rats with and without portal hypertension
Authors: ROBERT RENÉ , CHAGNEAU‐DERRODE CARINE , CARRETIER MICHEL , MAUCO GÉRARD , SILVAIN CHRISTINE
Published: August 2010

Background: Inflammatory responses related to portal hypertension may be different in male and female rats. Most experimental studies of portal hypertension have involved male animals, and little information is available on gender differences in this setting. The aim of the present study was to compare aortic reactivity in female and male rats with and without portal hypertension.

Methods: Contraction response curves to phenylephrine were studied with aortic rings, with and without endothelium. For relaxation studies, rings were precontracted with phenylephrine 10−7 mol/L and then exposed to acetylcholine 10−4 mol/L. Portal hypertension was provoked by calibrated portal stenosis performed 2 weeks before experiments.

Results: In non‐hypertensive conditions, the contractile response to increasing phenylephrine concentrations was significantly stronger in rings from male than female rats, both with and without endothelium. In male rats with portal hypertension, the phenylephrine concentration–response curves were lowered and shifted to the right in aortic rings both with and without endothelium. In female rats, portal hypertension did not induce significant changes in the phenylephrine concentration–response curves. In female rats, portal hypertension induced a marked increase in relaxation (157 ± 123% vs 81 ± 64% in controls); the increase was also stronger than that in male rats with portal hypertension (95 ± 6%;P < 0.01).

Conclusion: Clear gender differences were observed in vasoconstrictor responsiveness of aortic rings from rats with and without portal hypertension. Contrary that in male rats, portal hypertension did not induce vascular hyporesponsiveness in female rats. Further investigations are required to explain these differences
Histone deacetylase inhibitors, anticancerous mechanism and therapy for gastrointestinal cancers
Authors: FANG JING YUAN
Published: August 2010

Abstract  Histone acetylation regulates gene transcription. Histone acetylation is a reversible process: histone acetyltransferases (HAT) transfer the acetyl moiety from acetyl coenzyme A to the lysine, and histone deacetylases (HDAC) remove the acetyl groups re‐establishing the positive charge in the histones. HDAC inhibitors have antiproliferative activity against human cancer cells via cell cycle arrest, pro‐differentiation, and pro‐apoptosis. In recent years, many studies have shown that specific HDAC inhibitors are helpful for gastrointestinal cancer therapy.
Quality of life measures for fecal incontinence and their use in children
Authors: TRAJANOVSKA MISEL , CATTO‐SMITH ANTHONY G
Published: August 2010

Background:  Fecal incontinence is a common problem within society from childhood through to the elderly. Its clinical assessment has focussed on severity and frequency of soiling episodes but it is increasingly recognized to have an impact on physical, psychological and social well‐being (quality of life [QOL]). This is likely to be particularly important in childhood. The aim of the present study was to critically evaluate the development and application of disease‐specific QOL measures, focusing particularly on their use in children.

Methods:  Generally recognized disease‐specific QOL measures for fecal incontinence were identified and their generation and validation were critically evaluated.

Results:  Six instruments were identified: Ditesheim and Templeton QOL Scoring System, Manchester Health Questionnaire, Hirschsprung's Disease/Anorectal Malformation Quality of Life Questionnaire (HAQL), Gastrointestinal Quality of Life Index (GIQLI), Fecal Incontinence TyPE Specification, and the Fecal Incontinence Quality of Life Scale (FIQL). Although the FIQL appeared to be the better tool for adults with fecal incontinence because it was brief and had the best validity and reliability, it needed further modification to become appropriate for use in children. In particular, items relating to sexual activity were inappropriate.

Conclusion:  Neither the FIQL nor other disease‐specific instruments met basic psychometric standards for use in children with fecal incontinence. Substantial revision of currently available instruments will be required to meet the needs of this population.
Comprehensive clinical assessment improves the accuracy of predicting cirrhosis in chronic hepatitis C
Authors: GORDON ADAM , BAILEY MICHAEL J , GIBSON PETER R , ROBERTS STUART K
Published: August 2010

Background:  The diagnosis of cirrhosis in chronic hepatitis C (CHC) is important but difficult in those who are unable to undergo liver biopsy. Thus, the aims of the present study were to compare separately and in combination, clinical markers of liver disease, the discriminant score (DS) and serum hyaluronic acid (HA) for their ability to predict cirrhosis in CHC.

Methods:  Two groups of consecutive patients (groups 1 and 2) with CHC were analyzed. Clinical data and routine laboratory results at the time of liver biopsy were collected, and serum HA levels were assayed. A clinical examination score (CES) was constructed using the sum of clinical markers of liver disease in group 1 and was validated in group 2, the DS was calculated, and a serum HA score (HAS) was produced. Combination scores were constructed using the sum of the CES, DS and HAS. Histological analysis of liver biopsies was performed by hepatopathologists blinded to clinical results.

Results:  One hundred and fifty‐one patients with CHC (group 1, n = 47; group 2, n = 104) including 27 with cirrhosis were assessed. Serum HA was more accurate than either CES or DS in the prediction of cirrhosis. The combination of CES, DS and HAS enabled the most accurate prediction of cirrhosis with a sensitivity and specificity of 78% and 93%, and a positive predictive value and negative predictive value of 75% and 94%, respectively.

Conclusions:  A comprehensive clinical assessment utilizing clinical and laboratory data more accurately predicts the presence and absence of cirrhosis in CHC than individual markers.
Prehepatic portal hypertension produces increased mast cell density in the small bowel and in mesenteric lymph nodes in the rat
Authors: PRIETO ISABEL , ALLER MARÍA‐ANGELES , SANTAMARÍA LUIS , NAVA MARÍA‐PAZ , MADERO ROSARIO , PÉREZ‐ROBLEDO JUAN‐PEDRO , ARIAS JAIME
Published: August 2010

Background:  Because most of the characteristics of the portal hypertensive enteropathy can be explained on the basis of increased levels of mast cell mediators, the purpose of the present paper was to study mast cell splanchnic infiltration.

Methods:  Duodenum, jejunum, ileum and mesenteric lymph node complex infiltration by mast cells was assayed by a stereological technique in control rats (group I; n = 5) and in an experimental model of portal hypertension (the portal vein‐stenosed rat, group II; n = 5) at 6 weeks after operation.

Results:  Intestinal and mesenteric lymph node complex infiltration by mast cells increased in the animals with partial portal vein ligation. The mast cell density progressively increased distally along the small bowel. The mast cell increase in the mesenteric lymph node complex in portal vein‐stenosed rats was greater than in the duodenum (P = 0.001), jejunum (P = 0.006) and ileum.

Conclusion:  The rise of mast cells density in the small bowel and mesenteric lymph node complex in rats with partial portal vein ligation suggests that these cells are involved in the etiopathogenesis of experimental portal prehepatic hypertensive enteropathy.
Expression of Ep‐CAM in intestinal metaplasia, gastric epithelial dysplasia and gastric adenocarcinoma
Authors: JOO MEE , KIM HANSEONG , KIM MIN KYUNG , YU HANG JONG , KIM JIN‐POK
Published: August 2010

Background:  The epithelial cell adhesion molecule (Ep‐CAM) is widely associated with human carcinomas. However, the expression and distribution of Ep‐CAM in gastric premalignant and malignant lesions are not well known.

Method:  We examined the expression of Ep‐CAM in 99 cases of gastric adenocarcinoma and associated uninvolved gastric mucosa, 39 cases of gastric biopsy specimens with chronic gastritis (CG) with or without intestinal metaplasia (IM) (25 cases) and gastric epithelial dysplasia (GED) (14 cases) by immunohistochemical staining. In gastric adenocarcinoma, we correlated the results with established prognostic factors, and in IM and GED, with Hepatocyte paraffin 1 (Hep Par 1) expression, introduced as a marker of IM.

Results:  Ep‐CAM overexpression was noted in 0% of normal epithelia, 93.9% of IM, 42.9% of GED and 34.3% of adenocarcinoma. The average immunostaining score of normal epithelia, IM, GED and gastric adenocarcinoma was 0.14 (± 0.26), 7.18 (± 1.93), 5.67 (± 2.29) and 4.09 (± 1.89), respectively. There were significant differences among the groups. Ep‐CAM overexpression in adenocarcinoma correlated with Lauren classification and histologic grade, but not with tumor stage, lymph node metastasis and p53 expression. Both Ep‐CAM and Hep Par 1 expressions showed excellent correlations with IM (P < 0.0001). Ep‐CAM expression was consistently observed in all cases of GED with a moderate to strong intensity, and Hep Par 1 weakly in 10 out of 14 cases.

Conclusion:  Our findings suggest that increased levels of Ep‐CAM represent an early event in gastric carcinogenesis, and seem to have a specific relation with the development of IM as a morphoregulatory molecule.
Factors influencing stem cell differentiation into the hepatic lineage in vitro
Authors: HENG BOON CHIN , YU HANRY , YIN YIJUN , LIM SENG GEE , CAO TONG
Published: August 2010

Abstract  A major area of research in transplantation medicine is the potential application of stem cells in liver regeneration. This would require well‐defined and efficient protocols for directing the differentiation of stem cells into the hepatic lineage, followed by their selective purification and proliferation in vitro. The development of such protocols would reduce the likelihood of spontaneous differentiation of stem cells into divergent lineages upon transplantation, as well as reduce the risk of teratoma formation in the case of embryonic stem cells. Additionally, such protocols could provide useful in vitro models for studying hepatogenesis and liver metabolism. The development of pharmokinetic and cytotoxicity/genotoxicity screening tests for newly developed biomaterials and drugs, could also utilize protocols developed for the hepatic differentiation of stem cells. Hence, this review critically examines the various strategies that could be employed to direct the differentiation of stem cells into the hepatic lineage in vitro.
Association of functional gene polymorphisms of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐9 with the progression of chronic liver disease
Authors: OKAMOTO KINYA , MIMURA KENICHI , MURAWAKI YOSHIKAZU , YUASA ISAO
Published: August 2010

Background and Aims:  Matrix metalloproteinases (MMP) play an important role in the progression of liver fibrosis in addition to fibrogenesis. MMP‐1, MMP‐3, and MMP‐9 gene polymorphisms have been shown to influence the transcriptional activity of their respective gene promoter in an allele‐specific manner. The aim of this study was to examine the possible association of MMP‐1, MMP‐3, and MMP‐9 gene polymorphisms with the progression of chronic liver disease in the Japanese population.

Methods:  We examined 91 patients with HCV‐related chronic hepatitis and 89 patients with HCV‐related liver cirrhosis. We determined MMP‐1 1G/2G, MMP‐3 5A/6A, and MMP‐9 C/T polymorphisms using polymerase‐chain reaction based assays.

Results:  In MMP‐1 genotypes, the 2G homozygotes were significantly more in cirrhotic group than in chronic hepatitis group. In MMP‐3 genotypes, there were no significant differences in genotype distributions and allele frequencies between chronic hepatitis and liver cirrhosis groups. However, 5A carriers had a significantly lower age at liver cirrhosis diagnosis and a higher Child–Pugh score compared with the 6A homozygotes. In MMP‐9 genotypes, the C homozygotes and C allele frequencies were significantly more in liver cirrhosis group than in chronic hepatitis group.

Conclusion:  These findings suggest that MMP‐1, MMP‐3, and MMP‐9 gene polymorphisms account for some of the variability in the progression of HCV‐related chronic liver diseases.
Neutral lipid isolated from endosperm of Job's tears inhibits the growth of pancreatic cancer cells via apoptosis, G2/M arrest, and regulation of gene expression
Authors: BAO YING , YUAN YAOZONG , XIA LU , JIANG HUA , WU WEIRONG , ZHANG XUEJUN
Published: August 2010

Background:  The neutral lipid isolated from the endosperm of Job's tears (NLEJ) has been known to possess an anticancer activity with relatively low toxicity. The present study was designed to examine its antiproliferative effects in the PaTu‐8988 and SW1990 human pancreatic cancer cells and to investigate its potential mechanism(s).

Methods:  Pancreatic cancer cells were treated with NLEJ to evaluate cell viability, cell cycle progression, nuclear morphology, DNA fragmentation and annexin V binding analysis. Regulation of gene expression was determined by using cDNA microarrays and western immunoblotting.

Results:  The NLEJ induced a dose‐ and time‐dependent inhibition of proliferation in both PaTu‐8988 and SW1990 cell lines. Further studies were carried out with only the PaTu‐8988 cells. Flow cytometry analysis showed that NLEJ blocked cell cycle progression at the G2/M phase. There was also an increase in annexin V binding and DNA fragmentation, indicative of apoptosis. The cDNA microarray analysis with cell cycle‐ and apoptosis‐targeted arrays showed that the expression signals of 24 genes were found to be significantly altered at 24 h of NLEJ treatment. These genes are involved in cell cycle control (e.g. p21, p27, CDK2, and cyclins), apoptosis regulation (e.g. bcl‐2 and bax), and signal transduction (e.g. ATM, RAD50, and p53). Some of these results were confirmed by western blot analysis.

Conclusions:  These data show that NLEJ inhibits pancreatic cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Therefore, NLEJ might be a chemotherapeutic agent against pancreatic cancer.

© 2005 Blackwell Publishing Asia Pty Ltd
Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa
Authors: KODAMA MASAAKI , FUJIOKA TOSHIO , MURAKAMI KAZUNARI , OKIMOTO TADAYOSHI , SATO RYUGO , WATANABE KOICHIRO , NASU MASARU
Published: August 2010

Background:  Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication.

Methods:  Biopsy specimens were obtained from 31 patients with H. pylori‐infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non‐infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2.

Results:  Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3‐fold; P < 0.01), and in the gastric antrum (2.0‐fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7‐fold; P < 0.01), and in the antrum (3.5‐fold; P < 0.01). In the non‐infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori‐infected group.

Conclusion:  A significant increase is shown in p53 and MDM2 expression in H. pylori‐infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.
Low‐dose rabeprazole, amoxicillin and metronidazole triple therapy for the treatment of Helicobacter pylori infection in Chinese patients
Authors: WONG WAI MAN , HUANG JIAQING , XIA HARRY HX , FUNG FIONA MY , TONG TERESA SM , CHEUNG KESS L , HO VICKY YK , LAI KAM CHUEN , CHAN CHI KUEN , CHAN ANNIE OO , HUI CHEE‐KIN , LAM SHIU KUM , WONG BENJAMIN CY
Published: August 2010

Background:  Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to  be  an  effective  second‐line  treatment  of Helicobacter  pylori  infection.  The  effects  were  compared of 7‐day low‐dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients.

Methods:  Helicobacter pylori‐positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM‐10) or (ii) high‐dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM‐20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by 13C‐urea breath test 5 weeks after stopping medications. Side‐effects of treatments were documented.

Results:  A total of 120 patients were eligible for analysis. By intention‐to‐treat and per‐protocol analysis, the eradication rates were 83% and 86% in the RAM‐10 group and 75% and 76% in the RAM‐20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well‐tolerated and compliance was >98% in both groups.

Conclusions:  Low‐dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well‐tolerated therapy for the treatment of H. pylori infection in Chinese population.
Pancreatic carcinoma that completely obstructs the Wirsung duct without dilatation of the main pancreatic duct
Authors: Sugiyama Masanori , Izumisato Yumi , Abe Nobutsugu , Masaki Tadahiko , Mori Toshiyuki , Atomi Yutaka
Published: August 2010

Background and Aim:  Pancreatic carcinomas in which the main pancreatic duct (MPD) is completely obstructed are almost always associated with dilatation of the upstream MPD. However, some carcinomas are not associated with MPD dilatation despite complete MPD obstruction. This paradoxical phenomenon has not been well documented.

Methods:  The findings from endoscopic retrograde cholangiopancreatography in 207 cases of pancreatic head carcinomas were analyzed with special reference to this unique type of carcinoma. Twenty‐five of the patients were found to exhibit no MPD dilatation on ultrasonography, computed tomography or magnetic resonance imaging.

Results:  Pancreatography via the major papilla showed complete obstruction of the MPD (112 patients with MPD dilatation and 6 without), stenosis (70 and 10, respectively), or no abnormal findings (0 and 9, respectively). In all six patients with complete MPD obstruction but without upstream MPD dilatation, injection of the minor papilla revealed a non‐dilated dorsal pancreatic duct. The size of the obstructive carcinomas with and without MPD dilatation was comparable.

Conclusions:  Some (3%) pancreatic head carcinomas are not associated with MPD dilatation despite complete obstruction of the Wirsung duct. In such cases, the Santorini duct drains the dorsal pancreatic duct, completely compensating for the obstructed Wirsung duct. Attention should be paid to this unique type of carcinoma in diagnosing pancreatic head carcinomas.