bluuebunny/crossref_metadata_2025 huggingface dataset:
Apigenin induces apoptosis via downregulation of S‐phase kinase‐associated protein 2‐mediated induction of p27Kip1 in primary effusion lymphoma cells
Authors: Hussain A. R. , Khan A. S. , Ahmed S. O. , Ahmed M. , Platanias L. C. , Al‐Kuraya K. S. , Uddin S.
Published: January 2010

Objective:  The mechanisms that regulate mitogenic and antiapoptotic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we assessed the effect of apigenin (4′,5,7‐trihydroxyflavone), a flavonoid on a panel of PEL cell lines.

Materials and methods:  We studied the effect of apigenin on four PEL cell lines. Apoptosis was measured by annexin V/PI dual staining and DNA laddering. Protein expression was measured by immunoblotting.

Results:  Apigenin induced apoptosis in PEL cell lines in a dose dependent manner. Such effects of apigenin appeared to result from suppression of constitutively active kinase AKT resulting in down‐regulation of SKP2, hypo‐phosphorylation of Rb and accumulation of p27Kip1. Apigenin treatment of PEL cells caused dephosphorylation of p‐Bad protein leading to down regulation of the anti‐apoptotic protein, Bcl‐2 and an increase in Bax/Bcl2 ratio. Apigenin treatment also triggered Bax conformational change and subsequently translocation from cytosole to mitochondria causing loss of mitochondrial membrane potential with subsequent release of cytochrome c. Released cytochrome c onto the cytosole activated caspase‐9 and caspase‐3, followed by polyadenosin‐5′‐diphosphate‐ribose polymerase (PARP) cleavage. Finally, treatment of PEL cells with apigenin down‐regulated the expression of inhibitor of apoptosis protein (IAPs).

Conclusions:  Altogether, these data suggest a novel function for apigenin, acting as a suppressor of AKT/PKB pathway in PEL cells, and raise the possibility that this agent may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.
ADHD and academic performance: why does ADHD impact on academic performance and what can be done to support ADHD children in the classroom?
Authors: Daley D. , Birchwood J.
Published: January 2010

This paper reviews the relationship between attention deficit hyperactivity disorder (ADHD) and academic performance. First, the relationship at different developmental stages is examined, focusing on pre‐schoolers, children, adolescents and adults. Second, the review examines the factors underpinning the relationship between ADHD and academic underperformance: the literature suggests that it is the symptoms of ADHD and underlying cognitive deficits not co‐morbid conduct problems that are at the root of academic impairment. The review concludes with an overview of the literature examining strategies that are directed towards remediating the academic impairment of individuals with ADHD.
Effect of applying a treatment threshold in a population. An example of pulmonary tuberculosis in Rwanda
Authors: Van den Ende Jef , Mugabekazi Julie , Moreira Juan , Seryange Eric , Basinga Paulin , Bisoffi Zeno , Menten Joris , Boelaert Marleen
Published: January 2010

Purpose  Clinicians often think treatment thresholds should be adapted to the setting. We intended to explore the effect in terms of harm because of false negatives and true and false positives of the application of a treatment threshold for pulmonary tuberculosis from a patient's perspective at different prevalence levels in a developing country.

Methods  In a cohort of 300 patients with chronic cough, we estimated the prevalence of pulmonary tuberculosis, and the sensitivity and specificity of key predictors with latent class analysis (LCA). We computed the post‐test probability of individual patients based on these data. With disease‐ and treatment‐related mortality and morbidity, and without cost or regret, we calculated the break‐even point of disease probability where treating versus not treating resulted in similar total harm from the patient's perspective. We estimated the total harm of applying this threshold to the cohort, and to hypothetical settings with different disease prevalence.

Results  The threshold was computed at 0.026, suggesting treatment for all patients of the cohort. Hypothetically lowering the prevalence showed that the lowest total harm in the cohort always coincides with this threshold, but that numbers of treated patients drop considerably.

Conclusion  For pulmonary tuberculosis a decision threshold solely based on utilities without cost or regret leads to a very low threshold. The lowest total harm is found always at this disease probability, irrespective of the distribution of the patients. Although these findings might suggest an excess prescription at reference level, this is not the case in settings with lower prevalence.
Individualized care scale – nurse version: a Finnish validation study
Authors: Suhonen Riitta , Gustafsson Marja‐Liisa , Katajisto Jouko , Välimäki Maritta , Leino‐Kilpi Helena
Published: January 2010

Rationale  Nurses' work is inextricably linked to the evaluation of the quality of care provision in health care. Within this evaluation, individualized care is a topical theme in western countries. Currently, there is no suitable instrument to measure the level of individualized care from the nurses' point of view.

Aim  To report the development process of the individualized care scale – nurse (ICS‐Nurse) and to ensure its validity and reliability.

Methods  A methodological design was used. Data were obtained from 544 nurses (N = 923, response rate 59%) from inpatient wards in one university, two regional and two psychiatric hospitals as well as four health centres. Three expert analyses were used to ensure content validity. Cronbach's alpha coefficients and item analysis were used to examine internal consistency reliability. A principal components analysis, Spearman's correlation coefficients, multiple regression analysis and structural equation modelled by LISREL were conducted to evaluate construct validity.

Results  The expert analyses provided good content validity evidence. The ICS‐Nurse was easy to administer and able to be completed quickly. There were few missing data. Cronbach's alpha coefficients ranged 0.72–0.84. All item‐to‐total correlations were acceptable (>0.30), but some of the inter‐item correlations were high. The principal components analysis supported the three‐component structure explaining 52% of the variance in ICS‐A‐Nurse and 56% in ICS‐B‐Nurse. LISREL supported the theoretical model.

Conclusions  The ICS‐Nurse is a valid and reliable instrument that can be used to measure nurses' perceptions of individualized nursing care in inpatient wards. There is a need to test instrument further, both nationally and internationally.
Degradation of the TBC system during the static oxidation test
Authors: MOSKAL G. , SWADŹBA L. , MENDALA B. , GÓRAL M. , HETMAŃCZYK M.
Published: January 2010

This study was done on the IN‐738 type alloy with thermal barrier coatings. On the basic surface of the NiCoCrAlY superalloy, VPS‐sprayed powder was applied as the bond‐coat. In addition, ZrO2× 8%Y2O3 powder was used for a deposition outside the top surface of a ceramic layer by the APS method. Appropriate control of the spraying process parameters permitted to obtain a gradient of porosity on the thickness of the ceramic coating. Then a static oxidation test at 1100°C and for 1100 h was performed. The basic conclusions of that testing showed that main degradation modes of the gradient thermal barrier coating system were connected with formation of porous NiAl2O4 oxides in the thermally grown oxide area and, consequently, formation of micro‐cracks, delamination of a ceramic layer and final spallation of a ceramic top‐coat.
Microstructure of friction stir welded joints of 2017A aluminium alloy sheets
Authors: MROCZKA K. , DUTKIEWICZ J. , PIETRAS A.
Published: January 2010

The present study examines a friction stir welded 2017A aluminium alloy. Transmission electron microscope investigations of the weld nugget revealed the average grain size of 5 μm, moderate density of dislocations as well as the presence of nanometric precipitates located mostly in grains interiors. Scanning electron microscope observations of fractures showed the presence of ductile fracture in the region of the weld nugget with brittle precipitates in the lower part. The microhardness analysis performed on the cross‐section of the joints showed fairly small changes; however, after the artificial ageing process an increase in hardness was observed. The change of the joint hardness subject to the ageing process indicates partial supersaturation in the material during friction stir welding and higher precipitation hardening of the joint.
State‐Dependent Plasticity in Vasopressin Neurones: Dehydration‐Induced Changes in Activity Patterning
Authors: Scott V. , Brown C. H.
Published: January 2010

Moderate dehydration impairs concentration and co‐ordination, whereas severe dehydration can cause seizures, brain damage or death. To slow the progression of dehydration until body fluids can be replenished by drinking, the increased body fluid osmolality associated with dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland. Increased vasopressin secretion reduces water loss in the urine by promoting water reabsorption in the collecting ducts of the kidney. Vasopressin secretion is largely determined by action potential discharge in vasopressin neurones, and depends on both the rate and pattern of discharge. Vasopressin neurone activity depends on intrinsic and extrinsic mechanisms. We review recent advances in our understanding of the physiological regulation of vasopressin neurone activity patterning and the mechanisms by which this is altered to cope with the increased secretory demands of dehydration.
Change of HA molecular size and boundary lubrication in synovial fluid of patients with temporomandibular disorders
Authors: WEI L. , XIONG H. , LI B. , GONG Z. , LI J. , CAI H. , MENG Q. , LONG X.
Published: January 2010

Summary  The collapse of lubrication function caused by changes of synovial fluid (SF) is regarded as the main aetiology of temporomandibular disorders (TMD). Hyaluronan (HA) is one of the principal components of SF. Both physicochemical properties and cell biological functions of HA mainly depend on its molecular size. The present study was designed to analyse the HA molecular size and boundary‐lubricating ability of SF in the patients with TMD and compare them with that from normal controls. Temporomandibular disorders patients were divided into three subgroups: displaced disc with reduction (DDR), disc without reduction (DDNR) and disc perforation (DP). After obtaining SF samples, we analysed the molecular size of HA by high‐performance liquid chromatography, and boundary‐lubricating ability (coefficient of friction, COF) of SF by a friction apparatus. The results suggested that there was no significant difference in molecular size of HA among the groups of health control, DDR and DDNR, while the DP group presented a lower molecular size when compared to other ones. Boundary‐lubricating ability test showed that COF of SF in TMD patients were significantly higher than that of healthy controls. In the patients’ subgroups, no statistical difference was observed between the group of DDR and DDNR, while DP group presented a higher COF when compared to the group of DDR or/and DDNR. Collectively, the increased values of COF, which corresponded to the decrease of HA molecular size, indicated that the distinct changes of HA molecular size and boundary‐lubricating ability in the SF occurred with TMD.
Anatomical location of various condylar points for jaw movement analysis in Japanese women
Authors: TOKIWA H. , NAKAZAWA F. , OZAKI M. , NAKAMURA Y.
Published: January 2010

Summary  The aim of this study was to determine anatomical locations of the hinge axis point, kinematic axis point and reference point for the palpated lateral condylar pole on lateral cephalograms. Subjects comprised 18 Japanese women selected according to following criteria: normal occlusion; and absence of signs and symptoms of stomatognathic function. Jaw movement and the condylar reference points noted earlier were recorded three‐dimensionally with six degrees of freedom, and kinematic axis point and hinge axis point were determined using an optoelectronic jaw‐tracking system. Lateral cephalograms were used to determine anatomical locations of the three points in the condyle. Mean location of hinge axis point was 12·9 mm anterior of the porion and 5·3 mm inferior to the Frankfort horizontal plane, the kinematic axis point was situated in 12·8 mm anterior and 0·1 mm inferior, and the reference point for the palpated lateral condylar pole was situated 10·7 mm anterior and 0·8 mm inferior, respectively. The kinematic axis point was located outside the condyle in the majority of subjects. The reference point for the palpated lateral pole offers a useful indicator in the analysis of condylar movements.
The evolution from females to hermaphrodites results in a sexual conflict over mating in androdioecious nematode worms and clam shrimp
Authors: Chasnov J. R.
Published: January 2010

The nematode worm Caenorhabditis elegans and the clam shrimp Eulimnadia texana are two well-studied androdioecious species consisting mostly of self-fertilizing hermaphrodites and few males. To understand how androdioecy can evolve, a simple two-step mathematical model of the evolutionary pathway from a male–female species to a selfing-hermaphrodite species is constructed. First, the frequency of mutant females capable of facultative self-fertilization increases if the benefits of reproductive assurance exceed the cost. Second, hermaphrodites become obligate self-fertilizers if the fitness of selfed offspring exceeds one-half the fitness of outcrossed offspring. Genetic considerations specific to C. elegans and E. texana show that males may endure as descendants of the ancestral male–female species. These models combined with an extensive literature review suggest a sexual conflict over mating in these androdioecious species: selection favours hermaphrodites that self and males that outcross. The strength of selection on hermaphrodites and males differs, however. Males that fail to outcross suffer a genetic death. Hermaphrodites may never encounter a rare male, and those that do and outcross only bear less fecund offspring. This asymmetric sexual conflict results in an evolutionary stand-off: rare, but persistent males occasionally fertilize common, but reluctant hermaphrodites. A consequence of this stand-off may be an increase in the longevity of the androdioecious mating system.
Phylogenetically structured variance in felid bite force: the role of phylogeny in the evolution of biting performance
Authors: Sakamoto M. , Lloyd G. T. , Benton M. J.
Published: January 2010

A key question in evolution is the degree to which morphofunctional complexes are constrained by phylogeny. We investigated the role of phylogeny in the evolution of biting performance, quantified as bite forces, using phylogenetic eigenvector regression. Results indicate that there are strong phylogenetic signals in both absolute and size-adjusted bite forces, although it is weaker in the latter. This indicates that elimination of size influences reduces the level of phylogenetic inertia and that the majority of the phylogenetic constraint is a result of size. Tracing the evolution of bite force through phylogeny by character optimization also supports this notion, in that relative bite force is randomly distributed across phylogeny whereas absolute bite force diverges according to clade. The nonphylogenetically structured variance in bite force could not be sufficiently explained by species-unique morphology or by ecology. This study demonstrates the difficulties in identifying causes of nonphylogenetically structured variance in morphofunctional character complexes.
Giving offspring a head start in life: field and experimental evidence for selection on maternal basking behaviour in lizards
Authors: Wapstra E. , Uller T. , While G. M. , Olsson M. , Shine R.
Published: January 2010

The timing of birth is often correlated with offspring fitness in animals, but experimental studies that disentangle direct effects of parturition date and indirect effects mediated via variation in female traits are rare. In viviparous ectotherms, parturition date is largely driven by female thermal conditions, particularly maternal basking strategies. Our field and laboratory studies of a viviparous lizard (Niveoscincus ocellatus) show that earlier-born offspring are more likely to survive through their first winter and are larger following that winter, than are later-born conspecifics. Thus, the association between parturition date and offspring fitness is causal, rather than reflecting an underlying correlation between parturition date and maternal attributes. Survival selection on offspring confers a significant advantage for increased maternal basking in this species, mediated through fitness advantages of earlier parturition. We discuss the roles of environmentally imposed constraints and parent–offspring conflict in the evolution of maternal effects on parturition date.
No heightened condition dependence of zebra finch ornaments – a quantitative genetic approach
Authors: Bolund E. , Schielzeth H. , Forstmeier W.
Published: January 2010

The developmental stress hypothesis offers a mechanism to maintain honesty of sexually selected ornaments, because only high quality individuals will be able to develop full ornamentation in the face of stress during early development. Experimental tests of this hypothesis have traditionally involved the manipulation of one aspect of the rearing conditions and an examination of effects on adult traits. Here, we instead use a statistically powerful quantitative genetic approach to detect condition dependence. We use animal models to estimate environmental correlations between a measure of early growth and adult traits. This way, we could make use of the sometimes dramatic differences in early growth of more than 800 individually cross-fostered birds and measure the effect on a total of 23 different traits after birds reached maturity. We find strong effects of environmental growth conditions on adult body size, body mass and fat deposition, moderate effects on beak colour in both sexes, but no effect on song and plumage characters. Rather surprisingly, there was no effect on male attractiveness, both measured in mate choice trials and under socially complex conditions in aviaries. There was a trend for a positive effect of good growth conditions on the success at fertilizing eggs in males breeding in aviaries whereas longevity was not affected in either sex. We conclude that zebra finches are remarkably resilient to food shortage during growth and can compensate for poor growth conditions without much apparent life-history trade-offs. Our results do not support the hypothesis that sexually selected traits show heightened condition dependence compared to nonsexually selected traits.
Association with TGF‐β1 Gene Polymorphisms and Reproductive Performance of Large White Pig
Authors: Wu YP , Wang AG , Li N , Fu JL , Zhao XB
Published: January 2010

Contents

As a multifunctional cytokine, transforming growth factor‐beta1 (TGF‐β1) was detected in the utero‐placental interface during early pregnancy in the pig and believed to enhance trophoblast attachment to the endometrium. In this experiment, we selected TGF‐β1 as the candidate gene affecting litter size in pigs. Four polymorphic loci of TGF‐β1 gene were found by PCR‐SSCP (single‐strand conformation polymorphism) in Large white sows (n = 567): C→T mutation at 33nt in the intron 4; G→A mutation at 179nt in the intron 6; C→T mutation at 1043nt in the intron 6; GG→AA linkage mutations at 2490nt and 2494nt respectively. We haplotyped these SNPs as: CGCAA (denote as P) and TATGG (denote as K). The effects of three haplotypic combinations (HCs) of PP, PK and KK on litter sizes were investigated by a linear model. It was found that for the first parity litters, the least squares mean for total number born (TNB) of KK was 1.02 piglets/litter, higher than that of PK (p < 0.05), 0.49 piglets/litter higher than that of PP (p > 0.1). There were no significant differences between HCs on the second parity. The result indicated that KK HCs was significantly associated with pig litter size.
Comparison of Different Cryopreservation Techniques: Higher Survival and Implantation Rate of Frozen–Thawed Mouse Pronuclear Embryos in the Presence of Beta‐Mercaptoethanol in Post‐Thaw Culture
Authors: Bagis H , Akkoc T , Taskin C , Arat S
Published: January 2010

Contents

The objective of this study was to investigate the effects of beta‐mercaptoethanol (β‐ME) on post‐thaw embryo developmental competence and implantation rate of mouse pronuclear (PN) embryos that were cryopreserved after slow freezing, solid surface vitrification (SSV) or open‐pulled straw (OPS) vitrification methods. Mouse PN embryos were cryopreserved by using slow freezing, SSV and OPS methods. After cryopreservation, freeze–thawed PN embryos were cultured up to blastocyst stage in a defined medium supplemented without or with 50 μmβ‐ME. The blastocyst formation rate of embryos that were cryopreserved by slow freezing method (40.0%) or vitrified by OPS method (18.3%) were lower than those vitrified by SSV method (55.6%) and fresh embryos (61.9%) in the absence of 50 β‐ME in the culture media (p < 0.05). The blastocyst formation rate of embryos that were cryopreserved by slow freezing method (53.1%) or by OPS method (41.9%) were lower than those vitrified by SSV method (79.5%) and that of fresh (85.7%) in the presence of β‐ME in the culture media (p < 0.05). The embryos transfer results revealed that the implantation rate of blastocyst derived from mouse PN embryos vitrified by SSV method (31.9% vs 51.2%) was similar to that of the control (39.0% vs 52.5%), but higher than those cryopreserved by slow freezing (28.2% vs 52.0%) and by OPS method (0.0% vs 51.2%) (p < 0.05). In conclusion, supplementation of β‐ME in an in vitro culture medium was shown to increase survival of embryo development and implantation rate of frozen–thawed mouse PN embryos after different cryopreservation protocols.
Alkaline and Acid Phosphatase, β‐Glucuronidase and Electrolyte Levels in Fractionated Stallion Ejaculates
Authors: Kareskoski AM , Reilas T , Sankari S , Andersson M , Güvenc K , Katila T
Published: January 2010

Contents

Seminal plasma (SP) is a mixture of contents from the testes, epididymides and accessory sex glands. The sperm concentration is highest in the first few jets, or fractions, of the ejaculate, and the composition of SP varies between these fractions because accessory gland secretions are released in a specific order. The aim of this study was to compare the levels of Na, Cl, K, Mg, Ca, inorganic phosphate (Pi) and the enzymes alkaline phosphatase (AP), acid phosphatase (ACP) and β‐glucuronidase (BG) in the different fractions of the ejaculate and in different stallions. All semen collections were done using a computer‐controlled phantom that collects the ejaculatory jets separately in five cups. The cups with the highest (HIGH) and the lowest (LOW) sperm concentration were analysed. In Trial I, semen was collected from three reproductively normal stallions. In Trial II, ejaculates of two reproductively normal stallions were compared to those of two subfertile stallions. In Trial III, semen was collected from seven stallions with varying reproductive history. The sperm‐rich fractions contained the highest levels of AP, ACP, BG and inorganic phosphate, and the values were positively correlated to the sperm concentration. Significant differences between the subfertile and the fertile stallions pairs in HIGH : LOW ratios were found in Pi and Cl concentrations. The highest concentrations of Ca and Mg were found in the last fractions with low sperm concentrations, with no significant differences between the fertile and the subfertile stallion pairs. The concentrations of K, Na and Cl were similar in HIGH and LOW fractions and in whole ejaculate samples. Pre‐sperm fluid contained the highest concentrations of Na and Cl. Some of the possible variation in storage tolerance between ejaculates and ejaculatory fractions could perhaps be explained by differences in the composition of SP.
Prevalence of erosive esophagitis among Japanese patients taking low‐dose aspirin
Authors: Yamamoto Takatsugu , Mishina Yuji , Ebato Tadahisa , Isono Akari , Abe Koichiro , Hattori Kengo , Ishii Taro , Kuyama Yasushi
Published: January 2010

Background and Aim:  The risk for erosive esophagitis (EE) with low‐dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA.

Methods:  From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 ± 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age‐ and sex‐matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well‐experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers.

Results:  The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7–3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5–8.8).

Conclusion:  In Japanese patients taking ASA, EE was not as common as peptic ulcers.
Comparison of temporary stent insertion with pneumatic dilation of the same diameter in the treatment of achalasia patients: A retrospective study
Authors: Zhu Yue‐Qi , Cheng Ying‐Sheng , Tang Guang‐Yu , Li Ming‐Hua , Zhao Jun‐Gong , Li Feng
Published: January 2010

Background and Aim:  To retrospectively analyze and compare the clinical efficacy of temporary stent insertion with pneumatic dilation of the same diameter in the treatment of achalasia based on a long‐term follow up.

Methods:  A total of 101 treated achalasia patients were divided into a pneumatic dilation group (Group A, n = 38) and a temporary stent insertion group (Group B, n = 63). The diameter of the balloon or stent used was 30 mm. The total symptom scores (TSS) and esophageal manometry were used to assess the symptoms and lower esophageal sphincter (LES) pressure improvement. Barium swallow–esophageal studies were used to assess esophageal emptying objectively. TSS and LES pressure improvement were assessed, recorded, and compared during the regular interval follow up.

Results:  Forty‐nine pneumatic dilations and 65 stent insertions were successfully performed in all patients under fluoroscopy. Complications included pain, reflux, and bleeding, which occurred in nine (23.6%), eight (21.1%), and three (8%) patients in Group A, and in 27 (42.9%), eight (12.7%), and 10 (15.9%) patients in Group B, respectively. The stent was retained approximately 4–7 days and was retrieved via endoscope. TSS, esophageal manometry, and barium esophagram post‐treatment significantly improved compared to those given pretreatment (P < 0.0001). At the end of follow up, TSS and LES pressure in Group B were 4.00 ± 1.00 and 43.67 ± 12.66 mmHg, compared to 10.20 ± 0.45 (P = 0.0096) and 58.60 ± 8.65 mmHg (P = 0.1687) in Group A. The Kaplan–Meier method revealed better symptom remission in Group B compared to Group A (log–rank test, P = 0.0212).

Conclusion:  Retrievable stent placement is more effective than the same diameter pneumatic dilation for the treatment of achalasia with a long‐term follow up.
Successful stenting in ductal disruption favorably impacts treatment outcomes in patients undergoing transmural drainage of peripancreatic fluid collections
Authors: Trevino Jessica M , Tamhane Ashutosh , Varadarajulu Shyam
Published: January 2010

Background and Aim:  The role of pancreatic duct (PD) stenting in patients undergoing endoscopic transmural drainage of peripancreatic fluid collection (PFC) remains unclear. The objective of this study is to evaluate the effect of PD stenting on treatment success in patients undergoing endoscopic transmural drainage of PFC.

Methods:  This is a retrospective follow‐up study of all patients who underwent endoscopic and endoscopic ultrasonography‐guided transmural drainage of PFC during a 5‐year period. Double‐pigtail stents were deployed in all patients; in addition, nasocystic catheters were deployed in those with abscess/necrosis. An endoscopic retrograde cholangiopancreatogram was attempted whenever feasible in all patients, and pancreatic stents were placed when the duct disruption could be bridged. Success was defined as an improvement in symptoms and resolution of PFC upon follow‐up computed tomography at 8 weeks.

Results:  Of the 110 patients who underwent PFC drainage, 40 (36%) underwent simultaneous PD stenting. Treatment was successful in 95 of the 110 patients (86%). The PFC types were: pseudocyst (62%), necrosis (20%), and abscess (18%). The median duration of follow up was 9.9 months. Those who underwent PD stenting were significantly more likely to have treatment success than those who did not undergo PD stenting (97.5% vs 80%; risk ratio [RR]crude = 1.48, P = 0.01). In the multivariable analysis, this association remained significant (RRadjusted = 1.14, 95% confidence interval: 1.01–1.29, P = 0.036), even after adjusting for the etiology of pancreatitis, type and location of PFC, luminal compression at endoscopy, enteral nutrition, white blood cell count, and number of endoscopic interventions.

Conclusions:  Transpapillary PD stenting improves treatment outcomes in patients undergoing endoscopic transmural drainage of PFC.
Diagnostic accuracy of multidetector‐row computed tomography for hilar cholangiocarcinoma
Authors: Akamatsu Nobuhisa , Sugawara Yasuhiko , Osada Hisato , Okada Takenori , Itoyama Shinji , Komagome Masahiko , Shin Nobuhiro , Cho Narihiro , Ishida Takashi , Ozawa Fumiaki , Hashimoto Daijo
Published: January 2010

Background and Aim:  The aim of this study was to investigate the diagnostic reliability of multidetector‐row computed tomography (MDCT) for the evaluation of tumor spread in hilar cholangiocarcinoma.

Methods:  Images obtained from a 16‐detector row scanner of 22 patients were interpreted. The diagnostic accuracy of longitudinal ductal spread, vertical invasion (including hepatic parenchyma), and lymph node metastasis was assessed with reference to histopathological findings.

Results:  The location of the tumor was correctly diagnosed in 95% of cases (21/22), but in five of these cases, the cut end of the intrahepatic bile duct was positive, resulting in 77% diagnostic accuracy for longitudinal spread. Among the patients with a negative bile duct surgical margin, there was a significant difference in the measurement of tumor spread between MDCT and microscopic investigation (P < 0.001). For vertical invasion, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDCT were 69%, 100%, 100%, and 69% for the liver parenchyma, respectively. The sensitivity, specificity, PPV, and NPV of MDCT for lymph node metastasis were 50%, 75%, 43%, and 80%, respectively.

Conclusions:  The diagnostic accuracy of MDCT for tumor location and vertical invasion was satisfactory, but ductal spread was underestimated in comparison with microscopic measurements.
Investigation of doublecortin and calcium/calmodulin‐dependent protein kinase‐like‐1‐expressing cells in the mouse stomach
Authors: Zhang Yan , Huang Xinlan
Published: January 2010

Background and Aims:  For lack of a definite stem cell marker, there is limited knowledge of the precise location and fate of stem cells after injury. Doublecortin and calcium/calmodulin‐dependent protein kinase‐like‐1 (DCAMKL‐1) is a putative intestinal and colon stem cell marker. Our aim was to identify DCAMKL‐1‐expressing cells in the gastric epithelium and to analyze the fate of DCAMKL‐1‐expressing cells during gastric mucosal injury and repair.

Methods:  Acidified ethanol was administered to wild‐type mice. DCAMKL‐1 expression were detected by immunohistochemistry and western blotting.

Results:  There were some DCAMKL‐1‐expressing cells in normal mouse stomachs. All the cells were located in the gastric isthmus region. All DCAMKL‐1‐expressing cells were double stained with Dolichos biflorus lectin‐expressing parietal cells and Musashi‐1‐expressing cells. The DCAMKL‐1 antigen expression decreased 12 h after injury and gradually increased to normal 4 d after injury.

Conclusion:  Using DCAMKL‐1 as a marker for stomach stem cells, we could describe the expression pattern of stomach stem cells during mucosal injury.
Relationship of non‐alcoholic fatty liver disease to colorectal adenomatous polyps
Authors: Hwang Sang Tae , Cho Yong Kyun , Park Jung Ho , Kim Hong Joo , Park Dong Il , Sohn Chong Il , Jeon Woo Kyu , Kim Byung Ik , Won Kyoung Hee , Jin Wook
Published: January 2010

Background and Aims:  Metabolic syndrome and insulin resistance are associated with a higher risk of colon cancer. Non‐alcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome in the liver. This investigation was initiated to determine whether NAFLD has a relationship to colorectal adenomatous polyps.

Methods:  We examined the 2917 participants who underwent a routine colonoscopy at Kangbuk Samsung Hospital in 2007. We divided the 2917 subjects into the adenomatous polyp group (n = 556) and the normal group (n = 2361). Anthropometric measurements, biochemical tests for liver and metabolic function, and abdominal ultrasonographs were assessed.

Results:  The prevalence of NAFLD was 41.5% in the adenomatous polyp group and 30.2% in the control group. By multiple logistic regression analysis, NAFLD was found to be associated with an increased risk of colorectal adenomatous polyps (odds ratio, 1.28; 95% confidence interval, 1.03–1.60). An increased risk for NAFLD was more evident in patients with a greater number of adenomatous polyps.

Conclusion:  NAFLD was associated with colorectal adenomatous polyps. Further studies are needed to confirm whether NAFLD is a predictor for the development of colorectal adenomatous polyps and cancer.
Radiotherapy for hepatocellular carcinoma: Systematic review of radiobiology and modeling projections indicate reconsideration of its use
Authors: Wigg Alan J , Palumbo Kevin , Wigg David R
Published: January 2010

Background and Aims:  External beam radiotherapy currently has a limited role in the treatment of hepatocellular carcinoma (HCC). The purpose of this article was to review available radiobiological data on HCC and normal liver and incorporate these data into radiobiological models that may be used to explain and improve treatment.

Methods:  Volume doubling times of HCC were described and used to demonstrate growth of HCC with time, assuming both exponential and logistic growth. Radiosensitivity of HCC was described and used to demonstrate the probability of uncomplicated tumor control as tumor size increases. The relationship between tolerance of liver to irradiation and volume irradiated was examined.

Results:  The median volume doubling time for untreated HCC was 130 days. HCC have a long period of subclinical growth. Radiosensitivity of HCC lies within the range of other tumors commonly treated with radiotherapy. When treating small volumes of normal liver, relatively high doses may be used with low risk of late radiation damage. There is a high probability of sterilizing subclinical disease and small HCC with tolerable radiation doses.

Conclusion:  New radiobiological data, modeling, emerging clinical data and the advantages offered by standard external beam radiotherapy techniques suggest the need for reconsidering the use of radiotherapy and for new trials.
Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1
Authors: Pal Sampa , Polyak Stephen J , Bano Nazneen , Qiu Wan Chong , Carithers Robert L , Shuhart Margaret , Gretch David R , Das Aditi
Published: January 2010

Background and Aims:  Hepatitis C virus (HCV)‐induced chronic inflammation may induce oxidative stress which could compromise the repair of damaged DNA, rendering cells more susceptible to spontaneous or mutagen‐induced alterations, the underlying cause of liver cirrhosis and hepatocellular carcinoma. In the current study we examined the induction of reactive oxygen species (ROS) resulting from HCV infection and evaluated its effect on the host DNA damage and repair machinery.

Methods:  HCV infected human hepatoma cells were analyzed to determine (i) ROS, (ii) 8‐oxoG and (iii) DNA glycosylases NEIL1, NEIL2, OGG1. Liver biopsies were analyzed for NEIL1.

Results:  Human hepatoma cells infected with HCV JFH‐1 showed 30–60‐fold increases in ROS levels compared to uninfected cells. Levels of the oxidatively modified guanosine base 8‐oxoguanine (8‐oxoG) were significantly increased sixfold in the HCV‐infected cells. Because DNA glycosylases are the enzymes that remove oxidized nucleotides, their expression in HCV‐infected cells was analyzed. NEIL1 but not OGG1 or NEIL2 gene expression was impaired in HCV‐infected cells. In accordance, we found reduced glycosylase (NEIL1‐specific) activity in HCV‐infected cells. The antioxidant N‐acetyl cystein (NAC) efficiently reversed the NEIL1 repression by inhibiting ROS induction by HCV. NEIL1 expression was also partly restored when virus‐infected cells were treated with interferon (IFN). HCV core and to a lesser extent NS3‐4a and NS5A induced ROS, and downregulated NEIL1 expression. Liver biopsy specimens showed significant impairment of NEIL1 levels in HCV‐infected patients with advanced liver disease compared to patients with no disease.

Conclusion:  Collectively, the data indicate that HCV induction of ROS and perturbation of NEIL1 expression may be mechanistically involved in progression of liver disease and suggest that antioxidant and antiviral therapies can reverse these deleterious effects of HCV in part by restoring function of the DNA repair enzyme/s.
Trend of colorectal cancer in Hong Kong: 1983–2006
Authors: Yee Yuk Kei , Gu Qing , Hung Ivan , Tan Victoria PY , Chan Pierre , Hsu Axel , Pang Roberta , Lam Colin SC , Wong Benjamin CY
Published: January 2010

Background and Aim:  The incidence of colorectal cancer (CC) is increasing in many Asian countries, but decreasing in western countries. The present study examined the local incidence of CC in the past few decades.

Methods:  A population based study, using data from Hong Kong (HK) Cancer Registry, was carried out to examine the trends of CC in different age groups in HK. Comparison with other countries was made.

Results:  The crude rate of CC in HK increased from 29.6/100 000 in 1983 to 57.1/100 000 in 2006. Age standardized rate (ASR) increased by less than 20%. It was markedly smaller than the 190% increase in crude rate. ASR progressively increased in males. In females, ASR peaked in 1994 and declined in the last decade. In most countries, the risk of CC was higher and increasing in males, but stable or decreasing in females. With respect to age, increasing risk was noted in males above 60 years old and females above 70 years old. However, a declining rate was noted in those below 50 years old. The decrease was over 40% in the 30–34 years group over the past two decades.

Conclusions:  Increasing incidence of CC in HK was mostly in the older and male population, but not in the younger age group.
Bugs and irritable bowel syndrome: The good, the bad and the ugly
Authors: Ghoshal Uday C , Park Hyojin , Gwee Kok‐Ann
Published: January 2010

Recently, there has been strong interest in the therapeutic potential of probiotics for irritable bowel syndrome (IBS). At the same time, there is a rapidly growing body of evidence to support an etiological role for gastrointestinal infection and the associated immune activation in the development of post‐infectious IBS. In a more controversial area, small intestinal bacterial overgrowth has been associated with a subset of patients with IBS; the issue of whether it is appropriate to treat a subset of IBS patients with antibiotics and probiotics is currently a matter for debate. Thus, it appears that the gastrointestinal microbial flora may exert beneficial effects for symptoms of IBS under some circumstances, while in other situations gut microbes could give rise to symptoms of IBS. How do we make sense of the apparently diverse roles that ‘bugs’ may play in IBS? To address this question, we have conducted an in‐depth review, attempting where possible to draw lessons from Asian studies.
Effect of biotherapeutics on cyclosporin‐inducedClostridium difficileinfection in mice
Authors: Kaur Sukhminderjit , Vaishnavi Chetana , Ray Pallab , Kochhar Rakesh , Prasad Kaushal Kishor
Published: January 2010

Background and Aim: Immunosuppressive therapy may precipitateClostridium difficileassociated disease (CDAD). We evaluated the role of cyclosporin in the development of CDAD in the experimental mouse model and studied the effect of probiotic and epidermal growth factor (EGF) as biotherapeutics measures.

Methods: BALB/c mice (n = 24) were divided into four groups. Group I animals not given any inoculum served as controls. Animals in the remaining three groups (Group II, III and IV) were given cyclosporin daily from days 1–7 followed byC. difficileinoculum on day 8. Additionally, the animals receivedLactobacillus acidophilus(Group III) and EGF (Group IV) for one‐week postC. difficilechallenge. The animals were evaluated for colonization and toxin production byC. difficile, myeloperoxidase (MPO) activity and histopathological changes.

Results: Clostridium difficilewas colonized and elaborated its toxins in animals receiving cyclosporin andC. difficile. MPO activity was significantly higher (P < 0.05) and histopathological epithelial damage, cryptitis and acute inflammatory changes were seen in the cecum and colon.C. difficilecount, toxins A and B titers and MPO activity were significantly lowered (P < 0.05) in animals receiving probiotic and EGF. Histopathologically, mucodepletion and inflammatory infiltrate were decreased in the biotherapeutic receiving animals.

Conclusions: Cyclosporin led to the development of mild to moderate CDAD in animals. Administration of biotherapeutics reduced the severity of CDAD. Future clinical trials are needed for further investigation of these potential biotherapeutic measures.
Prevalence of Helicobacter pylori infection in duodenal ulcer and gastro‐duodenal ulcer diseases in Taiwan
Authors: Chen Tseng‐Shing , Luo Jiing‐Chyuan , Chang Full‐Young
Published: January 2010

Background and Aim:  The prevalence of Helicobacter pylori‐negative duodenal ulcer (DU) is increasing in Western countries but is rare in Japan. We aimed to examine the prevalence of H. pylori infection and the characteristics in DU and gastro‐duodenal ulcer (GDU) diseases in Taiwan.

Study:  All patients with an endoscopic diagnosis of DU or GDU from September 2003 to May 2004 at Taipei Veterans General Hospital were included. Rapid urease test was done for all patients, while urea breath test was carried out on those with negative rapid urease tests. A patient was considered infected if either test was positive.

Results:  The prevalence of H. pylori was 88.7% (555/626) in DU and 90.5% (95/105) in GDU patients. There was no difference in sex and prevalence of H. pylori between the two groups but age was higher in the GDU patients (60.1 ± 15.5 vs. 55.4 ± 15.5, P = 0.005). Of H. pylori‐negative DU patients, 28.2% (20/71) reported using non‐steroidal anti‐inflammatory drugs (NSAIDs)/aspirin, which were used by all 10 H. pylori‐negative GDU patients (100%) (P < 0.001). There was no difference in sex and age between H. pylori‐positive and negative DU patients. The prevalence rate of H. pylori in DU was not statistically different among outpatients, inpatients, and physical check‐up subjects (86.8% vs. 93.3% vs. 90.7%, P = 0.163).

Conclusion:  The prevalence of H. pylori infection in DU appears to be decreasing in Taiwan. Thus, eradication therapy without confirming the presence of H. pylori in DU patients cannot be recommended. NSAIDs/aspirin is the major risk factor for H. pylori‐negative DU patients, especially those with co‐morbid gastric ulcer.
Long‐term results of balloon‐occluded retrograde transvenous obliteration for gastric fundal varices: Hepatic deterioration links to portosystemic shunt syndrome
Authors: Kumamoto Masafumi , Toyonaga Atsushi , Inoue Hiroto , Miyakoda Kenji , Morita Yukihiko , Emori Keigo , Sakamoto Yoshihiro , Oho Kazuhiko , Sata Michio
Published: January 2010

Background and Aims:  It is well known that a large portosystemic shunt develops during portal hypertension. In this study, we studied the long‐term effects of a large splenorenal shunt (SRS) on liver function and survival.

Methods:  The subjects were divided into three groups: an SRS (−) group consisting of cirrhotic patients without SRS; an SRS (+) group consisting of patients with gastric fundal varices and SRS; and a balloon‐occluded retrograde transvenous obliteration (B‐RTO) group with a completely obliterated SRS by B‐RTO. We compared the following among these groups: the total bilirubin levels, serum albumin levels, prothrombin times, changes in Child–Pugh scores, and survival rates.

Results:  After a 3‐year follow‐up period the Child–Pugh scores showed significant differences among the SRS (+), SRS (−), and B‐RTO groups. The score worsened for the SRS (+) group. The cumulative survival rates were significantly different between the SRS (+) and SRS (−) groups and between the SRS (+) and B‐RTO groups. The vital prognosis worsened for the SRS (+) group.

Conclusions:  The presence of a large splenorenal shunt (portosystemic shunt) was indicated to lower liver function and vital prognosis. B‐RTO, which completely obliterates large splenorenal shunts, inhibited the lowering of hepatic functional reserve and the worsening of vital prognosis, indicating a protective role. Liver pathology and the presence of a large portosystemic shunt each separately result in progressive liver dysfunction and worsen the survival rate. We found that such a pathological condition had occurred due to a large portosystemic shunt, and it should be called ‘portosystemic shunt syndrome.’