bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoregulation therapy changes the frequency of interleukin (IL)-22+CD4+T cells in systemic lupus erythematosus patients
Authors: Zhao L , Ma H , Jiang Z , Jiang Y , Ma N
Published: March 2014

T cell and T cell-related cytokine abnormalities are involved in the pathogenesis of systemic lupus erythematosus (SLE). Our previous study showed that the interleukin (IL)-22+CD4+T cells and IL-22 play an important role in the pathogenesis of SLE. In this study, we aimed to investigate the effects of glucocorticoids (GCs) and immunodepressant agents on IL-22 and IL-22-producing T cell subsets in SLE patients. The frequencies of peripheral blood T helper type 22 (Th22), IL-22+Th17, IL-22+Th1 and Th17 cells and the concentrations of serum IL-22, IL-17 and interferon (IFN)-γ in SLE patients receiving 4 weeks of treatment with cyclophosphamide (CYC), methylprednisolone and hydroxychloroquine (HCQ) were characterized by flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA). The frequencies of Th22, IL-22+Th17 and Th17 cells and the concentrations of IL-22 and IL-17 were reduced in response to the drugs methylprednisolone, cyclophosphamide and hydroxychloroquine for 4 weeks in the majority of SLE patients. However, the percentage of Th1 cells showed no change. No differences in the levels of IL-22 and IL-22+CD4+ T cells were found between non-responders and health controls either before or after therapy. IL-22 levels were correlated positively with Th22 cells in SLE patients after treatment. These results suggest that elevated IL-22 is correlated with IL-22+CD4+T cells, especially Th22 cells, and may have a co-operative or synergetic function in the immunopathogenesis of SLE. GC, CYC and HCQ treatment may regulate the production of IL-22, possibly by correcting the IL-22+CD4+T cells polarizations in SLE, thus providing new insights into the mechanism of GC, CYC and HCQ in the treatment of SLE.
Frequency and clonality of peripheral γδ T cells in psoriasis patients receiving anti-tumour necrosis factor-α therapy
Authors: Kelsen J , Dige A , Christensen M , D'Amore F , Iversen L
Published: March 2014

Hepatosplenic γδ T cell lymphoma (HSTCL) has been observed in patients with Crohn's disease (CD) who received anti-tumour necrosis factor (TNF)-α agents and thiopurines, but only one case was reported in a psoriasis patient worldwide. This difference could be due to differences in either the nature of the inflammatory diseases or in the use of immunomodulators. We investigated the impact of anti-TNF-α agents on the level and repertoire of γδ T cells in peripheral blood from psoriasis patients. Forty-five men and 10 women who were treated with anti-TNF-α agents for psoriasis were monitored for a median 11 months for the level and clonality of γδ T cells via flow cytometry and polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR-γ) gene rearrangements. Seventeen men had a repeated analysis within 48 h of the infliximab infusion to reveal a possible expansion of γδ T cells, as observed previously in CD patients. Ten psoriasis patients who were never exposed to biologicals and 20 healthy individuals served as controls. In the majority of psoriasis patients, the level and clonal pattern of γδ T cells was remarkably stable during infliximab treatment. A single male patient repeatedly experienced a significant increase in the level of γδ T cells after infliximab infusions. A monoclonal γδ T cell repertoire in a polyclonal background tended to be more frequent in anti-TNF-α-treated patients than naive patients, suggesting that anti-TNF-α therapy may promote the clonal selection of γδ T cells in psoriasis patients.
COMMERCIAL REVITALIZATION IN LOW‐INCOME URBAN COMMUNITIES: THE HOLDUP PROBLEM AND URBAN DEVELOPMENT POLICY
Authors: ZHOU LI
Published: March 2014

A commercial development model, based on Fujita's monopolistic competition model of spatial agglomeration, addresses firms' decisions to enter urban communities. The model focuses on commercial developers and large department stores, and identifies a potential holdup problem in the commercial development market arising because developers incur costs before negotiating with anchor tenants over profit sharing; the holdup problem is more likely to occur in low‐income communities where the profitability of commercial projects is small. The model predicts that direct incentives to developers are preferred to general tax incentives for addressing this market failure. (JEL R58, H50, H76)
Eye on the Taiga: Removing Global Policy Impediments to Safeguard the Boreal Forest
Authors: Moen Jon , Rist Lucy , Bishop Kevin , Chapin F. S. , Ellison David , Kuuluvainen Timo , Petersson Hans , Puettmann Klaus J. , Rayner Jeremy , Warkentin Ian G. , Bradshaw Corey J. A.
Published: March 2014

The absence of boreal forests from global policy agendas on sustainable development and climate change mitigation represents a massive missed opportunity for environmental protection. The boreal zone contains some of the world's largest pools of terrestrial carbon that, if not safeguarded from a conversion to a net source of greenhouse gases, could seriously exacerbate global climate change. At the same time, boreal countries have a strong tradition of forest management—expertise that could be effectively leveraged toward global and national carbon mitigation targets and sustainable development. Current obstacles against such contributions include weak incentives for carbon sequestration and a reluctance to embrace change by forest managers and policy makers. We discuss possible solutions to overcome these obstacles, including the improvement of ineffective incentives, the development of alternative forest management strategies, and the need to maintain ecosystem resilience through the pursuit of policy and management options.
Making it possible – interventions for children with cerebral palsy
Authors: Beckung Eva
Published: March 2014

This commentary is on the original article by Bartlett et al..
Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15‐0444)
Authors: Shon J.H. , Kim N. , Park S.J. , Oh M.K. , Kim E.Y. , Lee S.H. , Kim Y.H. , Shin J.G.
Published: March 2014

This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase‐4 (DPP‐4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end‐stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66‐fold (1.10, 1.49, 1.22 and 1.21‐fold) increase of mean area under the time‐plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non‐HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure–response relationship. Impact of HD on the removal of gemigliptin was negligible.
Variation in Trill Characteristics in Tree Pipit Songs: Different Trills for Different Use?
Authors: Petrusková Tereza , Kinštová Anna , Pišvejcová Iveta , Mula Laguna Juan , Cortezón Adrián , Brinke Tomáš , Petrusek Adam
Published: March 2014

Transmitting information about singer's quality is an important function of song in many bird species, and this information should be useful in territorial interactions. Fast trills, being physically demanding song structures, are particularly suitable candidates for signalling of quality or aggressive motivation. We have evaluated trill characteristics in songs within a population of the Tree Pipit, a common European songbird with no sexual dimorphism, in which song apparently plays a key role in territory defence as well as mate choice. Two types of relatively fast trills (each of them in multiple variants differing in complexity) were commonly observed in repertoires of Tree Pipit males. Trill rates significantly differed among individuals, suggesting that these song structures may carry information about male quality in this species. We tested by playback experiments whether both trill types are used in territorial encounters. Only one of the trill types was sung by males in response to playback, regardless on the trill type played to them. In an immediate response to playback, they increased the frequency of use of this trill, and also significantly increased the trill rate in comparison with spontaneous songs. This confirmed field observations, suggesting that this trill is important in male–male interactions. On the contrary, the use of the fastest, apparently more demanding, trill type actually decreased after the simulated territorial intrusion. We hypothesize that the latter one is more directed towards females, and that while performance of both trill types may reflect male quality, they are primarily used in different contexts.
Early Silurian ‘algal meadows’ of Anticosti Island, eastern Canada: an analogue to modern sea grass meadows?
Authors: Wang Yi , Jin Jisuo , Zhan Renbin , Copper Paul
Published: March 2014

In modern marine ecosystems, sea‐grass and chlorophyte meadows play an important ecological role by serving as a carbon sink. Despite their generally limited areal distribution, the high productivity of sea‐grass meadows makes them an efficient assimilator of CO2. During the early Palaeozoic, complex life was virtually confined to the marine environment, with algae being one of the common carbon‐fixers, alongside abundant calcifying cyanobacteria, rhodophytes, chlorophytes and charophytes, as well as non‐skeletal dinoflagellates and acritarchs. Fossil and molecular data indicate that marine thallophytic algae first appeared in the Early Proterozoic and became widespread in the Palaeozoic, although their fossil record is sporadic because of their soft‐bodied nature; in the absence of angiosperm sea grass and mangroves and poorly understood phytoplankton biomass, thallophytic algae were probably major primary producers. In this article, we suggest that thallophytic algae may have played a significant role as a carbon sink in the Early Silurian, analogous to modern sea‐grass meadows or kelp forests, based on the well‐preserved Early Silurian thallophytic algal meadow from Anticosti Island, eastern Canada.
Indicators of the Anthropocene: is there a case for conservation?
Authors: Jordan Hannah , Prosser Colin
Published: March 2014

The Earth's atmosphere, biosphere and lithosphere are increasingly being modified by human activity. Given this anthropogenic influence on the natural environment, the case for recognizing an Anthropocene Epoch has recently been made and there is ongoing debate as to whether, and how, to formally characterize and define such an epoch. As a contribution to this debate, this article explores whether or not the landscapes, deposits, landforms and key marker horizons that may be used to characterize and define an Anthropocene Epoch could, and should, be identified and conserved in the same manner as other parts of the geological succession. Anthropogenic features pose a conservation challenge, however, as they often cross cut existing conservation frameworks which tend to focus on the natural, historic or cultural environment. Developing a coherent approach to the conservation of the indicators of an Anthropocene Epoch would, therefore, require an integrated system of describing, auditing and designating features for conservation. A major benefit of such an approach would be the opportunities for interdisciplinary collaboration between the wide range of researchers interested or involved in studying and conserving the record of anthropogenic activity.
Nuclear receptor gene alteration in human induced pluripotent stem cells with hepatic differentiation propensity
Authors: Itaba Noriko , Wairagu Peninah M. , Aramaki Natsumi , Yasui Toshihiro , Matsumi Yoshiaki , Kono Yohei , Phan Ai N.H. , Otsu Makoto , Kunisada Takahiro , Nakamura Yukio , Okano Hideyuki , Jeong Yangsik , Shiota Goshi
Published: March 2014

Aim

Human induced pluripotent stem (hiPS) cells are an alternative cell source of regenerative medicine for liver disease. Because variations in hepatic differentiation efficacy among hiPS cells exist, it is important to select a hiPS cell line with hepatic differentiation propensity. In addition, nuclear receptors (NR) regulate essential biological processes including differentiation and development. In this study, we identified the hiPS cell line with hepatic differentiation propensity and examined expression levels of 48 NR during this process.

Methods

We screened 28 hiPS cell lines, which are established from various tissues of healthy persons with various reprogramming methods, using a three‐step differentiation method, and examined expression levels of 48 NR by quantitative real‐time polymerase chain reaction during the differentiation process in the selected cells.

Results

hiPS‐RIKEN‐2B and hiPS‐RIKEN‐2F cells have hepatic differentiation propensity. Differentiation propensity towards endoderm was affected by donor origin but not by reprogramming methods or cell type of origins. Expression levels of NR were closely associated with those of hepatic differentiation markers. Furthermore, expression patterns of NR were categorized as five patterns. In particular, seven NR such as chicken ovalbumin upstream promoter transcription factor 1, retinoic acid receptor α, peroxisome proliferator‐activated receptor‐γ, progesterone receptor, photoreceptor cell‐specific nuclear receptor, tailless homolog orphan receptor and glucocorticoid receptor were identified as the genes of which expression gradually goes up with differentiation.

Conclusion

These findings will be useful for not only elucidating mechanisms of hepatic differentiation of hiPS cells but also cell‐based therapy for liver diseases.
Validation and simplification of Fournier's gangrene severity index
Authors: Lin Tsung‐Yen , Ou Chien‐Hui , Tzai Tzong‐Shin , Tong Yat‐Ching , Chang Chien‐Chen , Cheng Hong‐Lin , Yang Wen‐Horng , Lin Yung‐Ming
Published: March 2014

Objectives

To validate the predictive value of Fournier's Gangrene Severity Index in patients with Fournier gangrene and to facilitate patient mortality risk‐stratification by simplifying the Fournier's Gangrene Severity Index.

Methods

From January 1989 to December 2011, 85 male patients with clinically‐documented Fournier's gangrene undergoing intensive treatment and with complete medical records were recruited. The demographic information and nine parameters of Fournier's Gangrene Severity Index were compared between survivors and non‐survivors. The parameters that showed a significant difference between the two groups were selected to generate a simplified scoring index.

Results

Of the 85 patients recruited, 16 patients died of the disease with mortality rate of 18.8%. The Fournier's Gangrene Severity Index score at initial diagnosis was significantly higher in non‐survivors than in survivors. Of the nine parameters of Fournier's Gangrene Severity Index, the scores of serum creatinine level, hematocrit level and serum potassium level were significantly different between the two groups. However, the mean body temperatures, heart rate, respiration rate, white blood cell count, serum sodium and bicarbonate levels were non‐significantly different. Of the 12 patients with chronic kidney disease or end‐stage renal disease, 10 died of severe sepsis. A simplified scoring index including parameters of creatinine, hematocrit and potassium was generated, which provided sensitivity and specificity of 87% and 77% in predicting patient mortality, respectively. The predictive values of this simplified Fournier's Gangrene Severity Index were shown to be non‐inferior to Fournier's Gangrene Severity Index in our patients.

Conclusions

The simplified Fournier's Gangrene Severity Index is easy to use at initial diagnosis, and offers a way to compare outcomes in different clinical populations.
Soft Questions, Hard Answers: Jacob Bernoulli's Probability in Historical Context
Authors: Stigler Stephen
Published: March 2014

On the 300th anniversary of the publication of Jacob Bernoulli's Ars Conjectandi, the book is revisited in historical context and seen in a new light. Bernoulli's announced goal of extending the application of probability from games to civil life was frustrated by the a priori difficulty of specifying equally likely cases. The great approximation theorem Bernoulli proved and suggested could lead to empirical applications was impractical for all but unrealistically large sample sizes, but it was immensely influential in the development of the mathematics of probability.
How much do OECD countries spend on social protection and how redistributive are their tax/benefit systems?
Authors: Adema Willem , Fron Pauline , Ladaique Maxime
Published: March 2014

The global economic crisis has reignited interest in social policy and public spending on different types of social benefits. Public social spending‐to‐GDP ratios are often used to consider the magnitude of welfare systems in international perspective, but such comparisons alone give an incomplete picture of social effort across countries. This article looks at these different factors, before briefly considering the redistributive nature of tax/benefit systems in different member countries of the Organisation for Economic Co‐operation and Development (OECD). The article also considers trends in social spending and compares spending in the late 2000s with the early 1990s when the previous economic crisis played out. The article ends by illustrating the profound effect the recent global economic crisis had on social spending trends across OECD countries.
From pension funds to piggy banks: (Perverse) consequences of the Stability and Growth Pact since the crisis
Authors: Casey Bernard H.
Published: March 2014

As part of their strategy for economic and monetary union, European governments committed themselves to fiscal discipline – particularly by placing limits on annual deficits and on public debt. Subsequently, and as they sought to respond to the “current crisis”, they embraced the view that only if public finances were kept under control would sustainable recovery be possible. Rules of fiscal governance were strengthened. To help them meet these rules, the governments of many member States of the European Union made changes to their pension systems or to funds they had established specifically to pay the costs of population ageing. The intention was not to cut retirement benefits or to improve the efficiency of the relevant pension schemes and institutions. Rather, it was to free up resources immediately. Funded pension schemes and pension funds were treated like “piggy banks” that were raided when times became hard. Moreover, the policies pursued succeeded in meeting their objectives only because the system of national accounts according to which outcomes are judged does not recognize the way in which most of the fiscal gains are matched by future fiscal liabilities.
The Brazilian pension model: The pending agenda
Authors: Matijascic Milko , Kay Stephen J.
Published: March 2014

To achieve national goals defined by the 1988 Brazilian Federal Constitution, cash benefits alone are insufficient in the absence of more robust social services to reduce inequalities and improve social cohesion. The Constitution, albeit of national importance and international significance, has not addressed many institutional and administrative weaknesses in the design of the national pension system. Although coverage has been increased and inequality reduced, these measures are not sufficient. Brazil's ambitions to further develop social policies (and, indeed, to live up to its accorded international status as a social policy leader) may be constrained by an over‐reliance on conditional cash transfers such as those provided under the Bolsa Família programme. Brazil faces a major political‐economy challenge in addressing all these issues because the policy reform process is difficult, and, more importantly, because of the embedded role of vested interests. Moreover, Brazil must tackle these issues in the face of growing fiscal pressures, which could weaken the current political legitimacy of social policy and undermine important recent successes.
Social protection assessment‐based national dialogue exercises: Cambodia, Indonesia, Thailand, Viet Nam
Authors: Schmitt Valérie , Chadwick Rachael
Published: March 2014

Between 2011 and 2013, the International Labour Organization, in collaboration with governments and several United Nations agencies working as part of the Social Protection Floor Initiative, conducted social protection assessment‐based national dialogue (ABND) exercises in Cambodia, Indonesia, Thailand and Viet Nam. The exercises were carried out in order to take stock of existing social protection realities in the respective countries, including social insurance, social assistance and anti‐poverty programmes. These inventories present a comprehensive picture of what elements of national social protection floors (SPFs) are in place, where “holes” in national floors exist, and provide a framework within which to propose recommendations for the further design and implementation of social protection provisions that guarantee at least the SPF to the entire population. This article describes the methodology for conducting ABND exercises, the situational analysis of the SPF in four countries, and the policy recommendations that were formulated for achieving basic health care and income security for children, the working‐age population and the elderly. The results of preliminary calculations of the cost of implementing proposed policy options are also outlined.
The in vivo Anti‐tumor Effect of Human Recombinant Interleukin‐6
Authors: Kitahara Misa , Kishimoto Susumu , Hirano Toshio , Kishimoto Tadamitsu , Okada Masaji
Published: March 2014

Administration of recombinant interleukin‐6 (IL‐6) was found to induce in vivo generation of cytotoxic T lymphocytes (CTL) against syngeneic transplantable erythroleukemia (FBL‐3) in lymph node cells and peritoneal exudate cells (PEC) in C57BL/6 mice. Furthermore, 15 out of 16 C57BL/6 mice injected with 5 × 106 viable FBL‐3 cells survived on day 100 when they were treated with 5 × 104 U of recombinant IL‐6 three times a day on days 1, 2, 3, 5, 7 and 9 after the inoculation of tumor cells (the cure rate was 94%). Cured mice could reject the tumor cells rapidly after the re‐inoculation of a large number of live FBL‐3 cells. In contrast, all normal mice died of tumor development by day 10. In these cured mice, FBL‐3‐specific CD4‐8+ CTL cells were found to be generated in PEC, spleen and lymph node cells by either in vivo or in vitro re‐stimulation with FBL‐3 cells, but lymphokine‐activated killer cells never developed. The results suggested that the anti‐tumor effect of IL‐6 was mediated by in vivo induction of tumor‐specific CTL.
Antitumor Effect of Liposome‐entrapped Adriamycin Administered via the Portal Vein
Authors: Ichino Tatsuo , Yotsuyanagi Toshihisa , Mizuno Isamu , Akamo Yoshimi , Yamamoto Tetsuya , Saito Takaaki , Kurahashi Shingo , Tanimoto Noritaka , Yura Jiro
Published: March 2014

We examined the distribution in tissues and antitumor effect of freeze‐dried liposome‐entrapped adriamycin (Lipo‐ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo‐ADM was determined in rabbits inoculated with VX2 tumor. Repeated injections of free ADM via the portal vein prolonged the life span of tumor‐bearing rabbits. The life span was further prolonged by Lipo‐ADM treatment compared with the control group and the free ADM group. Histological examination revealed that the damage to the liver caused by Lipo‐ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo‐ADM may be more effective in dealing with liver metastases than treatment with free ADM and may be therapeutically useful without toxic side effects.
Epidemiology of gastric cancer in relation to diet and Helicobacter pylori infection
Authors: WONG BENJAMIN CHUN‐YU , LAM SHIU‐KUM
Published: March 2014

Abstract Gastric cancer is the second most common fatal malignancy in the world. In China, gastric cancer is now the second most common malignancy, while in Hong Kong, the mortality rate ranked fourth among all cancers in 1995. Dietary factors in gastric carcinogenesis came mostly from case‐control studies. N‐Nitroso compounds from dietary sources such as preserved, smoked and salted foods were found to be associated with gastric cancer. ß‐Carotene, selenium and α‐tocopherol have been shown in an intervention study to be favourable in the reduction of stomach cancer mortality. Fruits and vegetables showed the most consistent results of inverse association with gastric cancer. Dietary salt intake in preserved or salted foods is also shown to be associated with gastric cancer. Tea drinking, especially green tea, has a protective effect against gastric cancer as shown in some studies. Prospective case‐control studies of the association between Helicobacter pylori infection and the subsequent development of gastric cancer showed that the odds ratio ranged from 2.8 to 6.0. However, results of similar case‐control studies in countries with a high frequency of gastric cancer are controversial. Infection with H. pylori leads to changes in the vitamin C content of gastric juice, reactive oxygen metabolites, epithelial cell proliferation and apoptosis. Recently, CagA‐positive strains were found to be associated with gastric cancer and also duodenal ulcers. The exact role of H. pylori in gastric carcinogenesis is still under investigation. Large‐scale intervention studies are underway to examine dietary supplementation, H. pylori infection and gastric cancer. Helicobacter pylori eradication for gastric cancer prevention is being conducted in China and other parts of the world. In high‐risk areas, for example in China, a combination approach including H. pylori eradication and dietary supplementation may be necessary.
Effects of clarithromycin, omeprazole and leminoprazole on gastric ulcer healing in Helicobacter pylori‐infected rats
Authors: LI T , OKABE S
Published: March 2014

Abstract We examined whether a single inoculation of Helicobacter pylori can colonize the stomachs of ulcerated rats and delay their healing and whether an antibiotic drug and acid pump inhibitors can enhance the ulcer healing in infected rats. Ulcers were produced by a submucosal injection of acetic acid solution into the gastric wall. Helicobacter pylori (ATCC‐43504) was inoculated into rats with and without gastric ulcers. The animals were killed 2, 4, 6, 8 or 10 weeks after the inoculation and the ulcerated area and H. pylori viability were determined. Each test drug and their combination was administered for 1 or 2 weeks after H. pylori inoculation. Helicobacter pylori could not colonize the stomachs of normal rats, but could colonize stomachs with ulcers for 10 weeks at an incidence of >80%. Spontaneous healing of gastric ulcers was delayed by H. pylori infection during these 10 weeks. Daily treatment with clarithromycin significantly and dose‐dependently delayed ulcer healing in infected rats. Both omeprazole and leminoprazole significantly enhanced ulcer healing and inhibited the clarithromycin‐delayed ulcer healing. We conclude that: (i) H. pylori can colonize rat stomachs with ulcers and delay ulcer healing; (ii) clarithromycin delays ulcer healing in H. pylori‐infected rats; and (iii) acid pump inhibitors inhibited the clarithromycin‐delayed ulcer healing.
Cigarette smoking: Effects on P selectin expression and subsequent inflammatory responses in ethanol‐induced gastric mucosal damage
Authors: CHOW JIMMY YC , MA LI , CHO CHI H
Published: March 2014

Abstract Experimental evidence has shown that cigarette smoking potentiates ulcer formation and delays ulcer healing. The exact mechanisms are still not completely defined. We investigated the effects of cigarette smoking on P selectin expression and its actions on neutrophil infiltration and nitric oxide formation in ethanol‐induced gastric mucosal damage. In the present study, rats were exposed to cigarette smoke for three 1 h periods. Cigarette smoke exposure significantly up‐regulated P selectin expression in the gastric mucosa. Cigarette smoke exposure following ethanol challenge substantially potentiated the mucosal damage, which was accompanied with an increase in myeloperoxidase and inducible nitric oxide synthase activities. Anti‐neutrophil serum completely abolished these changes, whereas aminoguanidine produced similar effects without affecting myeloperoxidase activity. Taken together, cigarette smoke exposure can up‐regulate P selectin expression, which facilitates neutrophil rolling, margination and infiltration when challenged with ethanol. These actions activate inducible nitric oxide synthase activity, which may contribute to the potentiating effect of cigarette smoking on ethanol‐induced gastric ulceration in rats.
Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury
Authors: TACHÉ Y , KANEKO H , KAWAKUBO K , KATO K , KIRÁLY Á , YANG H
Published: March 2014

Abstract Activation of medullary thyrotropin‐releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane‐anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin‐sensitive splanchnic afferents leading to calcitonin gene‐related peptide (CGRP)‐ and nitric oxide (NO)‐dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal‐dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal‐dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non‐adrenergic, non‐cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal‐dependent mechanisms which increase the resistance of the gastric mucosa to injury.
Effectiveness and cost‐effectiveness of colorectal cancer screening: Selecting the ideal strategy
Authors: BOND JOHN H
Published: March 2014

Abstract Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence‐based guidelines recommend that the average‐risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost‐effective in a high‐risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.
Hepatitis C and hepatocellular carcinoma
Authors: OKUDA KUNIO
Published: March 2014

Abstract Hepatitis C virus (HCV) infection is aetiologically very closely associated with hepatocellular carcinoma (HCC). World‐wide, hepatitis B virus infection is the predominant aetiological factor in developing countries, whereas in industrialized countries, HCV has a far more important role in hepatocarcinogenesis. The varying weights of the aetiological role of HCV infection are compared among countries. The speed of progression of chronic hepatitis C to cirrhosis, thenceforth to HCC, and certain discrepancies between an American study and the Japanese experience are described. The reason for the recent surge of HCV infection and subsequent increase in the incidence of HCC is also discussed. The genetic mechanism of HCV‐induced hepatocarcinogenesis is still poorly understood.
Liver transplantation in Asia: Problems and practice
Authors: FAN ST
Published: March 2014

Abstract Liver transplantation in Asia has been difficult to establish due to: a reluctance in Asians to donate organs; a lack of financial support; and the predominance of hepatitis B in the population, which effectively reduces the number of cadaveric organs. To overcome the problem of organ shortage, living‐related liver transplantation for paediatric patients was rapidly established initially at Kyoto University, Japan, and then in several centres in Asia. Living‐related liver transplantation was extended to adults using the left lobe in 1994 and using the right lobe in 1996. Up to May 1998, 785 liver transplantations had been performed in major centres in Asia with a patient survival rate approaching 80%. To overcome the problem of hepatitis B viral infection, lamivudine is now used peri‐operatively. Lamivudine is shown to be very effective in preventing graft reinfection. Of the 15 patients who received lamivudine and liver transplantation at Queen Mary Hospital, hepatitis B surface antigen (HBsAg) disappeared in 11 patients and hepatitis B virus DNA was not detectable in any of them. Two patients had a reappearance of HBsAg after an initial loss, but their liver grafts were not affected by hepatitis. Compared with hepatitis B immunoglobulin, lamivudine is definitely cheaper and more convenient. In conclusion, even though there are major obstacles to liver transplantation in Asia, steady progress is being made. Hopefully, when the number of cadaveric grafts increases in future, an increasing number of patients can benefit.
New treatment for hepatocellular carcinoma
Authors: JOHNSON PHILIP J
Published: March 2014

Abstract Although the incidence of hepatocellular carcinoma (HCC) is likely to start falling in many countries following mass vaccination programmes, large numbers of new cases are likely to be seen for many years to come. For the majority of patients, only palliative treatments can be offered. Systemic chemotherapy does not improve survival. Locoregional therapy is widely used and certainly results in a consistent decrease in tumour size, but clear evidence of any improvement in overall survival remains elusive. We have recently described the application of selective internal radiotherapy using 90yttrium microspheres. Although response rates by conventional radiological criteria were only modest, several initially inoperable cases became operable and subsequent resection revealed complete pathological remission in some. The resection became possible, not only because of tumour shrinkage, but also because of hypertrophy of the non‐tumorous liver. To date, only a small number, probably less than 15% of patients with HCC will be suitable for an attempt at surgical resection and recurrence will occur in more than half of these. We have recently shown that postoperative intra‐arterial administration of Lipiodol I131 may significantly decrease this recurrence rate.
Severe Sepsis following Percutaneous or Endoscopic Procedures for Urinary Tract Stones
Authors: O'KEEFFE N. K. , MORTIMER A. J. , SAMBROOK P. A. , RAO P. N.
Published: March 2014

Summary— Nine cases of severe sepsis following percutaneous or endoscopic procedures for upper urinary tract stones are reported. The mortality rate was 66%. Despite the fact that approximately 700 procedures were carried out in males and females in roughly equal proportions, a striking but inexplicable feature was that all 9 patients in the study group were female. Severe systemic sepsis has a high mortality rate and any procedure that may put patients at risk of this complication should not be undertaken lightly (and certainly not as an out‐patient procedure). Recovery is possible with a high index of suspicion, early intervention and intensive treatment.
The Ureter in vitro: Normal Motility and Response to Urinary Pathogens
Authors: LENNON G. M. , RYAN P. C. , FITZPATRICK J. M.
Published: March 2014

Summary— The effects of bacteria on in vitro ureteric contractility were studied, using a model which allowed selective exposure of organisms to the ureteric mucosa and smooth muscle, respectively. A cannula attached to a pressure transducer was ligated into the proximal lumen of 2.5‐cm segments of canine ureter. The distal ureter was ligated to form a closed pressure monitored system, and the segment suspended in a 20‐ml organ bath containing Krebs Henseleit buffer at physiological pH and temperature. Following onset of spontaneous activity, broths of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus were added to either the buffer solution or ureteric lumen in doses of > 106 organisms/ml. Experiments were repeated using heat‐killed organisms, bacterial filtrates and E. coli endotoxin. Ureteric contractility was stimulated by organisms added to the buffer medium, but reversibly inhibited by bacteria placed in the ureteric lumen. Heat‐killed organisms, endotoxin and live filtrates had no effect on normal motility when exposed to either the ureteric mucosa or muscularis respectively. These findings reflect the conflicting changes in ureteric motility seen in vivo when bacteria are administered systemically or directly into the ureteric lumen.
Ureteric Peristalsis Studies in Loin Pain and Haematuria Syndrome: Another Diagnostic Disappointment
Authors: WOOLFSON R. G. , LEWIS C. A. , HILL P. D. , HILSON A. J. W. , NEILD G. H.
Published: March 2014

Summary— Although not a cause of progressive renal damage, loin pain and haematuria syndrome is nevertheless associated with significant morbidity. The management of pain often presents a formidable problem to urologists, physicians and general practitioners. An earlier study noted holdup of urine in the renal pelvis and implicated this in the pathogenesis of pain. In this study we have failed to demonstrate an excess incidence of disordered urinary peristalsis in loin pain and haematuria syndrome.
Search for Mycobacteria in Interstitial Cystitis Using Mycobacteria‐specific DNA Probes with Signal Amplication by Polymerase Chain Reaction
Authors: HAMPSON S. J. , CHRISTMAS T. J. , MOSS M. T.
Published: March 2014

Summary— The aetiology of interstitial cystitis is not known. Various infective agents have been postulated and although recognised as perpetrators of chronic inflammatory conditions, mycobacteria have never been satisfactorily excluded from interstitial cystitis. If present in interstitial cystitis tissue, mycobacteria exist either in very small numbers or in forms which contemporary staining techniques fail to recognise. We used a polymerase chain reaction with mycobacteria‐specific DNA probes and found no evidence of mycobacterial involvement in 8 cases of proven interstitial cystitis.
Transurethral Resection for a Large Prostate—Is it Safe?
Authors: AGARWAL M. , PALMER J. H. , MUFTI G. R.
Published: March 2014

Summary— A retrospective self‐audit exercise was undertaken on 47 men who underwent transurethral resection of the prostate and in whom the resected weight was 80 g or more. The operative mortality and morbidity rates were 6 and 55% respectively, being highest in the “very old and unfit” group (22 and 88%). The complication rate increased if the resected prostatic weight was 100 g or more, or if the resection time exceeded 75 min. It was concluded that careful selection of patients is necessary before undertaking TUR for a large gland.
Evolving Experience with Radical Prostatectomy
Authors: BRASLIS K. G. , BOWSHER W. G. , JOYCE G. , PETERS J. , COSTELLO A. J.
Published: March 2014

Summary— Thirty‐six radical prostatectomies were performed over an 8‐year period; 25 suitable patients (70%) presented with symptoms of bladder outflow obstruction. In 15 cases (44%), initial digital rectal examination was not indicative of malignancy. The primary tumour was understaged pre‐operatively in 17 patients (48%). In 14 cases (41%) the pre‐operative biopsy grade was different from the grade assigned to the tumour following radical prostatectomy. Radical prostatectomy is being performed with increasing frequency: trends in morbidity have been identified.
Electromyography of Cavernous Smooth Muscle during Flaccidity: Evaluation of Technique and Normal Values
Authors: MERCKX L. A. , DE BRUYNE R. M. , KEUPPENS F. I.
Published: March 2014

Summary— Objective evaluation of the penile innervation in impotent patients is mostly restricted to examination of the somatic pudendal pathways. These tests provide little information on the pelvic‐cavernous autonomic innervation of the corporeal bodies. Electromyography of the flaccid penile smooth muscle is a reproducible and non‐invasive method of evaluating these autonomic pathways and the status of intrinsic smooth muscle. Examination techniques and normal values have been studied in 15 young and potent volunteers. Recordings in 13 patients with neuropathology and 57 impotent patients are discussed.
Intravesical Ureteric Plication and Reimplantation for Megaureters in Children
Authors: ÖZEN H. A. , TEKGÜL S. , ERKAN I. , BAKKALOĞLU M.
Published: March 2014

Summary— Historically, megaureters have always been a surgical dilemma for paediatric urologists. However, the evolution of modern diagnostic and surgical methods such as tailoring, folding and plication have made it possible to ensure successful correction in most patients.

We report 17 megaureters (11 refluxing and 6 obstructing) in 11 children who were treated with intravesical plication and the transtrigonal advancement technique between January 1986 and April 1991. Results were excellent in 11 ureters and satisfactory in 4. In one ureter additional surgery was needed because of obstruction at the implantation site and in another ureter reflux persisted.

Intravesical plication and reimplantation is a good alternative procedure for grossly dilated ureters owing to its low morbidity and high success rate.
BEHAVIORAL THERAPY FOR OVERACTIVE BLADDER
Authors: PAYNE CHRISTOPHER K.
Published: March 2014

What is behavioral therapy? On the one hand there is no consensus in the literature as to the definition of the treatment or the optimal mode of delivery. On the other hand, it is possibly the “best” single treatment for urinary incontinence when viewed from a risk:benefit analysis. There is general agreement that within this framework wide variations exist in intensity of treatment, expertise required to deliver the treatment, and the subsequent cost of therapy. A definition of behavioral therapy should include at least the following techniques: first, education and explanation of normal lower urinary tract function; second, micturition charts and diaries; and finally, timed voiding/bladder training regimens. All of the behavioral methods are demonstrably effective, with improvement rates in incontinence episodes uniformly in excess of 50%. Our challenge is to define the critical parts of behavioral therapy and develop algorithms that can be delivered to the incontinent population in the most cost‐effective manner.
ELECTRICAL STIMULATION IN OVERACTIVE BLADDER
Authors: BRUBAKER LINDA
Published: March 2014

Electrical stimulation is an effective and well‐tolerated treatment for overactive bladder. Initial work in animals indicated the potential of this treatment, and early clinical experience in Europe further supported its likely efficacy. Although the mechanism of action of electrical stimulation remains unproven in humans, it is believed to be a neuromodulating therapy which affects the neural signaling that controls continence. There is also strong evidence that electrical stimulation affects striated muscle. The therapy can cause hypertrophy of skeletal muscle fibers, possibly by the recruitment of faster‐conducting motor units, which would not normally be recruited during voluntary efforts. In addition, electrical stimulation can alter the expression of myosin isoforms, favoring a conversion to type I muscle. Despite our incomplete understanding of the mechanism of action of electrical stimulation, clinical devices have been developed quickly. Case series have been reported throughout Europe. These were followed by controlled clinical trials in the United States. There is good evidence that the use of vaginal electrical stimulators can reduce the occurrence of symptoms of overactive bladder in about half of the patients treated. Multiple uses of nonimplanted stimulation, including thigh stimulation, anal stimulation, and direct pelvic muscle stimulation, have been reported. In these trials, it is common for objective findings to be poorly correlated with subjective reports of improvements or cure. Patients frequently report that the urge‐to‐leak time improves, but this is difficult to measure objectively. The use of nonimplanted devices is effective and well tolerated, and should precede the use of implanted devices. A direct comparison with other effective methods of treatment for overactive bladder is warranted.
New methods of bladder augmentation
Authors: ATALA A.
Published: March 2014

Gastrointestinal segments are commonly used for bladder replacement or repair. However, when gastrointestinal tissue is in contact with the urinary tract, several complications may ensue. Recent surgical approaches have relied on native urological tissue for reconstruction. These are based on sound surgical principles, allowing for the exclusion of tissue that is not urological. De‐epithelialized bowel segments, either alone or over native urothelium, have also been used. An experimental system of progressive dilatation for ureters and bladders has been proposed. This appears promising, although it has yet to be attempted clinically. There has been a resurgence of interest in the use of acellular collagen‐based matrices as scaffolds for bladder regeneration; experimental work is currently underway. Recently, functional bladder tissue has been engineered using selective cell transplantation. This technique uses autologous cells, so avoiding rejection. Tissue is obtained from the host, the cells then dissociated and expanded in vitro, re‐attached to a matrix and implanted into the same host. Clinical trials are currently being arranged. Even though the use of bowel for bladder tissue replacement was first proposed over 100 years ago, it remains the gold standard, despite its associated problems. It is evident that urothelial‐urothelial anastomoses are preferable functionally. Experience is currently being gained with the recent clinical and experimental approaches to augmentation cystoplasty. It is hoped that this will result in more technologies and methods for bladder augmentation.