bluuebunny/crossref_metadata_2025 huggingface dataset:
Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats
Authors: Ranganathan Natarajan , Patel Beena , Ranganathan Pari , Marczely Joseph , Dheer Rahul , Chordia Tushar , Dunn Stephen R. , Friedman Eli A.
Published: October 2005

The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo-controlled pilot study, using 5/6thnephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A) Control, (B) Placebo (casein-based diet without probiotics), (C)Bacillus pasteurii, (D) Sporolac®, (E) Kibow cocktail, (F) CHR Hansen Cocktail, and (G) ECONORMTM. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine respectively), body weight and bacterial counts (feces) were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1) decreased blood concentrations of uremic toxins, (2) altered renal function, and (3) prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure.
Ovarian Abnormalities in the Staggerer Mutant Mouse
Authors: Guastavino Jean-Marie , Boufares Salima , Crusio Wim E.
Published: October 2005

Disturbances in several reproductive functions of the staggerer cerebellar mutant mouse have been observed. In this study, reproductive efficiency ofstaggerermice was compared to normal mice by recording the number of pups produced and the number of oocytes occurring. It was found thatstaggerermothers produced smaller litters than controls and the number of oocytes produced in their ovaries was reduced by thestaggerermutation. These results indicate a pleiotropic effect on fertility of the Rorasggene underlying the cerebellar abnormalities of thestaggerermutant.
Cultural Aspects of Suicide
Authors: Maharajh Hari D. , Abdool Petal S.
Published: October 2005

Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.
Suicide Behavior in Persons with Intellectual Disability
Authors: Merrick Joav , Merrick Efrat , Lunsky Yona , Kandel Isack
Published: October 2005

Suicide is today in the Western world one of the leading causes of death and most people have had suicidal ideation at some time during their life. In the population of persons with intellectual disability some researchers have thought that impaired intellectual capacity could act as a buffer to suicidal behavior, but the fact is that the few studies conducted in that population contest this assumption and showed that the characteristics of suicidality in this population are very similar to persons without intellectual disability. This paper reviews the studies conducted and describe the symptomatology in this population. Professionals working with this population should therefore be aware of and assess for this behavior. Sadness or depression are symptoms that could indicate later suicidal behavior.
Suicide from a Holistic Point of View
Authors: Ventegodt Søren , Merrick Joav
Published: October 2005

Suicide has been honoured and respected in the eastern culture, especially in Japan with the famous tradition of Hara-kiri, or seppuku, while in most western societies suicide has been seen negatively and many contemporary physicians tend to consider suicide the most self-destructive and evil thing a human being can do and something that should be avoided at all cost. Religions also have different viewpoints on suicide, but from a philosophical point of view we believe that considering the choice of life and dead to be extremely relevant for a good living. The choice of life and dead is real, since responsibility for life is necessary in order to live life and even the best physician cannot keep a patient alive, who deep inside wants to die. In this chapter, we present parts of a story of a young girl who had experienced child sexual abuse. In holistic existential therapy, it is our experience, when the patient is well supported in the confrontation of the fundamental questions related to assuming responsibility for the coherence, that this confrontation will almost always lead to a big YES to life. Without confronting the fundamental question of “to be or not to be”, life can never be chosen 100% and thus never be lived fully.
Incontinence and Erectile Dysfunction Following Radical Prostatectomy: A Review
Authors: Alivizatos Gerasimos , Skolarikos Andreas
Published: October 2005

Radical prostatectomy remains the treatment of choice for localized prostate cancer in age-appropriate and health-appropriate men. Although cancer control is the most important aspect of a radical prostatectomy, minimization of postoperative morbidity, especially urinary incontinence and erectile dysfunction, is becoming a greater concern. We reviewed recent data available on Medline regarding the incidence, pathophysiology, evaluation, and treatment of incontinence and sexual dysfunction after radical prostatectomy. Health-related quality of life issues have been specifically addressed. Although low incidences of incontinence and erectile dysfunction after radical prostatectomy have been reported in the hands of experienced surgeons, the literature review revealed a great variety, with incontinence rates ranging from 0.3–65.6% and potency rates ranging from 11–87%. Several factors contribute to this wide difference, the most important being the application of a meticulous surgical technique. General and cancer-specific health-related quality of life is not being affected after radical prostatectomy. The incidence of incontinence and erectile dysfunction is higher after radical prostatectomy when compared to the incidence observed when other therapies for localized prostate cancer are applied. However, the majority of the patients undergoing radical prostatectomy would vote for the operation again. Today, avoidance of major complications after radical prostatectomy depends mostly on a high-quality surgical technique. When incontinence or erectile dysfunction persists after radical prostatectomy, the majority of the treated patients can be managed effectively by various methods.
The Relationship of Work Stress and Family Stress to the Self‐Rated Health of Women Employed in the Industrial Sector in Korea
Authors: Kim Gwang Suk , Cho Won Jung , Lee Chung Yul , Marion Lucy N. , Kim Mi Ja
Published: October 2005

Abstract 
Objective:
To identify the relationship of work stress and family stress to the health of women in Korea. Design: Cross‐sectional study. Sample: Three hundred and thirty‐one married women working in 14 manufacturing companies in Korea. Methods: Subjects responded to a questionnaire that included items on work stress, family stress, social support, and general characteristics. Perceived health status (PHS) was assessed with the Short Form‐36. Results: There was a significant positive relationship between social support and PHS, but significant negative relationships were found between PHS and work stress as well as family stress. Hierarchical multiple regression analysis explained the health status of married working women by four categories: personal, work related, family related, and social support, and accounted for 45.4% of the variance. When family‐related factors were added to the model, the power of explanation was increased by 17.9% compared with the explained variance. Family stress was a major variable not only for explaining the variance but also for correlating with health status. Conclusions: Both work stress and family stress should be considered together when addressing the health of working women in the industrial sector in Korea.
The Experience of Quarantine for Individuals Affected by SARS in Toronto
Authors: Cava Maureen A. , Fay Krissa E. , Beanlands Heather J. , McCay Elizabeth A. , Wignall Rouleen
Published: October 2005

Abstract 
Objective:
The purpose of this study was to explore the experience of home quarantine during the severe acute respiratory syndrome (SARS) outbreak in Toronto in 2003. Design: Qualitative descriptive design. Sample: Stratified random sampling techniques were used to generate a list of potential participants, who varied in terms of gender and closeness of exposure to someone with suspected SARS (contact level). Twenty‐one individuals participated in the study. Measurements: All interviews were audiotaped and followed a semistructured interview guide. Participants were invited to describe their experience of quarantine in detail including their advice for Public Health. Results: The experience followed a trajectory of stages beginning before quarantine and ending after quarantine. Despite individual differences, common themes of uncertainty, isolation, and coping intersected the data. Conclusions: Public Health has a dual role of monitoring compliance and providing support to people in quarantine. This study has implications for public health policy and practice in planning for future public health emergencies in terms of the information and the resources required to mount an effective response.
Evaluation of a Community‐Based Exercise Program for Elderly Korean Immigrants
Authors: Sin Mo‐Kyung , Belza Basia , LoGerfo James , Cunningham Susanna
Published: October 2005

Abstract 
Objective:
To evaluate feasibility and effectiveness of a modified exercise program for elderly Korean immigrants (EKIs). Design and sample: Intervention study with EKI residents of a senior house (n = 13, age range 67–86 years, mean age 77 years), recruited through posted fliers and with help from a Korean social worker. Intervention: A Korean–American instructor taught a modified version of an evidence‐based exercise program 3 times weekly, 50 min per session, for 12 weeks. Program was evaluated with the Quality Health Outcomes Model. System and client characteristics were taken into consideration because elderly Koreans have their own values and beliefs, which influence their health management behaviors. Evaluation measures included exercise adherence, preintervention and postintervention health outcomes, and satisfaction with the exercise program. Group discussion was used to evaluate satisfaction with the exercise program. Results: Participants showed improved health outcomes on muscle strength, agility/balance, and blood pressure after the exercise program. All participants were satisfied with the exercise program, and participation rates were good (nine participants attended ≥ 80% of classes). Conclusions: The exercise program was feasible for this sample and should be evaluated in a larger population of EKIs and in populations of other ethnic minorities.
The Volunteer Potential of Inactive Nurses for Disaster Preparedness
Authors: Fothergill Alice , Palumbo Mary Val , Rambur Betty , Reinier Kyndaron , McIntosh Barbara
Published: October 2005

Abstract 
Objectives:
Inactive nurses' interest in volunteering for emergency preparedness was examined. Methods: A mail survey was sent to the entire Vermont Board of Nursing list of in‐state inactive and lapsed registered nurses (n = 3,682). A high rate of undeliverable surveys (60%) was found and 611 surveys were returned for a 20% response rate. Results: Twenty‐seven percent of the respondents were interested in volunteering. Those interested in participating in volunteer work as part of a national homeland security effort were significantly more likely to (a) be younger in age (p < 0.0001); (b) identify themselves as “being a nurse” (p = 0.001); (c) be employed versus retired (p = 0.002); and (d) be currently volunteers (p = 0.001). Conclusions: Because 33% of the nation's nurses are over age 50, inactive nurses offer a potentially large pool of volunteers for emergency preparedness training and response in the years to come.
A Naturalistic Test of Peplau's Theory in Home Visiting
Authors: McNaughton Diane B.
Published: October 2005

Abstract  Nurse‐client relationships have been considered the foundation of successful home‐visiting programs for vulnerable families (Gomby, Culross, & Behrman, 1999; McNaughton, 2000; Olds & Kitzman, 1990). Even though nurse‐client relationships are important when working with multiproblem families, relationship theory has not been used to guide interventions in home visiting. Identification of a fitting theory could provide direction for tailoring interventions to families at a “dose” individualized to meet their needs.

This article reports a small study that tested the applicability of Peplau's theory of interpersonal relations in nursing (Peplau, 1952/1991) in the context of home visiting. Five prenatal clients and public health nurses participated in the study. Home visits were observed and audio‐recorded beginning with the first prenatal home visit and ending in the early postpartum period. Audiotapes were transcribed and analyzed using a start list of codes (Miles & Huberman, 1994) based on Peplau's theory. Changes in the percentage of interaction assigned to the relationship phases along with a rating from the Relationship Form (Forchuk & Brown, 1989) were compared over time to determine whether relationships progressed as predicted by Peplau. Findings of this study supported Peplau's theory. Implications for nursing practice and research are discussed.
Doris Wagner Ferguson, Still Waters Run Deep: An Oral History
Authors: Knollmueller Ruth N.
Published: October 2005

Abstract  Doris Wagner Ferguson, MS, RN, FAAN, an original member of the journal of Public Health Nursing editorial board, is now retired in Oklahoma after a 50‐year career in public health nursing. She has been a staff nurse, an administrator, and an educator in several states and, in each instance, was instrumental in effecting change and improvement for the practice of her specialty. Her story informs us of earlier struggles and challenges, which we may take for granted today. Those of us currently working in public health nursing acknowledge that we stand on the shoulders of nurses like Doris Wagner Ferguson.
Invasive human pancreatic carcinoma cells adhere to endothelial tri‐cellular corners and increase endothelial permeability
Authors: Nakai Kei , Tanaka Toshiyuki , Murai Toshiyuki , Ohguro Nobuyuki , Tano Yasuo , Miyasaka Masayuki
Published: October 2005

Although adhesive interactions between metastasizing cancer cells and vascular endothelial cells are critical in hematogenous metastasis, the early molecular events of the cancer–endothelial interaction remain largely obscure. Here we investigated the functional impact of cancer cells on endothelial permeability. We examined the binding of human pancreatic carcinoma cells MIA PaCa‐2, PANC‐1 and PSN‐1 to a human umbilical vein endothelial cell (HUVEC) monolayer and the subsequent changes in the transendothelial electronic resistance (TEER) of the HUVEC. We found that MIA PaCa‐2 and PANC‐1 cells preferentially bound to the tri‐cellular corners of HUVEC and induced a rapid and irreversible reduction of TEER. The reduction of HUVEC TEER was associated with the focal disengagement of endothelial junctional adhesion molecules VE‐cadherin and CD31. Blocking antibodies to integrin β1, CD44, or CD9 affected neither the MIA PaCa‐2 binding to HUVEC nor the reduction of TEER. Specific inhibitors for metalloproteinases, tyrosine‐kinases and lipoxigenases, and a neutralizing anti‐vascular endothelial growth factor antibody failed to affect the MIA PaCa‐2‐induced reduction of HUVEC TEER, whereas treatment of the cells with paraformaldehyde or cytochalasin B abrogated the TEER reduction. These findings indicate that the MIA PaCa‐2 cells bind selectively to endothelial tri‐cellular corners, triggering a reduction of HUVEC TEER, which requires the active metabolism and intact actin cytoskeleton of the carcinoma cells, and is apparently unrelated to previously described cell adhesion and soluble factor pathways. Our data indicate a novel cell‐contact‐dependent mechanism for the cancer cell‐mediated breakdown of endothelial barrier functions, which may be important in hematogenous cancer metastasis. (Cancer Sci 2005; 96: 766–773)
The ALK‐5 inhibitor A‐83‐01 inhibits Smad signaling and epithelial‐to‐mesenchymal transition by transforming growth factor‐β
Authors: Tojo Masayoshi , Hamashima Yoshio , Hanyu Aki , Kajimoto Tetsuya , Saitoh Masao , Miyazono Kohei , Node Manabu , Imamura Takeshi
Published: October 2005

Transforming growth factor (TGF)‐β signaling facilitates tumor growth and metastasis in advanced cancer. Use of inhibitors of TGF‐β signaling may thus be a novel strategy for the treatment of patients with such cancer. In this study, we synthesized and characterized a small molecule inhibitor, A‐83‐01, which is structurally similar to previously reported ALK‐5 inhibitors developed by Sawyer et al. (2003) and blocks signaling of type I serine/threonine kinase receptors for cytokines of the TGF‐β superfamily (known as activin receptor‐like kinases; ALKs). Using a TGF‐β‐responsive reporter construct in mammalian cells, we found that A‐83‐01 inhibited the transcriptional activity induced by TGF‐β type I receptor ALK‐5 and that by activin type IB receptor ALK‐4 and nodal type I receptor ALK‐7, the kinase domains of which are structurally highly related to those of ALK‐5. A‐83‐01 was found to be more potent in the inhibition of ALK5 than a previously described ALK‐5 inhibitor, SB‐431542, and also to prevent phosphorylation of Smad2/3 and the growth inhibition induced by TGF‐β. In contrast, A‐83‐01 had little or no effect on bone morphogenetic protein type I receptors, p38 mitogen‐activated protein kinase, or extracellular regulated kinase. Consistent with these findings, A‐83‐01 inhibited the epithelial‐to‐mesenchymal transition induced by TGF‐β, suggesting that A‐83–01 and related molecules may be useful for preventing the progression of advanced cancers. (Cancer Sci 2005; 96: 791–800)
Serum level of soluble CD30 correlates with the aggressiveness of adult T‐cell leukemia/lymphoma
Authors: Nishioka Chie , Takemoto Shigeki , Kataoka Sayo , Yamanaka Shigeo , Moriki Toshiaki , Shoda Momoko , Watanabe Toshiki , Taguchi Hirokuni
Published: October 2005

Adult T‐cell leukemia/lymphoma (ATL) is a highly aggressive disease with poor prognosis. CD30+ cells are frequently observed in lymph node cells and peripheral blood mononuclear cells of ATL patients. In order to elicit the role of CD30+ cells in ATL development, we investigated expression of the membrane type of CD30 (mCD30) and the soluble form of CD30 (sCD30) on ATL cells. Both mCD30 and sCD30 are expressed on various numbers of ATL cells in vivo as well as cell lines such as MT‐2, L540 and Karpas 299. The level of serum sCD30 in each clinical stage showed an elevated level in patients with acute type (mean ± standard error; 545.2 ± 18.6 U/mL) rather than with lymphoma type ATL (327.62 ± 94.85 U/mL). In four patients whose sera were stored and examined longitudinally, the levels decreased following the response to chemotherapy but not in patients with chemotherapy resistance. Thus, our results imply that sCD30 levels may be another useful marker for the activity and aggressiveness of ATL. (Cancer Sci 2005; 96: 810–815)
Involvement of mitochondrial aggregation in arsenic trioxide (As2O3)‐induced apoptosis in human glioblastoma cells
Authors: Haga Naomi , Fujita Naoya , Tsuruo Takashi
Published: October 2005

Arsenic trioxide (As2O3) is effective against acute promyelocytic leukemia and has potential as a novel treatment against malignant solid tumors. As2O3 induces differentiation and inhibits growth. It also causes mitochondrial damage mediated by the production of reactive oxygen species (ROS) and the dissipation of mitochondrial transmembrane potential (ΔΨm), leading to apoptosis. Mitochondria might be the key target of antitumor activity by As2O3; however, its mechanisms have not been completely elucidated. Using two human glioblastoma cell lines, A172 and T98G, we found that As2O3 induced apoptosis in A172 cells but not in T98G cells. As2O3‐induced ROS production was observed in both cell lines; however, the dissipation of ΔΨm, Bax oligomerization and caspase activation occurred only in As2O3‐sensitive A172 cells. To determine the mechanisms of As2O3‐induced apoptosis after ROS generation, we examined the change of mitochondrial morphology. As we reported previously, mitochondrial aggregation occurs before cytochrome c release during apoptosis, thus playing a role in cell death progression. We observed mitochondrial aggregation in As2O3‐sensitive A172 cells but not in T98G cells treated with As2O3. Using laser scanning cytometry, we quantitatively confirmed the results, which indicate that mitochondrial aggregation plays an important role in regulating sensitivity to As2O3‐induced apoptosis. We propose a sequential process involving ROS generation, mitochondrial aggregation, Bax oligomerization and ΔΨm dissipation, and caspase activation during As2O3‐induced apoptosis. (Cancer Sci 2005; 96: 825–833)
Review article: adipocytokines and insulin resistance
Authors: VETTOR R. , MILAN G. , ROSSATO M. , FEDERSPIL G.
Published: October 2005

Insulin resistance has been implicated as one possible factor that links visceral obesity to unfavourable metabolic and cardiovascular consequences. However, the mechanism whereby adipose tissue causes alterations in insulin action remains unclear. White adipose tissue is secreting several hormones, particularly leptin and adiponectin, and a variety of other protein signals: the adipocytokines. They include proteins involved in the regulation of energy balance, lipid and glucose metabolism as well as angiogenesis, vascular and blood pressure regulation. Visceral obesity and inflammation within white adipose tissue may be a crucial step contributing to the emergence of insulin resistance, type 2 diabetes and atherosclerosis. A growing list of adipocytokines involved in inflammation (IL‐1β, IL‐6, IL‐8, IL‐10, TNF‐α, TGF‐β,) and the acute‐phase response (serum amyloid A, PAI‐1) have been found to be increased in the metabolic syndrome. It is, however, unclear as to the extent adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and how they may affect the insulin‐dependent tissues. This review describes the role of the currently known adipocytokines and hormones released by adipose tissue in generating the insulin resistance state and the chronic inflammatory profile which frequently goes together with visceral obesity.
Review article: the metabolic syndrome – a chronic cardiovascular inflammatory condition
Authors: ZAMBON A. , PAULETTO P. , CREPALDI G.
Published: October 2005

The atherosclerotic process is regulated by inflammatory mechanisms, which also appear to be involved in the modulation of insulin‐resistance, a key player in the pathogenesis of the metabolic syndrome (MS). The interaction between components of the clinical phenotype of the MS with its biological phenotype (insulin resistance, dyslipidaemia, etc.) contributes to the development of a pro‐inflammatory state characterized by an increased oxidative stress (i.e. oxidized lipoproteins) and a chronic, subclinical vascular inflammation, as also suggested by the increased C reactive protein (CRP) concentration found in patients with MS. The subclinical inflammatory state peculiar of the MS modulates the atherosclerotic process at different stages, resulting in: (i) endothelial dysfunction and increased expression of endothelial adhesion molecules; (ii) an enhanced recruitment of monocytes within the arterial wall, in the early stages of the atherosclerotic process; leading to (iii) the formation of an unstable atherosclerotic plaque, rich in inflammatory cells, which is the culprit lesion in the vast majority of both coronary and cerebrovascular events observed in with MS.
Review article: type 2 diabetes and chronic liver disease in the Verona diabetes study
Authors: TROMBETTA M. , SPIAZZI G. , ZOPPINI G. , MUGGEO M.
Published: October 2005

Non‐alcoholic liver steatosis is associated with metabolic syndrome and type 2 diabetes. The prevalence of this condition in type 2 diabetes is estimated to be between 28 and 55%. Non‐alcoholic liver steatosis is not a benign disease because of its potential progression to liver fibrosis, cirrhosis and cancer. The Verona diabetes study, a population‐based observational study, on 7148 type 2 diabetic patients after 5 years of follow‐up has reported an increased risk of death from gastrointestinal diseases, particularly from chronic liver cirrhosis. Moreover, in the same population after 10 years of follow‐up a higher risk of mortality from liver cancer was observed and this risk increased significantly in obese patients (body mass index >30 kg/m2). Of note is that obese diabetic patients suffer an even higher prevalence of non‐alcoholic liver steatosis. In conclusion, the Verona diabetes study showed an increased risk of mortality from liver cirrhosis and liver cancer in type 2 diabetic patients. Diverse pathophysiological mechanisms can be responsible, i.e. higher alcohol consumption, hepatitis and others but, considering the high prevalence of non‐alcoholic liver steatosis in these patients, it is plausible to hypothesize that non‐alcoholic liver steatosis may play a significant role in predisposing the liver of diabetics to chronic diseases.
Review article: hyperlipidaemia and cardiovascular risk
Authors: BERTOLOTTI M. , MAURANTONIO M. , GABBI C. , ANZIVINO C. , CARULLI N.
Published: October 2005

Hyperlipidaemia represents a determinant for the development of atherosclerosis and an important risk factor for cardiovascular disease, particularly in the context of the insulin resistance syndrome. This is characterized by alterations in the profile of plasma lipoprotein including high triglyceride levels, low high‐density lipoprotein cholesterol concentrations and the appearance of qualitatively modified, small‐dense low‐density lipoproteins. Many charts and algorithms have been developed to estimate the entity of coronary and cardiovascular risk as related to dyslipidaemia, on the basis of additional individual risk factors and conditions: most include age and gender, smoking status, hypertension and diabetes. They should preferably be utilized in consistent patient populations, in terms of geographical areas and general risk profile. Pharmacological treatment of dyslipidaemia, in particular with statin drugs, was shown to greatly improve cardiovascular morbidity and mortality. A body of evidence also underlines the need for a multidisciplinary approach, integrating non‐pharmacological lifestyle and diet interventions, as well as treatment of concomitant diseases (hypertension and diabetes).
Review article: the pathogenesis of fibrosis in non‐alcoholic steatohepatitis
Authors: MARRA F. , ALEFFI S. , BERTOLANI C. , PETRAI I. , VIZZUTTI F.
Published: October 2005

Non‐alcoholic steatohepatitis has been recognized as a significant cause of end‐stage liver disease and hepatic decompensation. Despite the growing interest in this condition, the molecular mechanisms underlying the development of fibrosis in this setting are only partially understood. In this article, the cellular and molecular basis of fibrosis in chronic liver disease are briefly outlined. In addition, mechanisms specifically operating in the context of fatty liver and steatohepatitis are examined, including: insulin resistance, oxidative stress, and inflammation. Finally, recent developments indicating the possible contribution of cytokines derived from adipose tissue (adipokines) to liver fibrosis is discussed.
Review article: an unexpected virus–host interaction – the hepatitis C virus‐diabetes link
Authors: RATZIU V. , HEURTIER A. , BONYHAY L. , POYNARD T. , GIRAL P.
Published: October 2005

There is now consistent epidemiological evidence for an association between chronic hepatitis C and diabetes. Important, although so far limited longitudinal data, have documented an increased risk for diabetes in patients infected by hepatitis C virus (HCV) especially in those with metabolic risk factors such as a high BMI and older age. HCV encoded proteins might alter insulin signalling thus explaining impaired insulin sensitivity and the occurrence of glycaemic dysregulation even before the cirrhotic stage. The consequences of the association between diabetes and HCV infection are an increased liver fibrosis stage and faster fibrosis progression rate. This article reviews recent human and experimental data on the HCV‐diabetes association.
Iron and insulin resistance
Authors: FARGION S. , DONGIOVANNI P. , GUZZO A. , COLOMBO S. , VALENTI L. , FRACANZANI A. L.
Published: October 2005

Background : Preliminary clinical and experimental results suggest that iron can modify hepatocytes’ insulin sensitivity by interfering with insulin receptor and intracellular insulin signalling.

Aim : To evaluate in vivo the influence of iron on insulin resistance and insulin release in patients with non‐alcoholic fatty liver disease and in vitro the interaction between iron and insulin sensitivity by analysing the effect of iron manipulation on insulin receptor expression in hepatoblastoma HepG2 cell line.

Results : Insulin resistance evaluated by homeostatis model assessment (HOMA)‐insulin resistance significantly decreased after diet, and a further reduction was observed after phlebotomies. Iron depletion by desferrioxamine increased by twofold the 125I‐insulin‐specific binding, whereas iron addition reduced insulin binding, similarly to cells exposed to high glucose concentration.

Conclusion : Iron status affects insulin sensitivity by modulating the transcription and membrane expression/affinity of insulin receptor expression in hepatocytes and influencing insulin‐dependent gene expression suggesting that increased insulin clearance and decreased insulin resistance may contribute to the positive effect of iron depletion in patients with non‐alcoholic fatty liver disease.
Incidence, risk factors and clinical course of thiopurine‐induced liver injury in patients with inflammatory bowel disease
Authors: BASTIDA G. , NOS P. , AGUAS M. , BELTRÁN B. , RUBÍN Á. , DASÍ F. , PONCE J.
Published: October 2005

Background : The incidence of thiopurine‐induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies.

Aims : To assess the rate of thiopurine‐induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management.

Methods : A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit.

Results : Abnormal liver function was detected in 21 patients (13%; 95% CI: 7–18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6–16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01–23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1–3.1). γ‐Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95).

Conclusions : The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co‐treated with corticosteroids. γ‐Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.
Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study1
Authors: LABENZ J. , ARMSTRONG D. , LAURITSEN K. , KATELARIS P. , SCHMIDT S. , SCHÜTZE K. , WALLNER G. , JUERGENS H. , PREIKSAITIS H. , KEELING N. , NAUCLÉR E. , ADLER J. , EKLUND S.
Published: October 2005

Background : Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse.

Aim : To compare endoscopic and symptomatic remission rates over 6 months’ maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis.

Methods : Patients with symptoms of gastro‐oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6‐month maintenance therapy phase of the study.

Results : A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention‐to‐treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log‐rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro‐oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001).

Conclusions : Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro‐oesophageal reflux disease symptoms.
Colorectal cancer in Asians: a demographic and anatomic survey in Malaysian patients undergoing colonoscopy
Authors: GOH K.‐L. , QUEK K.‐F. , YEO G. T. S. , HILMI I. N. , LEE C.‐K. , HASNIDA N. , AZNAN M. , KWAN K.‐L. , ONG K.‐T.
Published: October 2005

Background : Colorectal cancer is one of the most common forms of gastrointestinal cancer in the world today. In the Asia–Pacific area, it is the fastest emerging gastrointestinal cancer.

Aim : To determine the basic demographic features of patients with colorectal cancer and the anatomic distribution and characteristics of the tumour in a local Asian population.

Methods : We conducted a review of consecutive patients who had undergone colonoscopy from 1999 to 2003 at the University of Malaya Medical Center, Kuala Lumpur, Malaysia.

Results : Analysis was carried out on 3404 patients who underwent colonoscopy. A total of 228 patients (7%) were diagnosed with carcinoma. The mean age of diagnosis (±s.d.) was 64.4 ± 13.1 years. The male to female ratio was 1.15. Polyps were noted in 470 patients (14%). Polyps detected concomitantly with a colorectal cancer were noted in 55 patients (2%). Four patients (0.1%) were diagnosed to have familial adenomatous polyposis coli. Of the 228 patients 209 (92%) had tumours at only one site whereas 19 (8%) had synchronous lesions. Tumours were mainly left sided [198 of 248 patients (80%)] with the majority located in the recto‐sigmoid region. Detailed records of treatment were available only in 176 patients. A total of 147 of 176 patients (84%) underwent surgery and 50 (28%) also received adjuvant or palliative chemotherapy (28%). Seven of 154 patients (5%) were diagnosed to have stage A cancers, 64 (42%), stage B, 23 (15%), stage C and 60 (39%), stage D. Multivariate analysis using multiple logistic regression analysis showed that age ≥65 years (OR = 1.78; 95% CI: 1.35– 2.36) and Malay (OR = 2.09; 95% CI: 1.30–3.35) and Chinese (OR = 1.77; 95% CI: 1.77–2.69) race were significant independent predictive factors for colorectal cancer.

Conclusions : The demography of colorectal cancer is different from western patients. Tumours were mainly left sided in our patients. However, no differences in anatomic location were found between races, men and women and younger and older age groups. Colorectal cancer presented in an advanced stage in the majority of patients.
Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin
Authors: YEOMANS N. D. , LANAS A. I. , TALLEY N. J. , THOMSON A. B. R. , DANESHJOO R. , ERIKSSON B. , APPELMAN‐ESZCZUK S. , LÅNGSTRÖM G. , NAESDAL J. , SERRANO P. , SINGH M. , SKELLY M. M. , HAWKEY C. J.
Published: October 2005

Background : Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk‐benefit decisions in individual patients.

Aim : To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors.

Methods : Patients taking aspirin 75–325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non‐steroidal anti‐inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants).

Results : In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3–15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4–11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3–149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3–8.7).

Conclusions : Gastroduodenal ulcers are found in one in 10 patients taking low‐dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).
Effects of ferrous sulphate and non‐ionic iron–polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease
Authors: ERICHSEN K. , ULVIK R. J. , GRIMSTAD T. , BERSTAD A. , BERGE R. K. , HAUSKEN T.
Published: October 2005

Background : Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species.

Aim : To compare the effects of ferrous sulphate and non‐ionic iron–polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease.

Methods : Forty‐one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron–polymaltose complex 200 mg once a day for 14 days.

Results : Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8‐isoprostaglandin F2α and plasma antioxidants did not change significantly. Iron–polymaltose complex did not change plasma malondialdehyde, urine 8‐isoprostaglandin F2α or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8‐isoprostaglandin F2α and plasma antioxidants did not differ. Neither ferrous sulphate nor iron–polymaltose complex altered clinical disease activity indices.

Conclusions : Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron–polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.
Evaluation of the Ez‐HBT Helicobacter blood test to establish Helicobacter pylori eradication
Authors: AHMED F. , MURTHY U. K. , CHEY W. D. , TOSKES P. P. , WAGNER D. A.
Published: October 2005

Background : The urea blood test (Ez‐HBT) has been shown to compare favourably with the urea breath test in the diagnosis of active Helicobacter pylori infection.

Aim : To examine the performance characteristics of the Ez‐HBT Helicobacter blood test in establishing success or failure of therapy in H. pylori‐infected adults using the 13C urea breath test as the reference method.

Methods : 13C urea breath test and Ez‐HBT Helicobacter blood test were performed 4–6 weeks after completion of treatment in H. pylori positive subjects. Basal urea breath samples were collected; basal Ez‐HBT Helicobacter blood test samples were not. Ez‐HBT Helicobacter blood test results were reported as positive, negative, or indeterminate.

Results : Seventy patients generated 126 measurable sets of urea breath and blood tests. The H. pylori cure rate was 93%. The sensitivity, specificity, and accuracy of the Ez‐HBT Helicobacter blood test were 100%, 97%, and 97%, respectively. Six of eight false positive and indeterminate Ez‐HBT Helicobacter blood test results could be attributed to incomplete fasting or a 13C enriched diet. After correcting for the non‐fasting state, the positive predictive value of the Ez‐HBT Helicobacter blood test improved from 56% to 86%.

Conclusion : The performance characteristics of the Ez‐HBT Helicobacter blood test are comparable with that of 13C‐urea breath test in establishing H. pylori eradication after therapy. Errors related to incomplete fasting can be mitigated by collection of a basal blood sample.
The fractal nature of human gastro‐oesophageal reflux
Authors: GARDNER J. D. , YOUNG W. , SLOAN S. , ROBINSON M. , MINER P. B.
Published: October 2005

Background : We are unaware of the analyses of time series data resulting from 24 h recordings of human gastric or oesophageal pH. As a result, we have no understanding of the quantitative changes in gastric or oesophageal acidity over time, the patterns that might characterize these changes, or the physiological significance of gastro‐oesophageal reflux.

Aim : To examine the time series for gastric and oesophageal pH.

Methods : Detrended fluctuation analysis and lag analysis were used to analyse data from 24 h recordings of oesophageal and gastric pH in five normal subjects and five subjects with gastro‐oesophageal reflux disease.

Results : Analyses of the patterns of gastric and oesophageal pH over time in normal subjects and subjects with gastro–oesophageal reflux disease indicate that the fluctuations in pH are self‐similar across different time scales and are consistent with an underlying fractal process. Furthermore, there is a significant statistical association between sequential pH values separated by as much as 2.2 h.

Conclusions : We hypothesize that the self‐similar, fractal pattern encodes information about gastric acidity and that the oesophagus decodes this information and, when appropriate, may signal the stomach to reduce gastric acidity. Subjects with gastro‐oesophageal reflux disease might have an impaired oesophageal–gastric feedback mechanism that results in increased gastric acid, which reflux from the stomach into the oesophagus.
Homozygosity for human leucocyte antigen‐C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen‐C‐matched unrelated donor haematopoietic stem cell transplantation
Authors: Giebel Sebastian , Locatelli Franco , Wojnar Jerzy , Velardi Andrea , Mina Tommaso , Giorgiani Giovanna , Krawczyk‐Kulis Malgorzata , Markiewicz Miroslaw , Wylezol Iwona , Holowiecki Jerzy
Published: October 2005

Human leucocyte antigen (HLA)‐C molecules regulate the function of natural killer cells and may be subdivided into two groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin‐like receptors. We analysed the impact of the HLA‐C genotype on outcome of HLA‐C‐matched unrelated donor haematopoietic stem cell transplantation (URD‐HSCT) recipients. HLA‐C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0·01) and disease‐free survival (P = 0·02), resulting from increased relapse rate (P = 0·02) when compared with both HLA‐C(1) homozygous (n = 43) and HLA‐C(1),C(2) heterozygous (n = 50) subgroups. Patients lacking HLA‐C(1) should, therefore, be considered at increased risk of relapse following HLA‐C‐matched URD‐HSCT.
Glomerulonephritis, Th1 and Th2: what's new?
Authors: Tipping P G , Kitching A R
Published: October 2005

Glomerulonephritis (GN), the major worldwide cause of chronic renal disease and renal failure, shows a wide spectrum of histological patterns, severity of injury and clinical outcomes that may be related to the nature of the nephritogenic immune response. In the majority of cases, there is evidence of a central role for cognate immunity in the initiation of human GN and contributions of both humoral and cellular effector mechanisms have been demonstrated in both humans and in animal models. T helper cell subsets are known to activate different immune effector mechanisms which influence disease outcomes in infectious and autoimmune diseases and evidence is now accumulating that Th1 and Th2 subsets direct diverging effector pathways that lead to different patterns and severity of glomerular injury in GN. Th1-predominant responses appear to be associated strongly with proliferative and crescentic forms of GN that result in severe renal injury, while Th2 responses are associated with membranous patterns of injury. The challenge remains to understand fully the relevance of T helper cell subset responses to the spectrum of human GN and to apply this new knowledge to the development of more potent and selective therapeutic strategies.
Dental anomalies in Axenfeld–Rieger syndrome
Authors: O'DWYER E. M. , JONES D. C.
Published: October 2005

Summary. The authors describe the case of a 10‐year‐old girl presenting with Axenfeld–Rieger syndrome (ARS), a rare autosomal dominant condition. The patient showed severe hypodontia, microdontia and short roots. Early diagnosis of the syndrome from its dento‐facial and systemic features is important so that subsequent ocular complications may be prevented.