bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNATargets: A platform for lncRNA target prediction based on nucleic acid thermodynamics
Authors: Hu Ruifeng , Sun Xiaobo
Published: March 2016

Many studies have supported that long noncoding RNAs (lncRNAs) perform various functions in various critical biological processes. Advanced experimental and computational technologies allow access to more information on lncRNAs. Determining the functions and action mechanisms of these RNAs on a large scale is urgently needed. We provided lncRNATargets, which is a web-based platform for lncRNA target prediction based on nucleic acid thermodynamics. The nearest-neighbor (NN) model was used to calculate binging-free energy. The main principle of NN model for nucleic acid assumes that identity and orientation of neighbor base pairs determine stability of a given base pair. lncRNATargets features the following options: setting of a specific temperature that allow use not only for human but also for other animals or plants; processing all lncRNAs in high throughput without RNA size limitation that is superior to any other existing tool; and web-based, user-friendly interface, and colored result displays that allow easy access for nonskilled computer operators and provide better understanding of results. This technique could provide accurate calculation on the binding-free energy of lncRNA-target dimers to predict if these structures are well targeted together. lncRNATargets provides high accuracy calculations, and this user-friendly program is available for free at http://www.herbbol.org:8001/lrt/ .
China's Politics: Bold Reforms and Unabated War on Corruption
Authors: ZHENG Yongnian , CHEN Gang
Published: March 2016

In 2015, the XI administration snared 30 ministerial-and-above officials including Guo Boxiong of the Central Military Commission for corruption; abolished the long-delayed one-child policy; restructured state-owned enterprises; and overhauled the military by rejigging existing military regions and executing a cut of 300,000 army personnel. In the stock market meltdown, many officials, securities brokers and fund managers were arrested for insider trading and market manipulation. The stabilisation of the market laid the foundation for many long-awaited financial reforms.
A Game-Theory Approach for Effective Crowdsource-Based Relevance Assessment
Authors: Moshfeghi Yashar , Rosero Alvaro Francisco Huertas , Jose Joemon M.
Published: March 2016

Despite the ever-increasing popularity of crowdsourcing (CS) in both industry and academia, procedures that ensure quality in its results are still elusive. We hypothesise that a CS design based on game theory can persuade workers to perform their tasks as quickly as possible with the highest quality. In order to do so, in this article we propose a CS framework inspired by then-person Chicken game. Our aim is to address the problem of CS quality without compromising on CS benefits such as low monetary cost and high task completion speed. With that goal in mind, we study the effects of knowledge updates as well as incentives for good workers to continue playing. We define a general task with the characteristics of relevance assessment as a case study, because it has been widely explored in the past with CS due to its potential cost and complexity. In order to investigate our hypotheses, we conduct a simulation where we study the effect of the proposed framework on data accuracy, task completion time, and total monetary rewards. Based on a game-theoretical analysis, we study how different types of individuals would behave under a particular game scenario. In particular, we simulate a population comprised of different types of workers with varying ability to formulate optimal strategies and learn from their experiences. A simulation of the proposed framework produced results that support our hypothesis.
Universal Artifacts
Authors: Sun Yutian , Su Jianwen , Yang Jian
Published: March 2016

In most BPM systems (a.k.a. workflow systems), the data for process execution is scattered across databases for enterprise, auxiliary local data stores within the BPM systems, and even file systems (e.g., specification of process models). The interleaving nature of data management and BP execution and the lack of a coherent conceptual data model for
all
data needed for execution make it hard for (1) providing Business-Process-as-a-Service (BPaaS) and (2) effective support for collaboration between business processes. The primary reason is that an enormous effort is required for maintaining both the engines and the data for the client applications. In particular, different modeling languages and different BPM systems make process interoperation one of the toughest challenges. In this article, we formulate a concept of a “universal artifact,” which extends artifact-centric models by capturing
all needed data
for a process instance throughout its execution. A framework called SeGA based on universal artifacts is developed to support separation of data and BP execution, a key principle for BPM systems. We demonstrate in this article that SeGA is versatile enough to fully facilitate not only executions of individual processes (to support BPaaS) but also various collaboration models. Moreover, SeGA reduces the complexity in runtime management including runtime querying, constraints enforcement, and dynamic modification upon collaboration across possibly different BPM systems.
Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease
Authors: Iwashita Yoshihiro , Kuwabara Takashige , Hayata Manabu , Kakizoe Yutaka , Izumi Yuichiro , Iiyama Junichi , Kitamura Kenichiro , Mukoyama Masashi
Published: March 2016

Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.
Receptive field size, chemical and thermal responses, and fiber conduction velocity of rat chorda tympani geniculate ganglion neurons
Authors: Yokota Yusuke , Bradley Robert M.
Published: March 2016

Afferent chorda tympani (CT) fibers innervating taste and somatosensory receptors in fungiform papillae have neuron cell bodies in the geniculate ganglion (GG). The GG/CT fibers branch in the tongue to innervate taste buds in several fungiform papillae. To investigate receptive field characteristics of GG/CT neurons, we recorded extracellular responses from GG cells to application of chemical and thermal stimuli. Receptive field size was mapped by electrical stimulation of individual fungiform papillae. Response latency to electrical stimulation was used to determine fiber conduction velocity. Responses of GG neurons to lingual application of stimuli representing four taste qualities, and water at 4°C, were used to classify neuron response properties. Neurons classified as SALT, responding only to NaCl and NH4Cl, had a mean receptive field size of six papillae. Neurons classified as OTHER responded to salts and other chemical stimuli and had smaller mean receptive fields of four papillae. Neurons that responded to salts and cold stimuli, classified as SALT/THERMAL, and neurons responding to salts, other chemical stimuli and cold, classified as OTHER/THERMAL, had mean receptive field sizes of six and five papillae, respectively. Neurons responding only to cold stimuli, categorized as THERMAL, had receptive fields of one to two papillae located at the tongue tip. Based on conduction velocity most of the neurons were classified as C fibers. Neurons with large receptive fields had higher conduction velocities than neurons with small receptive fields. These results demonstrate that GG neurons can be distinguished by receptive field size, response properties and afferent fiber conduction velocity derived from convergent input of multiple taste organs.
Symptomatic Improvement of Gastroduodenal Crohn’s Disease with Omeprazole
Authors: Woolfson K , Greenberg GR
Published: March 2016

Four patients with ileal Crohn’s disease presented with abdominal pain aggravated by food, a mean weight loss of 5.5 kg (range 4 to 7) and ulceration of the antrum and/or duodenum at gastroscnpy, without radiological features of mechanical obstruction . The endoscopic and histological appearance of the ulcers was consistent with Crohn's disease. Omeprazole 40 mg daily was administered, without other drugs, and after three days of therapy patients were asymptomatic. After eight weeks of omeprazole, a mean weight gain of 6 kg (range 3 to 10) had occurred and the drug was withdrawn. One patient remained well and three patients relapsed, but all responded to long term omeprazole for up to three years. Follow-up endoscopies have indicated healing in one patient, partial healing in two patients and no change in one patient. Omeprazole may be of value in the symptomatic management of patients with gastroduodenal Crohn’s disease.
Percutaneous Gastronomy and Jejunostomy: Lessons from the First Decade
Authors: Goff John S
Published: March 2016

Percutaneous gastrostomies and jejunostomies have increasingly been used for long term enteral feeding in patients with functioning gastrointestinal tracts but who are unable, for a variety of reasons, to use the standard oropharyngeal route. Since these devices can be placed without the use of general anesthesia, the morbidity and mortality generally are less than for placement of a surgical gastrostomy. A permanent gastrostomy tube is easy to manage in most patients who require prolonged tube feeding. There are four basic types of percutaneous gastrostomy techniques; three employ an endoscope and one uses only radiographic or ultrasonic guidance. All gastrostomy tubes may be convened to feeding jejunostomies if the clinical situation warrants. Jejunal feeding tubes are prone to many technical problems and do not always solve the problems of gastric dysfunction and reflux that make gastrostomy tubes less desireable. Percutaneous endoscopic gastrostomics are technically simple to perform and have become the main method for access to the gastrointestinal tract in many patients. If judiciously used, the percutaneous enterostomy offers many benefits over a nasogastric tube for long term enteral feeding.
Isolation of Klebsiella Pneumoniae from an Hepatic Inflammatory Pseudotumour
Authors: Malatjalian Dickran K , Morris John , Bodurtha Audley
Published: March 2016

lnflammatory pseudotumours of the liver are rare, solid mass lesions (often mistaken for malignancy) and although inflammatory in nature, are obscure in etiology and pathogenesis. An hepatic inflammatory pseudotumour is presented in which cultures obtained from the lesion intraoperatively grew Klebsiella pneumoniae. This is the first case of an hepatic inflammatory pseudotumour in which a microorganism has been identified. The isolation of K pneumoniae suggests that inflammatory pseudotumours may arise from a low grade infection with chronic inflammatory tissue response.
Renal Aspects of Peptic Ulcer Pharmacology
Authors: Muruve Daniel , Burgess Ellen
Published: March 2016

Medications to treat peptic ulcer disease are used widely and may have adverse effects on renal function. Similarly, renal dysfunction may alter the pharmacokinetics of this diverse group of medications resulting in dosage adjustments. The older agents, antacids and sucralfate, allow absorption of cations (calcium, magnesium and aluminum) which may result in toxicity. Newer medications (H2blockers and omeprazole) appear to have fewer side effects and be better tolerated with appropriate dosage adjustments.
Inflammatory Bowel Disease, the Oral Contraceptive Pill and Pregnancy
Authors: Allan Robert N
Published: March 2016

This paper summarizes our current knowledge of the role of the oral contraceptive pill in the pathogenesis of inflammatory bowel disease (IBO), followed by a review of fertility in women and men. IBD and pregnancy, including the impact on the fetus and the mother with ulcerative colitis or Crohn’s disease, is considered. The safety of drug treatment during pregnancy, the outcome of surgical treatment during pregnancy and the problems that may be encountered during pregnancy in patients with an ileostomy or ileo‐anal pouch are discussed, followed by a review of the short and long term prognosis of ulcerative colitis and Crohn’s disease partition.
Cimetidine Pharmacodynamics and Pharmacokinetics in Healthy Subjects: A Comparison of Tablets and Suspension
Authors: Thomson ABR , Kirdeikis P , Zuk L , Samuels RE , Zarevics P
Published: March 2016

The objective of this study was to compare the effect of cimetidine 200 mg tablet with that of cimetidine suspension (200 mg/10 mL), a 20 mL suspension of 800 mg magnesium hydroxide and 912 mg aluminum hydroxide, and matching placebo on intragastric pH of healthy volunteers. There were 13 males and seven females, mean age 23 years (range 20 to 32) and mean weight 72 kg (range 55 to 89). The intragastric pH of each subject was measured over 6 h starting immediately before dosing on each of five study days. Cimetidine plasma levels were measured for 6 h after dosing on each of the cimetidine study days. Cimetidine tablet and suspension were superior to placebo tablet or suspension or to the magnesium hydroxide/aluminum hydroxide suspension in the area under the pH time curve from 0 to 6 h, percentage time pH of at least 3.5, change from pretreatment pH area under the pH time curve (0 to 6 h) and maximum increase in pH. Mean plasma cimetidine levels were significantly and positively correlated to mean intragastric pH for both cimetidine tablets and cimetidine suspension. Comparing cimetidine concentration (Cmax) and lower percentage time plasma cimetidine concentration was at least 0.5 μg/mL (the minimum therapeutic level). These pharmacokinetic variations between cimetidine suspension and tablets may have partially explained the pharmacodynamic differences of the lower area under the pH time curve (0 to 6 h). The results indicate that both cimetidine tablets and cimetidine suspension significantly increase intragastric pH relative to the magnesium hydroxide/aluminum hydroxide suspension, placebo tablets or placebo suspension. Based on the assumption that elevation of intragastric pH is an important factor for alleviation of the symptoms and for the healing of peptic disorders, the results of this study suggest that both cimetidine tablets and cimetidine suspension should be effective treatment.
Granulomatous Vasculitis and Persistent Measles Virus Infection in Crohn’s Disease
Authors: Wakefield AJ
Published: March 2016

Based upon the recent observation of vasculitis in Crohn’s disease, a process that is more widespread than was recognized previously, the author investigated the possibility that this mechanism may provide an explanation for some of the clinical and histological idiosyncracies of this condition. In addition, it was suggested that the mesenteric microvascular endothelium may be a source of the persistent antigen that is responsible for ongoing cellular immunity in Crohn’s disease. This review discusses some of the studies designed to test these hypotheses, and discusses recent evidence for the presence of a measles-like virus in the endothelium in inflammatory foci, which may be relevant in the etiology of Crohn’s disease.
Medical Tretment of Peptic Ulcer Disease: Should the Emphasis Be Altered in View of Laparoscopic Surgery
Authors: Thomson ABR
Published: March 2016

In the past H2-receptor antagonist era, there was initially a lull as more and more ‘me-too’ drugs were developed. Then came the excitement of the proton pump inhibitors and the controversy of the pros and cons of moderate versus potent acid inhibition. The most recent explosion of knowledge has been in the discussion of pH versusHelicobacter pylori, but on the horizon is lurking the promise of the resurgence of the surgical option.
Use of 24 h Esophageal pH Monitoring to Demonstrate Alkaline Reflux as a Complication of Gastric Bypass Surgery
Authors: Shoenut J Patrick , Danzinger Rudy G
Published: March 2016

A 35-year-old female who had previously undergone a gastric stapling procedure for morbid obesity presented with a persistent nocturnal cough that was treated over a three-year period as a gastric acid reflux complication of the bypass surgery. A barium swallow demonstrated gastroesophageal reflux, but the symptoms did not resolve after treatment with omeprazole and cisapride. Twenty-four hour esophageal pH monitoring subsequently found alkaline reflux in excess of 17% of the total time, with no acid reflux demonstrated. Surgical revision of the bypass Leaving the hiatus alone corrected the reflux complication and the symptoms resolved without further treatment. The diagnostic capability of pH monitoring is illustrated in a patient with an unusual surgical complication.
Overview of 5-ASA in Therapy of Inflammatory Bowel Disease
Authors: Williams CN
Published: March 2016

There are two forms of 5-aminosalicylic acid (5-ASA) drug delivery. First, a pro-drug form in which 5-ASA, the active principal, is attached to a c.arrier molecule and released in the intestine by bacterial cleavage. An example of this is sulfasalazine, originally developed in the 1940s and found to be effective, cheap, but limited by side effects due to the sulfapyridine component. The second drug delivery system depends on an enteric coating for delayed pH-dependent release or for a timed-released mechanism. 5-ASA inhibits 5-lipoxygenase, modulates leukocyte function and inhibits soluble mediator release, and is an effective scavenger action of free oxygen radicals, the relative importance of which is unknown. The multiplicity of action is probably its strength because drugs that have only one of these actions are relatively ineffective in inflammatory bowel disease. 5-ASA compounds are effective in treating mild to moderate acute ulcerative colitis and in maintaining remission, and are equivalent to sulfasalazine in this regard. 5-ASA used topically in enema or suppository form is highly efficient in both acute disease and in maintaining remission. 5-ASA is also effective in active Crohn’s disease, but not as effective as in maintenance therapy compared with ulcerative colitis. The pro-drugs tend to have more side effects. Slow release compounds are well tolerated with few side effects, allowing increases to effective dosage. In patients intolerant of sulfasalazine, switching to a 5-ASA preparation usually results in tolerance and therapeutic benefit, with an occasional allergic reaction to the 5-ASA molecule limiting its use.
A Potential Prognostic Indicator of Fulminant Hepatic Failure: A Valuable Adjunct in Preliver Transplant Assessment
Authors: Yacyshyn B , Cheung CM , Malkin D Gordon , Pappas SC
Published: March 2016

The use of thyroid function tests as a method of monitoring patients with fulminant hepatic failure has been previously proposed. The use of these indices in two cases with fulminant hepatic failure are described. Both patients had simultaneous ingestion of hepatotoxic mushroom (amanita virosa). Their parallel clinical courses and recovery without liver transplantation is described, outlining the potential long term cost-savings achievable by such tests in the selection of patients for liver transplantation and the need for further study of these indices for this application.
Helicobacter pylori: Beginning the Second Decade
Authors: Matisko Ann , Thomson ABR
Published: March 2016

‘Beginning the Second Decade’ ‐ a recent international meeting on Helicobacter pylori ‐ was held in conjunction with the VIIth International Workshop on Gastroduodenal Pathology and H pylori and with the meeting of the European Helicobacter pylori Study Group in Houston, Texas from September 30 to October 1, 1994. A menu of 476 abstracts, published in the American Journal of Gastroenterology (1994;89:8), highlighted the explosion of advances in this area. The Houston meeting was followed by the Tenth World Congresses of Gastroenterology from October 2 to 7, 1994 in Los Angeles, California, again with scores of presentations and posters on topics ranging from the epidemiology of H pylori infection to steps towards the development of a human vaccine. All this was in addition to important new work presented earlier in 1994 in New Orleans during Digestive Diseases Week. In this digest of these important meetings, the authors will not regurgitate what the informed reader already knows, but will instead focus on the recent developments in important areas, providing selected key published references for background, and referring to this new work in abstract form which is at the cutting edge of “yesterday’s tomorrow today”.
Helicobacter pylori: Basic Mechanisms to Clinical Cure
Authors: Thomson ABR , Williams CN
Published: March 2016

Since its rediscovery 10 years ago,Helicobacter pylorihas reshaped our thinking about the course of peptic ulcer disease. Our approach to the patient with a duodenal ulcer has become one of attempting eradication therapy at the time of first diagnosis, in the hope of curing the ulcer disease. Gastric and duodenal ulceration are only two of the manifestations of this chronic antral infection; other complications ofH pyloriinclude gastritis, gastric cancer and possible maltomas. Therapy ofH pyloriinfection is complicated and involves dual therapy with an antibiotic plus a protein pump inhibitor, such as omeprazole 20 mg bid plus amoxicillin 1 g bid for two weeks, triple or quadruple therapy with bismuth, two antibiotics and an H2-receptor antagonist. Vaccination againstH pyloriis on the far horizon.
Atypical Manometric Abnormality of the Lower Esophageal Sphincter: A Procedure‐Related, Stress‐Induced Phenomenon?
Authors: Indrakrishnan Bhuvanendram , Paterson William G
Published: March 2016

Stress‐induced esophageal contraction abnormalities have been well documented in the literature, but relatively little is known about stress‐related lower esophageal sphincter (LES) dysfunction. Two patients are described in whom initial manometry studies revealed LES hypertension and impaired LES relaxation. Both patients were markedly anxious and agitated during the initial study. However, when the manometry was repeated with the patients in a calmer state, LES pressure and function were normal. These cases demonstrate the need to be aware of stress‐related LES dysfunction. If this phenomenon is not identified in the appropriate settings, it could lead to significant errors in management.
Potential Human Models of Infammatory Bowel Disease
Authors: Hanauer Stephen B
Published: March 2016

Similar to animal models of inflammatory bowel disease (IBD), there is no single human model representative of ulcerative colitis or Crohn′s disease. An optimal human model awaits etiopathogenetic definitions and further reclassification or depiction of clinicopathological scenarios. Current human models can be classified into models depicting risk of disease; preclinical disease; acute inflammation; and miscellaneous IBD. Family studies are the best means of pursuing patients at risk. Evolving genetic and serological markers may further identify subgroups to assess with permeability probes, leukocyte scans or endoscopy for preclinical disease. Provocation with nonsteroidal anti‐inflammatory drugs (NSAIDs) may be useful in selected patients because NSAID mucosal damage may induce or mimic IBD. Alternative natural history or interventional studies in patients with human leukocyte antigen (HLA)‐B27 spondylarthropathy may be useful. The disease margin and pouchitis are models within the disease state of ulcerative colitis as are the aphthous ulcer, anastomotic margin and diverted fecal stream for Crohn′s disease. Newly defined colitides, such as microscopic and collagenous colitis and diversion colitis, also provide potential comparative models to evaluate mucosal immune, inflammatory, reparative, secretory and absorptive regulation.
Celiac‐Associated Autoimmune Thyroid Disease: A Study of 16 Patients with Overt Hypothyroidism
Authors: Freeman Hugh J
Published: March 2016

Previous reports have suggested that autoimmune thyroid disorders (including Hashimoto’s or lymphocytic thyroiditis) may occur in patients with celiac disease. In this study, the prevalence of thyroid disease was explored in a series of 96 consecutive patients seen with biopsy‐defined adult celiac disease (average age 47.3 years). Sixteen celiac patients (average age 58.1 years) were detected with hypothyroidism, including four treated with radio‐iodine ablation or thyroidectomy for Grave’s disease. In addition to celiac disease, almost half had dermatitis herpetiformis, a small intestinal neoplasm (particularly lymphoma) or both. Diagnosis of thyroid disease preceded diagnosis of celiac disease in 13 patients or was made concurrently in two patients. In only one patient was thyroid disease detected after celiac disease was diagnosed. This indicates that thyroid diseases occur more commonly in celiac disease than is currently appreciated, possibly due to shared embryological origins or common immunopathological features, and may be the presenting clinical manifestation in adults especially if there is coexistent dermatitis herpetiformis. Careful monitoring of this subgroup may be warranted because of the frequency of neoplastic intestinal diseases, particularly lymphoma.
Clinical Aspects of Trace Elements: Zinc in Human Nutrition – A Biochemical and Physiological Perspective
Authors: Pluhator Michelle M , Thomson Alan BR , Fedorak Richard N
Published: March 2016

The tremendous technological advances in trace element analysis seen in recent years have stimulated and facilitated research in a number of disciplines including microbiology, nutrition, agriculture, clinical medicine and, most recently, psychology. The importance of trace elements to human health is receiving greater attention as clinical cases of deficiency and toxicity are described. Zinc has been recognized as an essential trace element for humans since the early 1960s. It has been found to play a critical role in the physiological and biochemical well‐being of humans. This review discusses the tissue distribution, concentration and intracellular binding of zinc in healthy humans. (Other reviews in this five‐part series will appear in following issues.) The biochemical roles of zinc, including its involvement in the actions of metalloenzymes, cell synthesis, wound healing, growth, reproduction, hormone metabolism, cellular structural stability and immunological processes, are highlighted in order to provide an understanding of the unique and extensive role zinc plays in the biochemistry of the human body.
Cancer Risk in Inflammatory Bowel Disease
Authors: Ekbom Anders M
Published: March 2016

There is an increased risk of cancer in both ulcerative colitis and Crohn′s disease. In 3121 patients with ulcerative colitis, 225 cases of cancer were diagnosed compared with 142.1 expected (standardized incidence ratio [SIR] 1.6, 95% CI 1.4 to 1.8), and in 1655 patients with Crohn′s disease, 58 cases of cancer were detected compared with 47.1 expected (SIR 1.2, 95% CI 0.9 to 1.6). After excluding colorectal cancer the observed number of malignancies was very close to that expected for ulcerative colitis (SIR 1.0, 95% CI 0.9 to 1.2) and for Crohn′s disease (SIR 1.1, 95% CI 0.8 to 1.5). Thus, the increased risk of cancer in inflammatory bowel disease is confined to colorectal cancer. In Crohn′s disease 12 cases of colorectal cancer were observed (SIR 2.5, 95% CI 1.3 to 4.3). The increased risk was confined to those with colonic involvement and young age at diagnosis. In patients with colonic involvement and younger than age 30 years at diagnosis, the SIR was 20.9 (95% CI 6.8 to 48.7) versus 2.2 for those older than 30 years at diagnosis (95% CI 0.6 to 5.7). In ulcerative colitis 91 cases of colorectal cancer were observed with an SIR of 5.7 (95% CI 4.6 to 7.0). Extensive disease and young age at diagnosis were independent risk factors. Pancolitis at diagnosis resulted in an SIR of 14.8 (95% CI 11.4 to 18.9), 2.8 in left‐sided colitis (95% CI 1.6 to 4.4) and 1.7 in proctitis (95% CI 0.8 to 3.2). There is great variation in the risk estimates in different studies worldwide. Different treatment strategies could be an explanation, a hypothesis that was substantiated in a study of 102 cases of colorectal cancer among patients with ulcerative colitis compared with 196 controls. Pharmacological therapy with sulfasalazine entailed a strong protective effect against colorectal cancer (relative risk of 0.34, 95% CI 0.190 to 0.62).
Subclinical Markers of Human Inflammatory Bowel Disease
Authors: Yang Huiying , Rotter Jerome I
Published: March 2016

Genetic studies can be greatly aided by the use of subclinical markers that are closer to the basic defect and thus likely to detect more individuals with the abnormal genotype. At least two approaches are generally used to characterize subclinical markers. One is the family study approach. The detection of subclinical abnormalities in unaffected relatives similar to those found in the probands can distinguish between an inherited predisposition and a secondary abnormality due to the disease process. The second approach is the combination of subclinical marker with genetic marker studies. Specific association of a subclinical marker with a genetic marker indicates genetic determination of the subclinical marker. The identification of a genetically determined subclinical marker can help to define a more homogeneous disease group for genetic studies. The most studied subclinical markers in inflammatory bowel disease (IBD) are antineutrophil cytoplasmic antibodies (ANCAs) for ulcerative colitis (UC) and intestinal permeability for Crohn′s disease (CD). Even so, for these as well as several other promising subclinical markers, there is an obvious need for more twin, family and genetic marker studies. An elevated intestinal permeability in a proportion of unaffected relatives of CD patients has been observed in the majority of family studies. ANCAs, a highly specific marker for UC, have been found with a significantly increased prevalence in unaffected relatives of UC patients compared with spouses of the patients. Moreover, the distribution of the ANCAs is familial rather than random, suggesting heterogeneity within UC. In combination with genetic marker studies (human leukocyte antigen [HLA] class II genes), the authors observed a differential association: ANCA‐positive UC was associated with DR2, while ANCA‐negative UC associated with DR4. These data lead to the conclusion that the heterogeneity indicated by ANCA is genetically determined and that this genetic heterogeneity should be taken into consideration in future genetic, clinical and pathophysiological studies. In the aggregate, these data indicate that the subclinical marker approach is a powerful means for demonstrating genetic and etiological heterogeneity, and can be an important tool to define the etiology and natural history of the various diseases that make up IBD.
Active Specific Immunotherapy in the Management of Adenocarcinoma of the Pancreas
Authors: Yacyshyn BR , Longenecker BM , Biermann WA , McClure D , Poppema S , Bowen-Yacyshyn MB
Published: March 2016

Active specific immunotherapy for pancreatic adenocarcinoma and subsequent immunohistochemical analysis of tumour tissue have not been previously reported. To date, the therapy of pancreatic adenocarcinoma has been largely unsuccessful. A patient treated with a therapeutic ‘cancer vaccine’ and the immunological impact on the primary tumour of this potential new therapy are described. To the authors’ knowledge, this is both the first patient to be treated with active specific immunotherapy for pancreatic adenocarcinoma and the first to be studied immunologically by flow cytometry and immunohistochemistry with an apparent positive clinical impact.
Clinical Aspects of Trace Elements: Zinc in Human Nutrition – Zinc Requirements
Authors: Pluhator Michelle M , Thomson Alan BR , Fedorak Richard N
Published: March 2016

The body requires certain levels of essential nutrients, such as zinc, to maintain life. Intake less than the required levels can cause impaired function, disease and death. Every essential nutrient has a unique range of tissue concentration and intake necessary for proper physiological and biochemical functioning. Many criteria have been used to set dietary intake levels for nutrients. For trace elements, however, a limited number of investigative approaches are currently employed by researchers due to inadequate information on individual requirements and intake levels. Further, a clear lack of satisfactory biochemical methods to measure zinc nutritional status continues to hinder formulation of dietary guidelines. Thus, many assumptions have to be made, and large safety margins have to be added to assumed daily requirements in order to compensate for this absence of information. Numerous barriers to a full understanding of what constitutes an adequate dietary recommendation for zinc still exist. Zinc is incompletely absorbed, and this absorption can be greatly influenced by the chemical form in which zinc is bound; interactions with other nutrients also affect absorption. Part three of this five-part review presents the current Canadian recommended nutrient intakes for zinc for various sex and age categories and provides a rationale for the suggested values. The important nutrient interactions that affect the bioavailability of zinc, including those with phytates, copper, cadmium, tin and iron, are discussed.
Fatal Cholestatic Hepatitis in an Infant: An Unusual Etiology
Authors: Oliver Mark R , Pinto Alfredo , Scott R Brent
Published: March 2016

An infant girl who presented with cholestasis and hepatitis that rapidly progressed to fulminant liver failure is reported. Postmortem examination yielded a diagnosis of demonstrated extensive hepatic necrosis due to adenovirus type 5 infection which had developed in the setting of an occult primary immunodeficiency (severe combined immunodeficiency). The aim of this report is to alert the physician to a rare cause of cholestasis and hepatitis in infancy. Recognition of the combination of adenoviral infection with underlying primary immunodeficiency is a prerequisite to the provision of genetic counselling.
Childhood Ménétriér′s Disease: A Rare Cause of Exudative Enteral Protein Loss
Authors: Oliver Mark R , Trevenen Cynthia , Scott R Brent
Published: March 2016

A six‐year‐old boy with Ménétriér′s disease, which developed in association with an intercurrent cytomegalovirus (CMV) infection, is presented. This case illustrates the clinical features, natural history and self‐limited nature of this rare cause of exudative protein loss in childhood and provides evidence for the association between CMV infection and the pathogenesis of this disorder.
Management of Radiation‐Induced Proctitis
Authors: Anderson Frank H , Zeng Lecheng
Published: March 2016

The acute form of radiation intestinal injury is usually transient and self‐limited, while chronic injury is permanent and progressive, and its management is unsatisfactory. As reported recently, however, several treatment options are available to control symptoms reasonably in most cases. Some approaches are of particular interest due to their efficacy, availability and simplicity. More clinical evaluations are required to confirm this initial enthusiasm.
Genetics of Complex Disease: From Mouse to Man and Back
Authors: Warden Craig H , Rotter Jerome I
Published: March 2016

Identification of genes underlying complex traits has been difficult, but combined application of novel methods and mouse models provides new hope. Rare monogenic syndromes, and candidate gene and biochemical approaches are sometimes useful, but each of these approaches also has limitations. Some problems that prevent identification and isolation of genes underlying complex disease can be avoided by the use of whole genome mapping of mouse crosses or of human families. Mice have many advantages for the study of complex disease, including an extensive genetic map. A generic method has recently been developed and applied for detection of quantitative trait loci (QTLs) using whole genome maps of mouse crosses. Availability of more than 200 congenic strains provides another incentive for studies in mice. Congenic strains provide a rich, but previously unexploited, resource for the rapid identification of genes causing complex diseases. A congenic mouse strain is genetically identical to a background strain, except for a small chromosomal region derived from a donor strain. Thus, comparison of a phenotype in a congenic strain with the phenotype in its background strain allows study of the effects of single genes derived from the donor strain, isolated from the effects of other donor strain genes. Application of all or several techniques to complex disease studies in mice and in humans may lead to the identification and understanding of complex diseases whose etiology is currently unknown.
New Concepts of Pathogenesis in Inflammatory Bowel Disease
Authors: Fiocchi Claudio
Published: March 2016

The precise etiology and mechanisms of inflammatory bowel disease (IBD) are still unclear. Nevertheless, several concepts are gaining acceptance and constitute the basis for a better understanding of its pathogenesis and for improved therapy. The association of Crohn’s disease (CD) and ulcerative colitis (UC) with ‘western’ lifestyle is well recognized, and is considered a reason for the increasing frequency of CD and UC in countries with previously low incidence. Proposed linkages of CD and UC with particular human leukocyte antigen haplotypes suggest a genetic predisposition, but no uniform or consistent patterns have emerged. Similarly, the study of susceptibility or disease markers has not offered reproducible results. The search for specific infectious agents is being pursued, and the measles virus is presently considered a possible culprit. A true explosion has occurred in the area of animal models, and a large number of chemically or genetically induced experimental colitides are at hand. Immunological factors continue to dominate the bulk of basic research in IBD. This area is vast and complex, and autoantibodies, immune, epithelial and mesenchymal cells, lipid mediators, cytokines, neuropeptides and oxygen metabolites are under investigation. Finally, other factors whose role in IBD is uncertain, including smoking and possible abnormalities of intestinal permeability or mucus composition, continue to receive attention. These extensive and varied efforts are yielding some profits, and new forms of therapy are being devised. Based mostly on studies of soluble mediators, a number of novel immunosuppressive and highly specific blocking agents are being developed and undergoing clinical trials.
Spontaneous (Primary) Candida peritonitis
Authors: Sukhabote Joe , Freeman Hugh J
Published: March 2016

A 49‐year‐old female presented with abdominal pain and ascites. Subsequent investigations revealed Candida albicans in the ascitic fluid without evidence of systemic candidiasis or a source of local infection in another site. Additional studies revealed no evident underlying immunological disorder and the gastrointestinal tract was intact. Therapy with amphotericin B led to resolution of abdominal pain and ascites with no recurrence.
Intravenous Bolus versus Continuous Infusion of Famotidine or Ranitidine on 24 H Intragastric Acidity in Fasting Healthy Volunteers
Authors: Thomson ABR , Kirdeikis P , Wasarab-Rolland D , Zuk L , Pinchbeck B
Published: March 2016

Infusions of H2‐receptor antagonists may be clinically indicated to maintain intragastric pH above 4 to reduce acute gastric mucosal lesions or to treat patients with bleeding peptic ulcers. Eight fasting healthy volunteers were randomly assigned to receive ranitidine infusion alone (150 mg/day), ranitidine infusion plus 50 mg bolus injection of ranitidine (total of 200 mg/day), famotidine infusion alone (40 mg/day) or famotidine infusion plus 40 mg bolus injection of famotidine (total of 80 mg/day). Gastric fluid contents were aspirated for 24 h and collected as half‐hourly samples in which pH measurements were made. Measures analyzed were mean and median pH, percentage pH at or below 3, 4 or 5 for the 24 h period, daytime, evening and nighttime. The data for each of the variables were analyzed as a Latin square crossover design of variance therapy; base pH before treatment administration in each crossover phase was employed as the covariant. Significant differential treatment means were tested by Newman‐Keul’s multiple range test at the 5% level of significance. The mean and median evening pH were higher after famotidine than after ranitidine infusion, but all other pH readings were similar when using these doses. The addition of an initial loading bolus of 50 mg ranitidine to the ranitidine infusion did not result in any added differences in pH, whereas the addition of an initial loading bolus of 40 mg famotidine to the famotidine infusion resulted in a higher 24 h median pH, as well as a lower percentage of pH values of 4 or below, 16.6% versus 28.5%, P<0.05. However, the loading doses of ranitidine and famotidine were not equivalent in potency, and studies are needed to compare the potency of equivalent doses of ranitidine and famotidine when given by bolus plus infusion. Also the clinical relevance of these findings needs to be explored further in the type of individuals potentially requiring intravenous H2‐receptor antagonists.
Adherence of Helicobacter pylori to the Gastric Mucosa
Authors: Clyne Marguerite , Drumm Brendan
Published: March 2016

Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.
Use of Octreotide in the Acute Management of Bleeding Esophageal Varices
Authors: Sadowski Daniel C
Published: March 2016

Acute hemorrhage from esophageal varices is a medical emergency; despite early diagnosis and treatment the associated hospital mortality remains high. The clinical research summarized in this paper shows that octreotide has a beneficial effect on portal hemodynamics in cirrhotic patients. In randomized controlled trials octreotide has been effective in halting initial hemorrhage and in preventing reoccurrence of bleeding. Somatostatin and octreotide appear to be equivalent in terms of therapeutic efficacy but octreotide is the less expensive option. For suspected variceal bleeding an octreotide infusion should be initiated immediately. To prevent further bleeding the drug should be continued for two to five days after endoscopic variceal ligation.
A Suggested Approach to Patients with Dyspepsia
Authors: Thomson ABR
Published: March 2016

A comprehensive review of dyspepsia is presented. Topics include causes of dyspepsia, prevalence, causes of symptoms (motility abnormalities, visceral hypersensitivity, psychosocial aspects, role of Helicobacter pylori), investigations of patients with dyspepsia and, finally, whether there is effective treatment.
Evaluation of Salivary Antibodies to Detect Infection with Helicobacter pylori
Authors: Loeb Mark B , Riddell Robert H , James Cindy , Hunt Richard , Smaill Fiona M
Published: March 2016

Helicobacter pylori infection is an important cause of peptic ulcer disease and chronic gastritis. Infection with this bacterium stimulates the production of immunoglobulin (Ig) G antibody. Salivary IgG antibody tests to detect H pylori infection offer a convenient and noninvasive method of diagnosis. To evaluate an IgG salivary antibody kit, saliva was collected from 157 out-patients with dyspepsia referred for endoscopy to a tertiary centre. A salivary IgG ELISA antibody assay was performed using the Helisal Helicobacter pylori (IgG) assay kit, and at least four gastric biopsies were obtained. H pylori infection was confirmed by demonstration of the organism on Warthin-Starry silver stain (sensitivity 85%, specificity 55%). The prevalence of infection with H pylori was 30%. When the analysis was redone, excluding those treated with eradication therapy, the results were similar (sensitivity 86%, specificity 58%). The positive predictive value of the assay was 45% and the negative predictive value was 90%. Despite the ease of sampling, the assay used has limited diagnostic utility, lacking the predictive value to indicate which patients referred with dyspeptic symptoms to a tertiary care setting are infected with H pylori.
Endoscopists’ Opinions of Indications for Upper Gastrointestinal Endoscopy
Authors: Sutherland Lloyd R , Verhoef Marja J , Meddings Jonathan B , Bailey Robert J , Blustein Philip B , Lalor Eoin A , Thomson Alan BR , Rosendaal Guidomvan
Published: March 2016

OBJECTIVE:To determine whether endoscopists and general internistsagreed with the characterization of appropriatenessfor endoscopy of various clinical scenarios, as previouslyreported by the RAND Corporation.

DESIGN: Mail survey.

STUDY SAMPLE: All endoscopists in western Canadaand a random sample of general internists who did notperform endoscopy.

METHODS: Questionnaires were sent to 179 endoscopistsin western Canada who were asked to rate the 53 scenariosfor endoscopy on a nine‐point scale ranging from mostappropriate to most inappropriate. A similar questionnairewas sent to 39 general internists practising in theprovince of Alberta.

RESULTS: Response rate was 72% of endoscopists(n=128) and 64% of general internists (n=25). Amongthe endoscopists, there was agreement with the RANDclassification for 32 scenarios. All 18 indicationspreviously thought to be appropriate were consideredto be appropriate. However, endoscopists agreed withonly six of 16 equivocal and eight of 19 indicationsconsidered inappropriate. Discrepancies were reviewedby five experienced endoscopists and most appeared tobe related to a concern regarding possible malignancylinked in part with the definition of failure to respondto medical therapy; and to a refusal to request a bariummeal before endoscopy. Among general internists, therewas agreement with RAND in 26 scenarios. When the appropriatenessrankings of endoscopists and general internists werecompared, there was agreement in 40 of 53 scenarios.Significant discrepancies in ratings were identifiedin scenarios in which barium studies were describedas being normal, known or not done.

CONCLUSIONS: The equivocal and inappropriateratings developed by the RAND Corporation are not uniformlyaccepted by the endoscopy community or general internists.Use of the RAND indications for assessing quality assurancecan be challenged.