Role of Toll-like receptors in Helicobacter pylori infection and immunity

The gram-negative bacterium Helicobacter pylori(H. pylori) infects the stomachs of approximately half of the world's population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflamma-tory cells to the gastric mucosa. Pathogen recognition receptors of the toll-like receptor(TLR) family mediate many of these cell signalling events. This review dis-cusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic iden-tification of host mediators of H. pylori-induced patho-genesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy.

Rapunzel syndrome is not just a mere surgical problem: A case report and review of current management

Recurrent Rapunzel syndrome(RRS) is a rare clinical presentation with fewer than six cases reported in the Pub Med literature. A report of RRS and literature review is presented. A 25-year-old female was admitted to hospital with a 4-wk history of epigastric pain and swelling. She had a known history of trichophagia with a previous admission for Rapunzel syndrome requiring a laparotomy nine years earlier, aged 16. Psychological treatment had been successfully achieved for nine years with outpatient hypnotherapy sessions only, but she defaulted on her last session due to stressors at home. The abdominal examination demonstrated an epigastric mass. Computer tomography scan revealed a large gastric bezoar and features of aspiration pneumonia. The patient underwent emergency open surgical laparotomy for removal as the bezoar could not be removed endoscopically. The bezoar was cast in a shape that mimicked the contours of the stomach and proximal small bowel, hence the diagnosis of RRS. The patient was seen by a psychiatrist and was commenced on Quetiapine before discharge. She continues to attend follow-up.

Internet-based data inclusion in a population-based European collaborative follow-up study of inflammatory bowel disease patients: Description of methods used and analysis of factors influencing response rates

AIM： To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease （IBD） patients and to investigate the influence of demographic and disease related patient characteristics on response rates. METHODS： Thirteen years ago, the European Collaborative study group of IBD （EC-IBD） initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well- described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire （ePQ） and electronic physician per patient follow-up form （ePpPFU） were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression.total number of 1 505 （64%） available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion （OR： 1.53 （95% CI： 1.14-2.05）） and those with active disease during the 3 mo previous to ePQ completion （OR： 3.32 （95%CI： 1.57-7.03）） were significantly more likely to respond. CONCLUSION： An Internet-based data acquisition tool appeared successful in sustaining a unique Western- European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD.

Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance

The gram-negative bacterium Helicobacter pylori(H.pylori)causes chronic gastritis,gastric and duodenal ulcers,gastric cancer and mucosa-associated lymphoid tissue lymphoma.Treatment is recommended in all symptomatic patients.The current treatment options for H.pylori infection are outlined in this review in light of the recent challenges in eradication success,largely due to the rapid emergence of antibiotic resistant strains of H.pylori.Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H.pylori antibiotic resistance varies significantly from country to country,and even between regions within the same country.In addition,recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H.pylori.Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy.Antimicrobial resistance is assessed by H.pylori culture and antimicrobial susceptibility testing.Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H.pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material.Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H.pylori infection.

Role of Helicobacter pylori in functional dyspepsia

The aetiology of dyspepsia is unknown in the majority of patients. Helicobacter pylori （H pylon） is the cause in a subset of patients. A non invasive test to assess the presence of H pylori is recommended in the management of patients under the age of 50 presenting tO a family practitioner with dyspepsia. A urea breath test or a stool antigen test are the most reliable non invasive tests. Eradication of H pylori will reduce the risk to the patient with dyspepsia of developing a peptic ulcer, reduce the complication rate if prescribed nonsteroid anti-inflammatory drugs and later reduce the risk of gastric cancer. The recommended treatment for non ulcer dyspepsia associated with a H pylon infection should be a 10-d course of treatment with a PPI and two antibiotics. Treatment efficacy should be assessed four weeks after completing treatment with a urea breath test or a stool antigen test.

An update on the 2014 Ebola outbreak in western Africa

The recent Ebola outbreak in Western Africa was the most devastating outbreak witnessed in recent times,There have been remarkable local and international efforts to control the crisis,Ebola Virus Disease is the focus of immense research activity,The progression of events in the region has been evolving swiftly and it is of paramount importance to the medical community to be acquainted with the situation,Over 28 000 people were inflicted with the condition,over 11 000 have died,Novel data has emerged regarding modes of transmission,providing rationale for recent flare-ups,Similarly,studies on survivors are elucidating the later stages of the disease recovery process,Novel techniques for diagnosis are also discussed,Finally,the current research regarding treatment and vaccine development is reviewed,particularly the implementation of r VSV-ZEBOV vaccination programs.

Complications in the management of metastatic spinal disease

Metastatic spine disease accounts for 10% to 30% of new cancer diagnoses annually. The most frequent presentation is axial spinal pain. No treatment has been proven to increase the life expectancy of patients with spinal metastasis. The goals of therapy are pain control and functional preservation. The most important prognostic indicator for spinal metastases is the initial functional score. Treatment is multidisciplinary, and virtually all treatment is palliative. Management is guided by three key issues; neurologic compromise, spinal instability, and individual patient factors. Site-directed radiation, with or without chemotherapy is the most commonly used treatment modality for those patients presenting with spinal pain, causative by tumours which are not impinging on neural elements. Operative intervention has, until recently been advocated for establishing a tissue diagnosis, mechanical stabilization and for reduction of tumor burden but not for a curative approach. It is treatment of choice patients with diseaseadvancement despite radiotherapy and in those with known radiotherapy-resistant tumors. Vertebral resection and ante-rior stabilization with methacrylate or hardware(e.g., cages) has been advocated.Surgical decompression and stabilization, however, along with radiotherapy, may provide the most promising treatment. It stabilizes the metastatic deposited areaand allows ambulation with pain relief. In general, patients who are nonambulatory at diagnosis do poorly, as do patients in whom more than one vertebra is involved. Surgical intervention is indicated in patients with radiation-resistant tumors, spinal instability, spinal compression with bone or disk fragments, progressive neurologic deterioration, previous radiation exposure, and uncertain diagnosis that requires tissue diagnosis. The main goal in the management of spinal metastatic deposits is always palliative rather than curative, with the primary aim being pain relief and improved mobility. This however, does not come without complications, regardless of the surgical intervention technique used. These complication range from the general surgical complications of bleeding, infection, damage to surrounding structures and post operative DT/PE to spinal specific complications of persistent neurologic deficit and paralysis.

Functional oesophago-gastric junction imaging

Despite its role in disease there is still no definitive method to assess oesophago-gastric junction competence （OGJ）. Traditionally the OGJ has been assessed using manometry with lower oesophageal sphincter pressure as the indicator. More recently this has been shown not to be a very reliable marker of sphincter function and competence against reflux. Disorders such as gastro-oesophageal reflux disease and to a lesser extend achalasia still effects a significant number of patients. This review looks at using a new technique known as impedance planimetry to profile the geometry and pressure in the OGJ during distension of a bag. The data gathered can be reconstructed into a dynamic representation of OGJ action. This has been shown to provide a useful representation of the OGJ and to show changes to the competence of the OGJ in terms of compliance and distensibility as a result of endoluminal therapy.

BRAF inhibitor treatment of melanoma causing colonic polyps:An alternative hypothesis

Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with APC gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of MAPK genes. A minority of colorectal cancers develop by an alternative “serrated polyp pathway”. This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps. Serrated polyps are characterized by a CpG island methylation phenotype, MLH1 silencing and cellular senescence. They also have BRAF mutations. The contention is that BRAF inhibitor induced polyps mimic the afore-described histology and molecular features of serrated polyps with the exception that instead of the presence of BRAF mutations they induce C-RAF homodimers and B-RAF: C-RAF heterodimers.

Pill Cam COLON 2~? as a pan-enteroscopic test in Crohn's disease

A recent paper by Boal Carvalho et al demonstrates the potential of Pill Cam COLON 2?(PCC2) as a panenteric investigation in Crohn's disease(CD). Our own prospective data in patients with known CD also shows good correlation between PCC2 and small/large bowel investigations(R = 0.896,P < 0.0004/R = 0.6667,P <0.035). Larger studies are warranted to prospectively validate the use of PCC2 in the investigation and monitoring of both small and large bowel CD.

Computation of flow through the oesophagogastric junction

Whilst methods exist to indirectly measure the effects of increased flow or gastro-oesophageal refluxing, they cannot quantitatively measure the amount of acid travelling back up into the oesophagus during reflux, nor can they indicate the flow rate through the oesophagogastric junction (OGJ). Since OGJ dysfunction affects flow it seems most appropriate to describe the geometry of the OGJ and its effect on the flow. A device known as the functional lumen imaging probe (FLIP) has been shown to reliably measure the geometry of and pressure changes in the OGJ. FLIP cannot directly measure flow but the data gathered from the probe can be used to model flow through the junction by using computational flow dynamics (CFD). CFD uses a set of equations known as the Navier-Stokes equations to predict flow patterns and is a technique widely used in engineering. These equations are complex and require appropriate assumptions to provide simplifications before useful data can be obtained. With the assumption that the cross-sectional areas obtained via FLIP are circular, the radii of these circles can be obtained. A cubic interpolation scheme can then be applied to give a high-resolution geometry for the OGJ. In the case of modelling a reflux scenario, it can be seen that at the narrowest section a jet of fluid squirts into the oesophagus at a higher velocity than the fluid surrounding it. This jet has a maximum velocity of almost 2 ms-1 that occurs where the OGJ is at its narrowest. This simple prediction of acid ‘squirting’ into the oesophagusillustrates how the use of numerical methods can be used to develop a better understanding of the OGJ. This initial work using CFD shows some considerable promise for the future.

100 classic papers of interventional radiology: A citation analysis

AIM: To define the 100 citation classic papers of interventional radiology.METHODS: Using the database of Journal Citation Reports the 40 highest impact factor radiology journals were chosen. From these journals the 100 most cited interventional radiology papers were chosen and analysed.RESULTS: The top paper received 2497 citations and the 100 th paper 200 citations. The average number of citations was 320. Dates of publication ranged from 1953- 2005. Most papers originated in the United States(n = 67) followed by Italy(n = 20) and France(n = 10). Harvard University(n = 18) and Osped Civile(n = 11) were the most prolific institutions. Ten journals produced all of the top 100 papers with "Radiology" and "AJR" making up the majority. SN Goldberg and T Livraghi were the most prolific authors. Nearly two thirds of the papers(n = 61) were published after 1990.CONCLUSION: This analysis identifies many of the landmark interventional radiology papers and provides a fascinating insight into the changing discourse within the field. It also identifies topics, authors and institutions which have impacted greatly on the specialty.

Concept of chemoprevention in colorectal cancer

Colorectal cancer remains a significant cause of morbidity and mortality throughout the world.The incidence of colorectal cancer is nearly four-fold higher in more-developed as compared with less-developed regions of the world.At present an early detection of colorectal cancer remains a crucial step in determining the therapeutic outcomes.Screening programmes have been introduced in an effort to detect colorectal cancer at an early stage or at a precancerous colonic polyp stage.These programmes should be used by the health professionals as an opportunity to educate the public regarding the use of chemoprevention in colorectal cancer,which is the main focus of this review and an attractive concept needing further evaluation.

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature.We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke trial.Development of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were assessed.Analyses are adjusted for baseline prognostic factors and give OR and mean difference(MD)with 95%CI.Results In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;p<0.001).Nitrate-related headache was associated with:younger age,female sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(p<0.05).Nitrate headache was not associated with improved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,MD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,MD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or cognition.Discussion and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.