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Background: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors.Methods: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012-2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded.Results: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20-0.60 95% CI and 0.47; 0.25-0.88, respectively).Conclusion: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur. [ABSTRACT FROM AUTHOR]

With continued efforts to find solutions to rising rates of obesity and diabetes, there is increased interest in the potential health benefits of the use of low- and nocalorie sweeteners (LNCSs). Concerns about safety often deter the use of LNCSs as a tool in helping control caloric intake, even though the safety of LNCS use has been affirmed by regulatory agencies worldwide. In many cases, an understanding of the biological fate of the different LNSCs can help health professionals to address safety concerns. The objectives of this review are to compare the similarities and differences in the chemistry, regulatory status, and biological fate (including absorption, distribution, metabolism, and excretion) of the commonly used LNCSs: acesulfame potassium, aspartame, saccharin, stevia leaf extract (steviol glycoside), and sucralose. Understanding the biological fate of the different LNCSs is helpful in evaluating whether reports of biological effects in animal studies or in humans are indicative of possible safety concerns. Illustrations of the usefulness of this information to address questions about LNCSs include discussion of systemic exposure to LNCSs, the use of sweetener combinations, and the potential for effects of LNCSs on the gut microflora. [ABSTRACT FROM AUTHOR]

Background: Traditional journal club models based on didactic presentation sessions followed by group discussion have many limitations. To overcome some of these shortcomings, a virtual journal club (VJC) using social media and e-mail was developed. The aim of this study was to report the initial experience of this novel multimodal e-learning platform to facilitate journal club discussion and promote the development of critical appraisal skills. Methods: Journal articles were discussed monthly via e-mail and social media. After a 3-week period of discussion, all comments were collated and groupgenerated critical appraisal summaries were fed back to participants. In addition, letters to the journal editors based on the group appraisal were submitted. A questionnaire survey to evaluate the VJC concept was also conducted. Findings: After eight cycles of the VJC, the mean trainee participation rate was 29.6 per cent (range 21.1-42.1%). Senior trainees (≥4 years of postgraduate experience) were more likely to participate than more junior trainees (75.0 versus 21.1%; p = 0.005). The majority of participants thought that the VJC was educationally valuable, easy to participate in, helpful in keeping up to date with recent papers and useful in developing critical appraisal skills. Barriers to participation were lack of time, motivation and lack of experience in critical appraisal. In addition, the group- generated critical appraisal summaries derived from VJC discussions led to eight published 'letters to the editor'. Conclusion: This novel VJC model is a feasible and popular method of delivering a journal club in the postgraduate setting. [ABSTRACT FROM AUTHOR]

The present review explores the interactions between sweeteners and enteroendocrine cells, and consequences for glucose absorption and insulin release. A combination of in vitro,in situ, molecular biology and clinical studies has formed the basis of our knowledge about the taste receptor proteins in the glucose-sensing enteroendocrine cells and the secretion of incretins by these cells. Low-energy (intense) sweeteners have been used as tools to define the role of intestinal sweet-taste receptors in glucose absorption. Recent studies using animal and human cell lines and knockout mice have shown that low-energy sweeteners can stimulate intestinal enteroendocrine cells to release glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. These studies have given rise to major speculations that the ingestion of food and beverages containing low-energy sweeteners may act via these intestinal mechanisms to increase obesity and the metabolic syndrome due to a loss of equilibrium between taste receptor activation, nutrient assimilation and appetite. However, data from numerous publications on the effects of low-energy sweeteners on appetite, insulin and glucose levels, food intake and body weight have shown that there is no consistent evidence that low-energy sweeteners increase appetite or subsequent food intake, cause insulin release or affect blood pressure in normal subjects. Thus, the data from extensive in vivo studies in human subjects show that low-energy sweeteners do not have any of the adverse effects predicted by in vitro,in situ or knockout studies in animals. [ABSTRACT FROM PUBLISHER]

At the present time the recommended daily intake or allowance (RDA) and the safe upper level (UL) of intake of micronutrients are given as single values. The recommended daily intake is considered to cover the requirements of 97.5% of the population while the safe upper level is a value for the whole population. These values provide only limited guidance to risk managers. A method has been developed recently which models the relationships between intake and risks of either deficiency or excess using an observed incidence for each effect and population distribution characteristics. Using this model it is possible to formulate advice to risk managers on the incidence (prevalence) of adverse effects, due to either deficiency or excess, at different levels of intake. Application of the model to the data used to derive the RDA and UL for selenium shows that it can predict the impact of changes in nutrient intake on the balance between benefit (absence of deficiency) and risk (development of toxicity). Application of the model has illustrated the utility of this approach, but highlighted the need for a comprehensive evaluation of the data and a critical appraisal of the validity of the relationships that are analyzed. In addition, the derived incidences will usually relate to effects with different biological or health impacts, so that the final balance between benefit and risk should be developed by a dialogue between the risk assessor and the risk manager. [ABSTRACT FROM AUTHOR]

Patients with perineal burns and immobile hospitalized patients with severe excoriation from incontinence caused by excessive diarrhea pose difficult management problems, frequently requiring stoma formation. The Zassi Bowel Management System (Zassi Medical Evolutions, Fernandina Beach, Florida) multichannel intrarectal catheter was evaluated for its safety and its ability to divert feces away from perineal skin to allow wound and skin healing. A prospective cohort study was conducted on inpatients from the Burns and Geriatric Units. Patients with previous rectal disease were excluded. Perineal skin and wound healing was measured before and after tube insertion by using the perianal disease activity index score. Data regarding patient comfort, wound contamination, dressing changes, bed linen changes, and adverse events were collected. Proctoscopy was performed before and after tube insertion. Twenty-two tubes were inserted in 20 patients (7 perineal burns, 13 severe perineal excoriations). Mean perianal disease activity index scores reduced from 14 to 6.4 ( P < 0.0001) after tube insertion. Mean dressing changes reduced from 3.3 to 1.5 times per day ( P < 0.01), and mean bed linen changes in the incontinent patients reduced from 9.3 to 1.2 times per day ( P < 0.0001). Mean duration of rectal intubation was 14 days. Proctoscopy after tube removal was normal in all cases. One patient developed a superficial ulcer on the buttock from retention strapping. The Zassi Bowel Management System tube allows diversion of feces away from the perineum for wound healing. It is safe, effective, and may help avoid stoma formation. [ABSTRACT FROM AUTHOR]

Studies on the intakes of intense sweeteners in different countries published since the author's previous review in 1999 indicate that the average and 95th percentile intakes of acesulfame-K, aspartame, cyclamate and saccharin by adults are below the relevant acceptable daily intake (ADI) values. Fewer data are available for the newer sweeteners, sucralose and alitame, and because they are recent introductions to the market very low intakes were reported in those countries where they were available at the time of the intake study. Overall there has not been a significant change in the intakes of sweeteners in recent years. The only data indicating that the intake of an intense sweetener could exceed its ADI value were the 95th percentile intakes of cyclamate in children, particularly those with diabetes. This sub-group was identified as having high intakes of cyclamate in 1999, and recent studies have not generated reliable intake data to address this possibility. [ABSTRACT FROM AUTHOR]

Focuses on the topics discussed during the session 3 of the general discussion at the Fourth Workshop on the Assessment of Adequate Intake of Dietary Amino Acids in Kobe-shi, Japan on October 28-29, 2004. Risk assessment on the dosage of branched-chain amino acids; Adverse effects of amino acids; Pharmacokinetics of branched-chain metabolites.

The safety assessment of high intake levels of individual amino acids cannot be based on data from nutritional studies with proteins. Routine toxicity tests designed to investigate a wide range of possible effects should be undertaken for hazard identification and characterization using studies selected to mirror the predicted pattern and duration of human exposure. The approach used to establish an acceptable daily intake level for additives and pesticides, based on defining a "no observed adverse effect" level in the experimental study and dividing by uncertainty factors that allow for species differences and human variability, has a long history of use for foreign compounds and would provide a suitable basis for determining health-based guidance values for single amino acids. The usual default uncertainty factors for toxicokinetics and toxicodynamics should be replaced by compound-specific values if suitable data are available. In addition, the usual uncertainty factors should be modified to more relevant default values based on species differences and human variability in the biodisposition of amino acids in general or of groups of metabolically interrelated amino acids. There would be no significant health concerns if the human intake levels were below a health-based guidance value developed using this approach. A population-distribution approach could be used to define the magnitude of any risk at intake levels above the guidance value. [ABSTRACT FROM AUTHOR]

Focuses on the residue levels of pesticides used for agricultural purpose in human food, and on the procedures that are in place in the United Kingdom to ensure that human exposure does not result in significant adverse health effects. Major steps of the risk assessment paradigm of chemicals; Influence of the nature of the hazard on the risk assessment procedure adopted; Risk assessment for food additives; Main toxicity tests for hazard identification in animals.

This manuscript addresses the content of and considerations in the implementation of guidance in the use of kinetic and dynamic data to inform quantitatively extrapolations for inter-species differences and human variability in dose response assessment developed in a project of the International Programme on Chemical Safety (IPCS) initiative on Harmonisation of Approaches to the Assessment of Risk from Exposure to Chemicals. The guidance has been developed and refined through a series of planning and technical meetings and larger workshops of a broad range of participants from academia, government agencies and the private sector. The guidance for adequacy of data for replacement of defaults for interspecies differences and human variability commonly adopted in the derivation of Tolerable or Acceptable Intakes is presented principally through illustrative reference to case examples. The relevant guidance is addressed in the context of several generic categories, including determination of the active chemical species, choice of the appropriate kinetic parameter or endpoint (dynamic component) and nature of experimental data, the latter, which includes reference to the relevance of population, route and dose and the adequacy of the number of subjects/samples. [ABSTRACT FROM AUTHOR]

For the risk to human health posed by chemicals that show threshold toxicity there is an increasing need to move away from using the default approaches, which inherently incorporate uncertainty, towards more biologically defensible risk assessments. However, most chemical databases do not contain data of sufficient quantity or quality that can be used to replace either the interspecies or interindividual aspects of toxicokinetic and toxicodynamic uncertainty. The purpose of the current analysis was to evaluate the use of alternative, species-specific, pathway-related, "categorical" default values to replace the current interspecies toxicokinetic default uncertainty factor of 4.0. The extent of the difference in the internal dose of a compound, for each test species, could then be related to the specific route of metabolism in humans. This refinement would allow for different categories of defaults to be used, providing that the metabolic fate of a toxicant was known in humans. Interspecies differences in metabolism, excretion, and bioavailability have been compared for probe substrates for four different human xenobiotic-metabolizing enzymes: CYP1A2 (caffeine, paraxanthine, theobromine, and theophylline), CYP3A4 (lidocaine), UDP-glucuronyltransferase (AZT), and esterases (aspirin). The results of this analysis showed that there are significant differences between humans and the four test species in the metabolic fate of the probe compounds, the enzymes involved, the route of excretion and oral bioavailability — all of which are factors that can influence the extent of the difference between humans and a test species in the internal dose of a toxicant. The wide variability between both compounds and the individual species suggests that the categorical approach for species differences may be of limited use in refining the current default approach. However, future work to incorporate a wider database of compounds that are metabolized extensively by any... [ABSTRACT FROM AUTHOR]

The default uncertainty factors used for risk assessment are applied either to allow for different aspects of extrapolation of the dose-response curve or to allow for database deficiencies. Replacement of toxicokinetic or toxicodynamics defaults by chemical-specific data allows the calculation of a chemical-specific "data-derived factor", which is the product of chemical-specific values and default uncertainty factors. Such chemical-specific composite values will improve the scientific basis of the risk assessment of that chemical, but the necessary chemical-specific data are rarely available. Categorical defaults related to pathways of elimination and mechanisms of toxicity could be used when the overall fate or mechanism is known, but there are no chemical-specific data sufficient to allow replacement of the default, and the development of an overall data-derived factor. The development of pathway-related categorical defaults is being undertaken using data on selected probe substrates for which adequate data are available. The concept and difficulties of this approach are illustrated using data for CYP1A2. [ABSTRACT FROM AUTHOR]

Describes the case of a schizophrenic patient who lost consciousness due to an overdose of clozapine. Case report; Treatment methodology; Results and discussion.

Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3-to 4-fold higher in rats than in humans and data on dynamic differences—in order to modify the default value—are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation. [ABSTRACT FROM AUTHOR]

Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3-to 4-fold higher in rats than in humans and data on dynamic differences—in order to modify the default value—are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation. [ABSTRACT FROM AUTHOR]

With a low incidence of Salmonella infection, salmonellosis is an uncommon problem in Scotland. It occurs in both immune-compromised and immune-competent patients. We present two cases of salmonellosis in immune-competent patients who had had a history of gastroenteritis. Diagnosis was delayed in one patient; however, both patients received appropriate treatment and made good recovery following their respective illnesses. Apart from acting as a reminder to consider salmonellosis as a differential diagnosis when managing patients with infective process, the cases also highlight the importance of concise history taking, and the importance of cultures-andsensitivities in managing infectious cases. [ABSTRACT FROM AUTHOR]

Extensive discussion sessions were held at the end of each of the 2 d of the workshop. Through the course of the workshop, it became clear that there were different opinions on how to use uncertainty factors to obtain upper levels of intake from no observed adverse effect levels of a particular nutrient and that the selection of an appropriate uncertainty factor would be rather arbitrary. Much of the discussion centered around the potential for using metabolic limits, expressed as the level of intake at which the major pathway of metabolism may approach saturation and at which the amino acid is metabolized by alternative pathways, as a measurable early or surrogate marker for amino acid excess and possible toxicity. After extensive discussion on various conditions that would need to be satisfied for metabolic limits to be used as markers of excessive intake of amino acids, there was a general consensus that methods such as measuring oxidation limits are an attractive approach that merit future investigation, It was noted that there are many data on the clinical use of glutamine, whereas data for proline are very scarce. There was recognition that regardless of the available data, there is regulatory pressure for setting upper levels of intake for amino acids and that much more data are required. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a workshop on the assessment of adequate intake of dietary amino acids is presented. The discussion centered on the problems raised in relation to setting a safe upper levels for sulfur-containing amino acids. Speakers have argued that in order to set a safe upper levels, it is essential to integrate data from a different sources including metabolic data, data from analysis in humans and data on inborn errors of metabolism.

Explores the risk assessment methods for amino acids. Development of biomarkers; Application of the high-resolution nuclear magnetic resonance spectroscopy.

Over a 38-month period, prospective data were collected on all episodes of intussusception treated at the Royal Children's Hospital, Melbourne. There were 170 initial episodes for which a gas enema was performed, 127 of which were reduced successfully. Recurence occured in 10 patients following initial successful gas enema reduction, a recurrence rate of 7.9%, which compares with a recurrence rate of 8.9% with barium ( P = 0.896). We conclude that the gas enema does not have a higher rate of recurrence than barium and that there is no evidence of a significant incidence of incomplete reduction unrecognised at the time of gas enema. [ABSTRACT FROM AUTHOR]

Based on recent research, an upper limit of safe intake (ULSI) for leucine is proposed for healthy adults: 0.53 g/(kg-d). Because leucine has been used as a dietary supplement for many years in people practicing exercise and sport, further study with long-term exposure to leucine in this specific subpopulation should be performed to eventually adjust the ULSI. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a symposium on the assessment of adequate intake of dietary amino acids is presented. Participants with toxicological and regulatory backgrounds commented on the paucity of the adverse effects of many micronutrients. The identification of metabolic limits for arginine or lysine excess was also recognized.

Presents a letter to the editor on chronic non-healing anal ulceration and Nicorandil.

A letter to the editor is presented in response to the 2014 article in issue 36 of the journal entitled "The use of mini-CEX in UK foundation training six years following its introduction: Lessons still to be learned and the benefit of formal teaching regarding utility" by PSJ Weston and CA Smith.

A letter to the editor is presented in response to the article "Printed quit-pack sent to surgical patients at time of waiting list placement improved perioperative quitting," by A.R. Webb et al., published in this issue of the journal.