Aliment Pharmacol Ther 2010; 32: 573–581
Summary
Background The only therapy for coeliac disease (CD) is a long‐term gluten‐free diet (GFD). Little is known about the detailed composition of such a ...diet.
Aim To clarify the nutritional composition of a GFD and to compare it with a non‐GFD diet in representative non‐CD populations.
Methods A total of 139 consecutive patients with CD were invited to fill in a prospective validated 5‐day food diary, of whom data from 93 were analysed. Results were compared with data from the National Diet and Nutrition Survey of Adults and the UK Women’s Cohort Study (UKWCS).
Results Individuals consuming a strict GFD generally had similar intakes of energy and nutrients to those of comparison populations, but a higher proportion of carbohydrate intake was obtained from nonmilk extrinsic sugars and intakes of nonstarch polysaccharides were low. Compared with the UKWCS sample, female patients adhering to a GFD had lower intakes of magnesium, iron, zinc, manganese, selenium and folate. In male patients, intakes of magnesium and selenium were particularly low.
Conclusions This study reinforces the need for clinicians to recognize that avoidance of gluten cannot be the sole focus of a gluten‐free diet. Maintenance of adequate intakes of essential nutrients and in particular complex carbohydrates must also be the goal for patients.
To describe the incidence and nature of neurologic complications following liver transplantation.
Adult patients who received liver transplants at St. James's University Hospital between September 1, ...1990, and August 31, 2000, were identified. Case notes were reviewed and demographic data, details of the liver disease, neurologic complications, and discharge information were recorded.
The authors identified 657 patients and traced the case notes of 627 (95.4%). These patients had a total of 711 transplants. Neurologic complications occurred following 185 transplants (26%) affecting 170 patients (27%). The most common complications were diffuse encephalopathies, which affected 66 patients (11%), and seizures, which affected 37 patients (6%). Forty-three percent of patients with alcoholic liver disease and 41% of patients with primary biliary cirrhosis experienced a neurologic complication. These proportions were higher than for other transplant indications (p < 0.001). Patients who experienced a neurologic problem spent longer in hospital (p < 0.01) and had a poorer outcome (p < 0.001).
Neurologic complications occur following 26% of liver transplants. A higher proportion of patients who received transplants for alcoholic liver disease and primary biliary cirrhosis experienced neurologic complications than those receiving transplants for other reasons. Patients who experience a neurologic problem spend longer in hospital and have a poorer outcome.
Background: Malignancies of the small intestine are rare, accounting for <2% of all cancers of the gastrointestinal tract. There is little information about the presentation and prognosis of these ...tumours, and the frequency of established risk factors. Aim: To estimate the frequency of small‐bowel malignancy in the UK, and its relationship to the presence of coeliac disease. Design: Survey of clinicians registered with the British Society of Gastroenterology. Methods: Data were collected monthly from June 1998 to May 2000. Clinicians (n=1327) were asked by post to report newly diagnosed cases of primary small‐bowel malignancy. A form was sent to reporting clinicians, requesting an anonymous identifier, type of malignancy, and whether coeliac disease was present. A detailed questionnaire followed, requesting further clinical and pathological details. Results: Clinico‐pathological data were ascertained for 395 cases, including 175 adenocarcinomas, 107 lymphomas and 79 carcinoid tumours. In 13% of adenocarcinoma cases and in 39% of lymphomas, there was a diagnosis of coeliac disease. Survival rates at 30 months for adenocarcinomas, lymphomas and carcinoid tumours were 58%, 45% and 78%, respectively. Prognosis of all tumours was inversely related to stage at presentation, and lymphomas associated with coeliac disease were associated with a poorer prognosis. Discussion: This study provides additional evidence that coeliac disease confers susceptibility to adenocarcinoma of the small bowel, as well as lymphoma. The long time from the onset of symptoms to diagnosis of small bowel tumours is of concern, as this delay is reflected in the high proportion that presented with metastatic disease. Although the absolute risk of malignancy is small, coeliac disease complicated by malignancy appears to be poorly controlled.
A thermal desorption unit has been interfaced to an electrospray ionization-ion mobility-time-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic ...compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L−1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other. The combination of temperature programmed thermal desorption and ion mobility improved the response of selected species against background ions. Analysis of breath samples resulted in the identification of breath metabolites, based on ion mobility and accurate mass measurement using siloxane peaks identified during the analysis as internal lockmasses.
Small bowel adenocarcinoma (SBA) is a rare cancer and consequently, the options for clinical trials are limited. As they are treated according to either a colorectal or a gastric cancer regimen and ...the molecular biology of a tumor is a pivotal determinant for therapy response, chromosomal copy number aberrations were compared with the colorectal and gastric adenocarcinomas.
A total of 85 microsatellite stable (MSS) adenocarcinomas from the stomach, colorectum and small bowel were selected from existing array comparative genomic hybridization (aCGH) datasets. We compared the aCGH profiles of the three tumor sites by supervised analysis and hierarchical clustering.
Hierarchical clustering revealed substantial overlap of 27 SBA copy number profiles with matched colorectal adenocarcinomas but less overlap with profiles of gastric adenocarcinomas. DNA copy number aberrations located at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1, 13q13.2-q31.3 and 17p13.3-p13.2 were the strongest features discriminating SBAs and colorectal adenocarcinomas from gastric adenocarcinomas.
We show that MSS SBAs are more similar to colorectal than to gastric cancer, based on the 27 genome-wide DNA copy number profiles that are currently available. These molecular similarities provide added support for treatment of MSS small bowel cancers according to colorectal cancer regimens.
Background: Coeliac disease is a relatively common condition which is usually managed by placing patients on a gluten free diet. Follow up biopsies to confirm histological recovery are controversial ...with a considerable variation in practice observed. Aim: To determine the length of time to histopathological recovery in a group of coeliac disease patients and its associations with clinicopathological data. Design and methods: All patients attending a specialist coeliac disease clinic prior to March 2009 were entered onto a database which recorded various clinicopathological data. The histopathology reports for all duodenal biopsies were reviewed and each biopsy was given a histopathological disease score based on a modified Marsh grade. Results: Two hundred and eighty-four patients underwent index and at least one subsequent biopsy. Two-hundred and twenty-seven (80%) showed histopathological improvement and 100 (35%) returned to normal (median recovery time 1.9 years, inter-quartile range 1.0–4.8 years). Patients with less severe disease at diagnosis were more likely to show a better response (r = 0.281, P < 0.0001). Older patients demonstrated a shorter time to histopathological recovery (r = −0.200, P = 0.001). Compliance with a gluten free diet was correlated with the best biopsy score (r = −0.134, P = 0.040) and degree of histological recovery (r = 0.161, P = 0.014). Conclusions: Current guidelines for the timing of repeat biopsy after commencing a gluten free diet are unclear, although 4–6 months has been recommended. This study shows that time to histological recovery is longer than traditionally thought and may need to take into account the patient’s age at diagnosis, the initial disease score and the level of compliance with a gluten free diet.
To determine antioxidant vitamin concentrations, lipid peroxidation, and an index of nitric oxide production in patients in the intensive care unit (ICU) with septic shock and relate the findings to ...the presence of secondary organ failure.
A prospective, observational study.
A nine-bed ICU in a University teaching hospital.
Sixteen consecutive patients with septic shock, defined as: a) clinical evidence of acute infection; b) hypo- or hyperthermia (< 35.6 degrees C or > 38.3 degrees C); c) tachypnea (> 20 breaths/min or being mechanically ventilated); d) tachycardia (> 90 beats/min); e) shock (systolic pressure < 90 mm Hg) or receiving inotropes. Fourteen patients also had secondary organ dysfunction.
None.
Antioxidant vitamin concentrations were significantly lower in the patients than the reference range obtained from a comparable group of healthy controls. The mean plasma retinol (vitamin A) concentration was 26.5 +/- 19.3 micrograms/dL compared with 73.5 +/- 18.3 micrograms/dL in healthy subjects (p < .01). Additionally, 13 (81%) patients had retinol values below the lower limit of our reference range (< 37.0 micrograms/dL). Tocopherol (vitamin E) plasma concentrations were below the reference range in all patients (< 9.0 mg/L), with a mean value of 3.6 +/- 2.0 mg/L compared with 11.5 +/- 1.3 mg/L in healthy subjects (p < .001). Plasma beta carotene and lycopene concentrations were undetectable (< 15 micrograms/L) in eight (50%) patients, and below our reference range (< 101 micrograms/L and < 154 micrograms/L, respectively) in the remaining patients. In the five patients with three or more dysfunctional secondary organs, plasma thiobarbituric acid-reactive substances were significantly increased (p < .05), suggesting increased lipid peroxidation. Concentrations of thiobarbituric acid-reactive substances correlated negatively with both plasma retinol and plasma tocopherol (r2 = .42, p < .01 and r2 = .48, p < .005, respectively). In the five patients from whom we were able to collect urine, nitrite excretion was increased approximately 400-fold (p < .001).
These data indicate decreased antioxidant status in the face of enhanced free radical activity, and suggest potential therapeutic strategies involving antioxidant repletion.
Background: A raised intraepithelial lymphocyte (IEL) count with normal villous architecture is a recognised finding in latent coeliac disease. Little information is available in cases without gluten ...sensitive enteropathy in adults. Aims: To assess the frequency of such a finding in routine practice and to determine whether it is clinically relevant. Methods: Patients with subjectively increased IELs as the only abnormality were identified prospectively from a routine duodenal biopsy series over a 12 month period. The biopsy specimens in these index cases were re-examined together with two controls with normal histology for each case, and three counts of IEL/100 epithelial cells were made in all samples. The index cases were then contacted and interviewed to obtain clinical information, approximately 12 months from the initial biopsy. Further data were obtained from their clinical records. Results: Fourteen of 626 (2.2%) patients who had duodenal biopsies over the 12 month period had a subjective increase in IELs with normal villous architecture. Fifteen patients with newly diagnosed gluten sensitive enteropathy were also identified during the study period. Formal counting of the index cases and controls revealed a significant difference in IELs/100 epithelial cell counts between the two (mean, 38 (SD, 6.2) v 12.4 (4.6); p < 0.0001). Three of the 14 index cases tested had a positive coeliac antibody test compared with 12 of 15 newly diagnosed patients with coeliac disease and 10 of 93 patients with normal histology. The major clinical diagnostic categories in raised IEL cases were those with positive coeliac serology (n = 3), unexplained anaemia (n = 3), and chronic liver disease (n = 3). Six of 10 patients who were interviewed had ongoing gastrointestinal symptoms one year later. Three patients had had follow up duodenal biopsies, at the discretion of their responsible clinicians, with no change in IEL counts despite the commencement of a gluten free diet in two patients. Conclusion: A raised IEL count with normal villous architecture is not uncommon. Six of the 14 patients may have had latent coeliac disease. The cause in at least half of cases is not obvious at present. The finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be highlighted in routine duodenal biopsy reports.
AIM： To investigate the function of NOD2 in colonic epithelial cells （CEC）. METHODS： A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a ...functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS： In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide （MDP）, that is recognized by NOD2, promoted CEC growth in vitro. By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2^-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION： These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation.
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