When perforation is not the culprit : case report and systematic review of mechanical small-bowel obstruction complicating colonoscopy.

Colonoscopy is generally safe, although expansion of colorectal cancer prevention programs is likely to increase the number of post-colonoscopy complications. We report the case of a 42-year old woman with a prior history of 2 cesarean section deliveries who developed abdominal pain after an otherwise uneventful screening colonoscopy. Urgent exploration revealed closed-loop obstruction involving the terminal ileum, caused by an adhesive band close to the site of her previous Pfannenstiel incision. A systematic review of the literature revealed 11 reports (1985-2008) describing a total of 13 cases of mechanical small bowel obstruction (MSBO) after colonoscopy, 9 of which were confirmed by laparotomy. Colonoscopy-induced MSBO is practically impossible to anticipate, and only a prior history of abdominal/pelvic surgery may be deemed as a predisposing factor. However, it is related to significant morbidity, as it often leads to an ischemic bowel with need for surgical resection. Thus, endoscopists should be aware and maintain a low operative threshold to this rare, but hazardous, complication of colonoscopy.

Preliminary diagnostic reference levels for endoscopic retrograde cholangio-pancreatography in Greece.

The main objective of this study was to determine the preliminary Diagnostic Reference Levels (DRLs) in terms of Kerma Area Product (KAP) and fluoroscopy time (Tf) during Endoscopic Retrograde Cholangio-Pancreatography (ERCP) procedures. Additionally, an investigation was conducted to explore the statistical relation between KAP and Tf. Data from a set of 200 randomly selected patients treated in 4 large hospitals in Greece (50 patients per hospital) were analyzed in order to obtain preliminary DRLs for KAP and Tf during therapeutic ERCP procedures. Non-parametric statistic tests were performed in order to determine a statistically significant relation between KAP and Tf. The resulting third quartiles for KAP and Tf for hospitals (A, B, C and D) were found as followed: KAPA=10.7Gycm(2), TfA=4.9min; KAPB=7.5Gycm(2), TfB=5.0min; KAPC=19.0Gycm(2), TfC=7.3min; KAPD=52.4Gycm(2), TfD=15.8min. The third quartiles, calculated for the total 200 cases sample, are: KAP=18.8Gycm(2) and Tf=8.2min. For 3 out of 4 hospitals and for the total sample, p-values of statistical indices (correlation of KAP and Tf) are less than 0.001, while for the Hospital A p-values are ranging from 0.07 to 0.08. Using curve fitting, we finally determine that the relation of Tf and KAP is deriving from a power equation (KAP=Tf(1.282)) with R(2)=0.85. The suggested Preliminary DRLs (deriving from the third quartiles of the total sample) for Greece are: KAP=19Gycm(2) and Tf=8min, while the relation between KAP and Tf is efficiently described by a power equation.

Patient and endoscopist radiation doses during ERCP procedures.

The aim of the study was to calculate radiation doses for patients and staff during interventional Endoscopic retrograde cholangiopancreatography (ERCP) procedures. Patient age (A), kerma-area product (KAP), fluoroscopy time (T) and total number of films (F) were collected for 157 interventional ERCP procedures. One endoscopist (>10 y of experience) monitored using a thermoluminescent dosemeter worn over the lead apron performed the ERCPs. Median (range) KAP was 3.1 Gy cm(-2) (0.1-106.7 Gy cm(-2)). Median (range) A, T and F were 72 y, 2.6 (0.2-26.0) min and 2 (1-4) images, respectively. No correlation was observed between KAP and A, T or F. Monthly endoscopist dose was negligible due to the use of lead apron, collar and two lead-articulated ceiling mounted shields. The endoscopist dose is minimal when using appropriate protective measures. Patient doses showed large variation that has to be further investigated.

Similar response to adalimumab in patients with active Crohn's disease either naive to biologic agents or with prior loss of response or intolerance to infliximab.

UNLABELLED: The aim of this study was to investigate the efficacy of adalimumab, in patients with moderately active Crohn's disease (CD), either naive to biologic agents or with prior loss of response or intolerance to infliximab. MATERIAL AND METHOD: A total number of 30 patients with moderately active CD (14 men, 16 women, aged 38.5 +/- 14.4 yr) either naive to biologic agent treatment (19 pts (65%)) or with loss of response or intolerance to infliximab (11 pts (35%)), were enrolled to 4-wk trial with treatment with subcutaneous adalimumab 160 mg injection at week 0, 80 mg at week 2 and then 40 mg every other week. Outcome measures included the ability to tolerate adalimumab and clinical remission (defined as a CDAI score < or =150 points) and clinical response (defined as a decrease in the CDAI) > or =70 points). Eleven patients (37%) were smokers, 5(16%) ex-smokers and 14 (47%) non-smokers. Five patients (16%) had a positive family history for IBD. Duration of disease was 10.7 +/- 8.1 yr. Coexistence of extraintestinal manifestations was noticed in 12 (40%) patients. Vienna Classification of CD was A1=24 (80%), A2=6 (20%), L1=8 (26.7%), L2=6 (20%), L3=15 (50%), L4=1 (3.3%), B1=15 (50%), B2=5 (16.7%), B3=10 (33.3%). RESULTS: Remission was observed in 19 (63.3%) and clinical response in 9 (30%) patients. Two patients (6.7%) showed no response. No significant differences between patients with loss of response or intolerance to infliximab and the group of naive patients were noticed. Comparison between smokers and non smokers revealed significant difference in the response rate in favour of non-smokers (P < 0.002). A trend (P = 0.064) towards a significant difference in the response rate of the group of smokers according to the number of cigarettes smoked per day was observed. Patients with short duration of disease (<10 yr) had significantly better response compared to the group of patients with long (>10 yr) duration of disease. Similarly, patients with extraintestinal manifestations showed significantly better response (P = 0.044). None of the patients in both groups experienced acute or delayed hypersensitivity reactions during treatment with adalimumab. CONCLUSION: Adalimumab is well tolerated and appears to be a beneficial option for patients with CD who have not previously treated with biologic agents or have lost their response to, or cannot tolerate infliximab, with non-smokers, patients with short duration of CD, and patients with extraintestinal manifestations having a better clinical response.

Sedation in digestive endoscopy: the Athens international position statements.

BACKGROUND: Guidelines and practice standards for sedation in endoscopy have been developed by various national professional societies. No attempt has been made to assess consensus among internationally recognized experts in this field. AIM: To identify areas of consensus and dissent among international experts on a broad range of issues pertaining to the practice of sedation in digestive endoscopy. METHODS: Thirty-two position statements were reviewed during a 1 (1/2)-day meeting. Thirty-two individuals from 12 countries and four continents, representing the fields of gastroenterology, anaesthesiology and medical jurisprudence heard evidence-based presentations on each statement. Level of agreement among the experts for each statement was determined by an open poll. RESULTS: The principle recommendations included the following: (i) sedation improves patient tolerance and compliance for endoscopy, (ii) whenever possible, patients undergoing endoscopy should be offered the option of having the procedure either with or without sedation, (iii) monitoring of vital signs as well as the levels of consciousness and pain/discomfort should be performed routinely during endoscopy, and (iv) endoscopists and nurses with appropriate training can safely and effectively administer propofol to low-risk patients undergoing endoscopic procedures. CONCLUSIONS: While the standards of practice vary from country to country, there was broad agreement among participants regarding most issues pertaining to sedation during endoscopy.

Recommendations to improve identification of hereditary and familial colorectal cancer in Europe.

Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.

Expression of Bax protein in gastric carcinomas. A clinicopathological and immunohistochemical study.

BACKGROUND AND STUDY AIMS: Reduced Bax protein expression has been shown to be a negative prognostic factor in patients with breast, ovarian, colorectal, esophageal and pancreatic cancer. Our aim was to immunohistochemically study Bax protein expression in gastric carcinomas and correlate its expression with clinicopathological parameters and prognosis. PATIENTS AND METHODS: Immunohistochemistry was performed, using a monoclonal antibody against bax, in paraffin-embedded tumor specimens from 47 cases of gastric cancer. RESULTS: Positive staining for the Bax protein was found in 20/47 (42.4%) adenocarcinomas examined. Negative Bax protein expression in tumour cells was correlated with lymph node metastasis (P < 0.05), and degree of differentiation (p < 0.05). Univariate analysis showed that the variables with a significant negative impact on survival were: high TNM tumour stage, depth of penetration in the gastric wall, lymph node involvement, and Bax protein expression. Multivariate analysis showed that the only variable with an impact on survival was Bax protein expression (p < 0.05, Relative Risk: 3.34). Kaplan-Meier curves showed that the 5-year survival was 36.8% in cases with positive compared with 16% in cases with negative Bax protein expression (p = 0.0427). CONCLUSION: Negative Bax expression in gastric cancer is associated with de-differentiation, lymph node metastases, and poor clinical prognosis. Bax protein expression might play an important role in the development and phenotypic differentiation of gastric carcinomas and tumor progression.

Radiation doses to patients from endoscopic retrograde cholangiopancreatography examinations and image quality considerations.

The purpose of this investigation was to measure the dose-area product (DAP) and the other relevant dosimetric quantities in diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Furthermore, the dependence of patient dose and image quality on the tube potential was investigated. A DAP meter was used for dose monitoring in seven diagnostic and 21 therapeutic ERCPs. For each ERCP the DAP meter readings, fluoroscopy time, number of radiographs and exposure data were recorded. From these data the fluoroscopy and radiography contributions to DAP, the entrance skin dose and the effective dose for each examination were estimated. For the investigation of the effect of tube potential on patient dose and image quality, a water phantom containing syringes filled with diluted contrast media was used. The average DAP was 13.7 Gy cm2 in diagnostic and 41.8 Gy cm2 in therapeutic ERCP whereas the average fluoroscopy times were 3.1 and 6.0 min respectively. DAP was strongly correlated to the fluoroscopy time. Measurements in the phantom showed that a good compromise between image quality and patient dose is obtained for tube potentials around 80 kV. Therapeutic ERCPs deliver on average higher doses to patients than diagnostic ERCPs. However, for a difficult diagnostic ERCP more patient exposure may be required than for a simple therapeutic ERCP.

Impaired nitric oxide function in the basilar artery of the obese Zucker rat.

The effect of insulin-resistance syndrome on vascular function has been examined in isolated basilar arteries using the obese Zucker rat (OZR) and age-matched lean littermate controls (lean Zucker rat; LZR) at 36 weeks of age. The OZR showed significantly reduced oral glucose tolerance and increased body weight, blood pressure, proteinuria, plasma levels of triglycerides, cholesterol, and insulin compared with the LZR. The contractile response to serotonin was significantly increased in the OZR. Furthermore, contractions to serotonin in LZR but not OZR were enhanced in the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (NAME). Relaxations to acetylcholine (ACh), histamine, and A23187 were significantly reduced in precontracted arteries from the OZR. In the presence of NAME, histamine responses were significantly reduced whereas ACh and A23187 responses were almost abolished. Relaxations to free-radical nitric oxide (NO) and papaverine were not different in arteries from the OZR, even though responses to sodium nitroprusside were reduced in the OZR. Western blot and immunofluorescent quantitative analyses of eNOS content in cerebral microvessel fractions and basilar artery preparations, respectively, were not significantly different between OZR and LZR. The results suggest impairment in endothelial function resulting in reduced NO function in the basilar artery from the OZR.

Intracellular pH homeostasis during cell-cycle progression and growth state transition in Schizosaccharomyces pombe.

Accurate measurement of intracellular pH in unperturbed cells is fraught with difficulty. Nevertheless, using a variety of methods, intracellular pH oscillations have been reported to play a regulatory role in the control of the cell cycle in several eukaryotic systems. Here, we examine pH homeostasis in Schizosaccharomyces pombe using a non-perturbing ratiometric pH sensitive GFP reporter. This method allows for accurate intracellular pH measurements in living, entirely undisturbed, logarithmically growing cells. In addition, the use of a flow cell allows internal pH to be monitored in real time during nutritional, or growth state transition. We can find no evidence for cell-cycle-related changes in intracellular pH. By contrast, all data are consistent with a very tight homeostatic regulation of intracellular pH near 7.3 at all points in the cell cycle. Interestingly, pH set point changes are associated with growth state. Spores, as well as vegetative cells starved of either nitrogen, or a carbon source, show a marked reduction in their internal pH compared with logarithmically growing vegetative cells. However, in both cases, homeostatic regulation is maintained.

The pub1 E3 ubiquitin ligase negatively regulates leucine uptake in response to NH(4)(+) in fission yeast.

Fission yeast strains auxotrophic for leucine are unable to proliferate in normally supplemented minimal media adjusted to pH 6. 4 or above. High-pH sensitivity can be suppressed by the loss of Pub1, an E3 ubiquitin ligase, or by the replacement of NH(4)(+) with a non-repressing source of nitrogen such as L-proline. In this report we show pub1 to be required for the rapid down-regulation of leucine uptake observed in response to the addition of NH(4)(+) to the growth media. Furthermore, we corroborate earlier results demonstrating the transport of leucine to be negatively influenced by high extracellular pH. pub1 is homologous to the budding yeast nitrogen permease inactivator, NPI1/RSP5, which mediates the ubiquitination and subsequent destruction of NH(4)(+)-sensitive permeases. The high-pH sensitivity of cells auxotrophic for leucine thus seems to reflect an inability of NH(4)(+)-insensitive permeases to transport sufficient leucine under conditions where the proton gradient driving nutrient transport is low, and NH(4)(+)-sensitive permeases have been destroyed. Intriguingly, the partial suppression of both high pH sensitivity, and the inactivating effect of NH(4)(+) on leucine transport, seen in pub1-1 point mutants, becomes as complete as seen in pub1Delta backgrounds when cells have concomitantly lost the function of the spc1 stress-activated MAPK.

Comparison of the redox forms of nitrogen monoxide with the nitrergic transmitter in the rat anococcygeus muscle.

1. A sustained tone was produced in rat isolated anococcygeus muscles with guanethidine and clonidine and relaxant responses were elicited by electrical stimulation of its nitrergic nerves and by the three redox forms of nitrogen monoxide. 2. The nitroxyl anion (NO ) was donated by dissociation of Angeli's salt; the free radical (NO*) was from an aqueous solution of nitric oxide gas; the nitrosonium cation (NO+) was donated by dissociation of nitrosonium tetrafluoroborate. 3. The concentrations producing approximately 50% relaxations of the anococcygeus muscle were 0.3 microM for Angeli's salt (nitroxyl), 0.5 microM for NO* and 100 microM for nitrosonium tetrafluoroborate. Nitrergic nerve stimulation at 1 Hz for 10 s produced equivalent relaxant responses. 4. The superoxide generator pyrogallol (100 microM) had no effect on responses to nitrergic nerve stimulation or Angeli's salt but significantly reduced responses to NO* and nitrosonium tetrafluoroborate. 5. The NO* scavenger carboxy-PTIO (100 microM) had no effect on responses to nitrergic nerve stimulation or Angeli's salt but significantly reduced responses to NO* and nitrosonium tetrafluoroborate. 6. Hydroxocobalamin (30 microM) had no significant effect on responses to the nitrergic transmitter, enhanced the response to Angeli's salt, and significantly reduced responses to NO* and nitrosonium tetrafluoroborate. 7. The findings suggest that the nitroxyl anion donated by Angeli's salt is a better candidate than NO* to serve as the nitrergic transmitter in the rat anococcygeus muscle, although it still does not behave exactly like the transmitter.

Tolerance of low pH in Schizosaccharomyces pombe requires a functioning pub1 ubiquitin ligase.

A strain of Schizosaccharomyces pombe carrying a disrupted Na+/H+ antiporter gene (sod2::sup3-5), in addition to the common auxotrophic mutations, ade6-216, ura4-D18 and leu1-32, is highly sensitive to media adjusted to pH 6.9. Reversion analysis of this strain yielded a group of revertants capable of growth at pH 6.9. Two of the revertants elongated and failed to form colonies at pH 3.5. Genetic characterization of one of the pH-sensitive elongated strains, J227, showed the presence of two independently segregating mutations. One, pub1 (protein ubiquitin ligase 1), has recently been reported as an E3 protein ubiquitin ligase involved in cdc25 turnover. The second has been named elp3-1 (elongated at low pH). Genetic dissection of the original strain revealed that poor growth at high pH was due to the presence of the auxotrophic markers, suggesting a possible inhibitory effect of high pH on the function of permeases responsible for uptake of the necessary nutrients. Suppression of the high pH sensitivity required the presence of both the pub1-1 and elp3-1 mutations. While the pub1-1 mutation reduced the capacity of cells to tolerate relatively moderate concentrations of LiCl (3 mM) in liquid culture, it was capable of partially suppressing the extreme Li+ sensitivity caused by the sod2 disruption. Under these conditions, the growth of pub1-1 sod2::ura4 double mutant cells was improved over that of either pub1-1 or sod2::ura4 cells. The elp3-1 mutation had no effect on the Li+ tolerance in either wild-type or sod2::ura4 backgrounds. pub1-1 cells are elongated and incapable of colony formation at pH 3.5. In contrast, elp3-1 cells are elongated at pH 3.5 and pH 5.5 (the normal pH of minimal medium) but can form colonies under both conditions. J227 cells are significantly longer than either single mutant at pH 3.5 and do not form colonies but are visually similar to elp3-1 cells at pH 5.5. Complementation cloning in the J227 background yielded a genomic clone of pub1, allowing us to define the intron-exon structure of the gene. Sequences with high homology to the predicted amino acid sequence of pub1 have been identified in Saccharomyces cerevisiae (RSP5/NPI1), human (hRPF1), mouse (mNedd4), and rat (rNedd4). Based on the nature of our mutant selection, the pH-sensitive phenotype of the strains selected, and the known involvement of RSP5/ NPI1 in membrane permease turnover in S. cerevisiae, we hypothesize a role for pub1, either directly or indirectly, in regulating membrane transport processes. This is further supported by the broad range of effects that the pub1-1 mutation exerts on overall performance of cells at high and low external pH, and in the presence of toxic levels of Li+.

Cellular hypersensitivity to a synthetic dodecapeptide derived from human adenovirus 12 which resembles a sequence of A-gliadin in patients with coeliac disease.

The human intestinal adenovirus serotype 12 (Ad12) may be implicated in the pathogenesis of coeliac disease by virtue of immunological cross reactivity between epitopes shared by its early region E1b protein and A-gliadin. In the present study a synthetic dodecapeptide from the corresponding viral epitope (Ad12E1b, residues 384-395) was tested for its effect on peripheral blood mononuclear cells from 22 treated and eight untreated patients with coeliac disease, 22 healthy subjects, 11 patients with ulcerative colitis, and 11 patients with Crohn's disease by an indirect leucocyte migration inhibition assay. In addition, the effect of both the viral and the gliadin synthetic peptides was studied by proliferation and migration assays simultaneously performed in an unselected subgroup of 12 treated coeliac patients and 12 healthy subjects of the study. Coeliac patients with untreated disease showed no response to the viral peptide compared with treated patients (p greater than 0.1). Treated coeliac patients showed a significantly different response from healthy control subjects and control patients with disease (p less than 0.001) which was dependent on the concentration of the viral peptide. In the subgroup of the treated coeliac patients (n = 12) there was a significant correlation between the responses in the migration and the proliferation assay using either the viral (p less than 0.02) or the gliadin (p less than 0.005) peptide at the highest concentration (33.3 micrograms/ml). Furthermore, the responses obtained using viral peptide correlated significantly with the responses obtained with gliadin peptide in both the migration (p less than 0.001) and the proliferation (p less than 0.001) assays. These results show that in coeliac patients there is pronounced cross reactivity at the level of T cell recognition between synthetic peptides derived from the Ad12 and A-gliadin. This antigenic cross reactivity may be involved in the pathogenesis of coeliac disease.

Functional and biochemical subtypes of the haplotype HLA-DR3 in patients with celiac disease or idiopathic membranous nephropathy.

HLA class II beta-chain polymorphism was investigated in the haplotype HLA-DR3 to determine if patients with HLA-DR3-associated diseases express normal or variant class II polymorphisms. Analysis was carried out by two-dimensional gel electrophoresis of immunoprecipitated HLA class II molecules, DNA hybridization with DR beta and DQ beta gene probes on Taq 1, Bam H1, or Rsa 1 digests, and mixed lymphocyte culture. Two subtypes of HLA-DR3 were identified in normal homozygous DR3 individuals on the basis of polymorphism in one of two DR beta chains detected, corresponding to differences in DR beta restriction fragment patterns. These polymorphisms exhibited significant linkage disequilibrium with the A1,B8,DR3 and B18,DR3 haplotypes, respectively. In proliferative experiments, cells with the B18,DR3-associated polymorphism strongly stimulated cells from donors with the B8,DR3-related polymorphism, suggesting that a T-cell epitope recognized by B8,DR3 cells lies on the B18,DR3-associated DR beta chain. In seven HLA-DR3 homozygous patients with celiac disease and three HLA-DR3-homozygous patients with idiopathic membranous nephropathy, only the normal patterns of HLA class II molecules were displayed, the B8,DR3 type occurring in all patients and the B18,DR3 type in one patient. These data suggest that celiac disease and idiopathic membranous nephropathy are not related to disease-specific HLA-DR beta or -DQ beta gene variants within the DR3 population that are revealed by these methods.

Cell-mediated immunity to a synthetic gliadin peptide resembling a sequence from adenovirus 12.

Cell-mediated immunity to a synthetic peptide, which has a 12-residue sequence from A-gliadin analogous to part of an early-region protein (Elb) from adenovirus 12, was investigated in patients with coeliac disease, healthy subjects, and disease controls by means of an indirect leucocyte-migration-inhibition assay. Patients with coeliac disease being treated with a gluten-free diet showed a significantly greater response than healthy subjects (p less than 0.001) or patients with inflammatory bowel disease. This cellular immune response was dependent on antigen concentration and was not present in untreated coeliac patients.