bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of substrate temperature on glancing angle deposited Ag nanorods
Authors: Khare C. , Patzig C. , Gerlach J. W. , Rauschenbach B. , Fuhrmann B.
Published: June 2010

When Ag sculptured thin films were grown with glancing angle deposition by ion beam sputtering at either room temperature or elevated substrate temperatures TS, a large morphological difference was observed. The incident particle flux reached the silicon substrate at a glancing angle β≥80° as measured to the substrate normal. A slit aperture was used in order to reduce the particle beam divergence. At room temperature, columnar structures were formed, irrespective of the presence of the slit aperture. At elevated temperatures (573 and 623 K) and collimated particle flux in the presence of the slit aperture, however, enhanced surface diffusion causes the growth of crystalline nanorod- and nanowirelike structures. In the absence of the slit aperture, the flux beam divergence is higher, resulting in island- and mountainlike crystalline structures. The density of the nanorods and nanowires was observed to be higher on the planar Si substrates in comparison to honeycomblike prepatterned substrates with different pattern periods. On the patterned substrates, the nanorods are not necessarily found to be evolving on the seed points but can rather be also observed in-between the artificial seeds. The glancing angle deposited films at high temperatures were observed to be polycrystalline, where the (111) crystal orientation of the film is dominant, while the presence of the less intense (200) reflection was noticed from the x-ray diffraction measurements. In contrast, compact thin films deposited with β≈0° at high temperatures were found to be epitaxial with (200) orientation.
Genomic Architecture Characterizes Tumor Progression Paths and Fate in Breast Cancer Patients
Authors: Russnes Hege G. , Vollan Hans Kristian Moen , Lingjærde Ole Christian , Krasnitz Alexander , Lundin Pär , Naume Bjørn , Sørlie Therese , Borgen Elin , Rye Inga H. , Langerød Anita , Chin Suet-Feung , Teschendorff Andrew E. , Stephens Philip J. , Månér Susanne , Schlichting Ellen , Baumbusch Lars O. , Kåresen Rolf , Stratton Michael P. , Wigler Michael , Caldas Carlos , Zetterberg Anders , Hicks James , Børresen-Dale Anne-Lise
Published: June 2010

This study demonstrates the relation among structural genomic alterations, molecular subtype, and clinical behavior and shows that an objective score of genomic complexity can provide independent prognostic information in breast cancer.
Increasing butyrate concentration in the distal colon by accelerating intestinal transit
Authors: Lewis S J , Heaton K W
Published: June 2010

Background—Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon’s main energy source and inhibits malignant transformation in vitro.

Aim—To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools.

Patients—Thirteen healthy adults recruited by advertisement.

Methods—Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool β-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed.

Results—WGTT decreased, stool output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r=−0.511, p=0.001), with faecal butyrate (r=−0.577, p<0.001) and with distal colonic pH (r=0.359, p=0.029).

Conclusion—Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH.
Pathology of idiopathic megarectum and megacolon
Authors: Gattuso J M , Kamm M A , Talbot I C
Published: June 2010

Background—The aetiology and pathology of both idiopathic megarectum and idiopathic megacolon are unknown. In particular, it is unknown whether there are abnormalities involving enteric nerves or smooth muscle.

Methods—Resected tissue was examined from 24 patients who underwent surgery for idiopathic megarectum, from six patients who had tissue resected for idiopathic megacolon, and 17 control patients who had surgery for non-obstructing large bowel cancer. Qualitative and quantitative histological examination was performed after staining with haematoxylin and eosin, periodic acid Schiff (PAS), Martius scarlet blue (MSB), and phosphotungstic acid haematoxylin (PTAH). Neural and glial tissue were examined after immunostaining with S100 and PGP9.5.

Results—Compared with controls, patients with idiopathic megarectum had significant thickening of their muscularis mucosae (median 78 v 33 μm, p<0.005), circular muscle (1000 v 633 μm, p<0.005), and longitudinal muscle (1083v 303 μm, p<0.005), despite rectal dilatation. This thickening was relatively greater in the longitudinal than in the circular muscle. Fibrosis of the longitudinal muscle was seen, using MSB staining, in 58%, of circular muscle in 38%, and of muscularis mucosae in 29% of patients. The relation between muscle thickening and fibrosis was variable. The density of neural tissue in the longitudinal muscle seemed to be reduced in patients with idiopathic megarectum. There was no thickening of enteric muscle or alteration in the density of innervation in patients with idiopathic megacolon.

Conclusion—There is notable thickening of the enteric smooth muscle in patients with idiopathic megarectum, but the architecture of the enteric innervation seems to be intact. Functional abnormalities of the latter remain a possible cause of the smooth muscle hypertrophy.
Improving the detection rate of early gastric cancer requires more than open access gastroscopy: a five year study
Authors: Suvakovic Z , Bramble M G , Jones R , Wilson C , Idle N , Ryott J
Published: June 2010

Background/aims—To explore the reasons why patients with gastric cancer continue to present with advanced disease despite open access gastroscopy.

Patients—All patients diagnosed with gastric cancer between 1 August 1989 and 31 July 1994.

Methods—A retrospective study of the presentation of gastric cancer in South Tees; patients were diagnosed at open access gastroscopy or referred through conventional channels. Primary care records of 81 patients dying between 1991 and 1995 were analysed for previous symptoms, investigations, and antisecretory drug therapy. Findings were compared with 200 age and sex matched controls.

Results—The overall incidence of earlier stage gastric cancer remains low at 13%. Diagnostic delay occurs in both primary and secondary care due to a high incidence of previous dyspepsia and investigation. One in six patients had been previously investigated in the three years prior to diagnosis, the majority of whom were on antisecretory drugs.

Conclusions—Early gastric cancer remains rare in South Tees health district. Advantages of open access gastroscopy appear to be compromised by delayed referral to hospital and failure of endoscopists to recognise the early disease; either they are unaware of its appearance or prior treatment with an H2receptor antagonist masks the disease by allowing mucosal healing.
Spiral computed tomography and operative staging of gastric carcinoma: a comparison with histopathological staging
Authors: Davies J , Chalmers A G , Sue-Ling H M , May J , Miller G V , Martin I G , Johnston D
Published: June 2010

Background—Much controversy exists as to the value of computed tomography (CT) in the preoperative staging of gastric cancer, because of its limited ability to identify correctly lymph node (LN) metastases, invasion of adjacent organs, or hepatic and peritoneal metastases. Spiral CT scanners have a number of potential advantages over conventional scanners, including the absence of respiratory misregistration, image reconstruction smaller than scan collimation permitting overlapping slices and optimisation of intravenous contrast enhancement.

Aim—To compare the performance of spiral CT and operative assessment against formal (TNM) pathological staging.

Patients and methods—A study of 105 consecutive patients who underwent both spiral CT and operative staging was performed. All CT scans were reviewed by a radiologist who commented on tumour location and size, evidence of adjacent organ invasion, lymph node metastases to both N1 and N2 nodes, and evidence of hepatic and peritoneal metastases. All patients underwent careful operative assessment at the time of surgery, along the lines suggested by Rohde and colleagues.

Results—Spiral CT remained poor at identifying LN metastases to both N1 and N2 lymph nodes, with sensitivity ranging from 24 to 43%; specificity, however, was 100%. Operative staging was superior, with sensitivities between 84 and 94%, but specificity was much lower (63–74%). Spiral CT correctly detected 13 of 17 cases of invasion of either the colon or the mesocolon (sensitivity 76%) compared with 16 of 17 cases at operative staging (sensitivity 94%). Spiral CT correctly identified three of six cases with invasion of the pancreas (sensitivity 50%) compared with six of six cases on operative staging (sensitivity 100%). Spiral CT correctly identified 12 of 17 cases of peritoneal metastases (sensitivity 71%) and four of seven cases of hepatic metastases (sensitivity 57%).

Conclusion—Whilst spiral CT remains poor at identifying lymph node metastases, it correctly identified most cases with invasion of either the colon or the mesocolon and half the cases of pancreatic invasion. It was of value in detecting peritoneal metastases and some cases with hepatic metastases. At present, at Leeds General Infirmary spiral CT is performed routinely on all patients with gastric cancer and a selective staging laparoscopy policy is adopted in those patients in whom the status of the peritoneal cavity and liver is in doubt.
Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohn’s disease
Authors: Rachmilewitz D , Okon E , Karmeli F
Published: June 2010

Background—Sulphydryl compounds are essential for maintaining mucosal integrity in the gastrointestinal tract.

Aim—To characterise a model of experimental inflammation in the small intestine induced by a sulphydryl blocker.

Methods—Inflammation in the small intestine was induced in rats by intrajejunal administration of 0.1 ml 2% iodoacetamide. The possible amelioration of the damage induced was modulated by intragastric administration of TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 50 mg/100 g body weight), ketotifen (200 μg/100 g body weight) or by addition ofl-NAME (NG-nitro-l-arginine methyl ester; 0.1 mg/ml) or apocynin (120 μg/ml) to the drinking water. Rats were sacrificed at various time intervals, the small intestine resected, weighed, macroscopic lesions were assessed, and mucosal generation of inflammatory mediators and nitric oxide synthase activity were determined.

Results—Intrajejunal administration of iodoacetamide induced, after one week, multifocal mucosal erosions, ulcerations with granulomas and giant Langhans cells. At two weeks, the mucosa was almost macroscopically intact but histologically epithelial granuloma and giant cells were present. Myeloperoxidase activity was increased in the first 24 hours, one week later mucosal nitric oxide synthase activity and generation of leukotriene B4, leukotriene C4 and thromboxane B2 were increased, whereas prostaglandin E2 generation was decreased notably. Ketotifen and apocynin significantly decreased the extent of injury which was not affected by TEMPOL orl-NAME.

Conclusions—Jejunal inflammation induced by the sulphydryl blocker, iodoacetamide, resembles the pathological changes in Crohn’s disease. The protective effect of ketotifen and apocynin indicates the contribution of O2− and pro-inflammatory mediators to the pathogenesis of the damage, and may be a novel approach to the treatment of inflammatory bowel disease.
Intravenous immunoglobulin therapy for severe Clostridium difficile colitis
Authors: Salcedo J , Keates S , Pothoulakis C , Warny M , Castagliuolo I , LaMont J T , Kelly C P
Published: June 2010

Background—Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis.

Aims—To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy.

Patients—Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200–300 mg/kg).

Methods—Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay.

Results—Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4–1.6 mg/ml.

Conclusion—Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations andC difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration.
Detection of small hepatocellular carcinomas in cirrhotic livers using iodised oil computed tomography
Authors: Saada J , Bhattacharya S , Dhillon A P , Dick R , Burroughs A K , Rolles K , Davidson B R
Published: June 2010

Background—The detection of hepatocellular cancers (HCC) is a major role of preoperative imaging in patients with end stage liver disease being considered for orthotopic liver transplantation (OLT).

Aims—To assess the sensitivity of iodised oil computed tomography (IOCT).

Patients and methods—A prospective evaluation in 50 consecutive patients undergoing OLT included ultrasound scan, contrast enhanced CT, angiography (with intra-arterial injection of iodised oil), and a second CT (IOCT) 10 days later. Following transplantation the explant liver was serially sectioned for pathological evaluation. Soft tissue radiographs of the liver slices were used to match histological lesions with CT findings.

Results—Eleven patients were excluded due to protocol violations. Of the remaining 39, histological evaluation revealed no cancers in 33 explant livers, in keeping with negative preoperative imaging. Six explant livers contained 55 HCCs, 84% of which were less than 1 cm in diameter. Pretransplant IOCT detected 3/6 patients with cancer (50%) but only 7% of cancerous lesions. Ultrasound, contrast CT, and angiography each detected 2/6 patients with cancer and 4% of cancerous lesions.

Conclusion—IOCT is an insensitive method for the detection of small HCCs in livers with advanced cirrhosis but in this study was slightly superior to ultrasound, CT, and angiography.
High prevalence of cytotoxin positive Helicobacter pylori in patients unrelated to the presence of peptic ulcers in Japan
Authors: Ogura K , Kanai F , Maeda S , Yoshida H , Ogura M , Lan K-H , Hirota K , Kawabe T , Shiratori Y , Omata M
Published: June 2010

Background—It has been reported that infection with vacuolating cytotoxin positive Helicobacter pyloristrains is associated with gastroduodenal disease in Western countries.

Aims—To evaluate the prevalence of cytotoxin producing strains among patients with H pyloriinfection in relation to gastrointestinal diseases in Japan.

Patients—Ninety seven patients undergoing endoscopy.

Methods—A Western blot assay was conducted to detect serum antibodies against the cytotoxin using recombinant cytotoxin (VacA protein) as an antigen. To obtain a purified recombinant cytotoxin, the vacA gene (2233 nucleotides) was cloned into an expression vector to produce the protein (744 amino acids), which was expressed in Escherichia coli.

Results—Serum IgG antibodies to the cytotoxin were present in 85%, 95%, 95%, and 100% of infected patients with gastric ulcer (n=26), duodenal ulcer (n=21), chronic gastritis (n=19), and endoscopically normal mucosa (n=14), respectively.

Conclusion—The western blot method using recombinant VacA protein is simple and useful for detecting antibody to vacuolating cytotoxin. This method showed antibodies against cytotoxin were highly prevalent, even in subjects with endoscopically normal mucosa in Japan, indicating that the cytotoxin may not be an independent cause of gastrointestinal diseases induced by H pylori infection.
Primary ileal villous atrophy is often associated with microscopic colitis
Authors: Marteau P , Lavergne-Slove A , Lemann M , Bouhnik Y , Bertheau P , Becheur H , Galian A , Rambaud J C
Published: June 2010

Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis.
Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?
Authors: Briet F , Pochart P , Marteau P , Flourie B , Arrigoni E , Rambaud J C
Published: June 2010

Background—Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption. Adaptation of the colonic flora might explain this improvement.

Aims—To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose.

Methods—Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15. Between these days they were given 34 g of lactose or sucrose per day, in a double blind protocol. Stool samples were obtained on days 0 and 14, to measure faecal β-galactosidase and pH. Symptoms, breath H2 excretion, faecal weight and electrolytes, and orofaecal transit time were assessed.

Results—Except for faecal weight, symptoms were significantly milder during the second challenge in both groups, and covariance analysis showed no statistical difference between them. In the lactose group, but not in the sucrose group, faecal β-galactosidase activity increased, pH dropped, and breath H2 excretion decreased.

Conclusion—Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days, and all symptoms except diarrhoea regressed. Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation. This suggests that improved clinical tolerance may be just a placebo effect.
The distal colon provides reserve storage capacity during colonic fluid overload
Authors: Hammer J , Pruckmayer M , Bergmann H , Kletter K , Gangl A
Published: June 2010

Background—In addition to its absorptive function the capacity of the colon to retain fluid might be relevant in compensating for increased fluid loads and prevention of diarrhoea. The distal colon is considered to be mainly a conduit without extensive storage function.

Aims—To evaluate colonic volume capacity in a model of pure osmotic diarrhoea.

Methods—A non-absorbable, iso-osmotic solution (OS) containing polyethylene glycol (500 ml) was infused into the caecum of nine healthy volunteers; the control group (n=5) received an equal amount of an easily absorbable electrolyte solution (ES). Fluids were radiolabelled with technetium-99m and gamma camera images were obtained for 48 hours. Counts in the proximal and distal colon were measured and regional and overall colonic transit and stool output were quantified.

Results—After OS, in contrast to ES, faecal output was increased significantly (p<0.05), but colonic transit after OS was not different from transit after ES (p>0.05). This indicates storage of OS in the colon: after OS infusion, counts in the proximal colon decreased linearly while the distal colon stored approximately 30% of radioactivity for the whole 48 hour study period. After OS, stool output correlated with distal (p<0.01), but not with proximal (p>0.05), colonic transit. In constrast, after ES, stool output was determined by proximal colonic transit (p<0.05) but not by transit through the distal colon (p>0.05).

Conclusion—The distal colon retains non-absorbable fluid volumes extensively. In our model transit through the distal colon—but not the proximal colon—determined the time at which diarrhoea occurred.
Do patients with irritable bowel syndrome in primary care really differ from outpatients with irritable bowel syndrome?
Authors: van der Horst H E , van Dulmen A M , Schellevis F G , van Eijk J Th M , Fennis J F M , Bleijenberg G
Published: June 2010

Background—Little is known about the comparability of outpatients with irritable bowel syndrome (IBS) and patients with IBS in primary care with regard to severity of complaints, perceived limitations, other aspects of the complaints, and sex differences.

Aims—To compare outpatients with IBS with primary care patients with IBS.

Patients—One hundred and nine patients with IBS were recruited from general practices in Amsterdam and 86 patients with IBS were recruited from the outpatient clinic of the Department of Internal Medicine of the University Hospital in Nijmegen.

Methods—Each patient completed a questionnaire on demographic variables, abdominal complaints, related complaints, and attributed causes of their abdominal complaints. The scores of the two groups were compared by univariate and multivariate analysis.

Results—The outpatient group contained significantly more men, reported more severe abdominal pain, more frequent complaints, more interference with daily activities, and a higher degree of avoidance of activities (p<0.01) than the primary care group. When each sex was analysed separately, these differences remained for female (p<0.01) but not for male patients. Outpatients were more likely to attribute their complaints to somatic causes (p<0.01), whereas primary care patients were more likely to attribute their complaints to stress (p<0.01) or their agitated way of life (p<0.05). Multivariate analysis showed that a high severity score, a large number of additional complaints, and a low score on the stress attribution were important determinants for being in the outpatient group.

Conclusions—Female outpatients consider their complaints to be more serious and interfering than do patients with IBS in primary care. Male outpatients were comparable to primary care patients with IBS. More research needs to be done into sex specific differences in IBS and into the factors that influence the decision to refer a patient with IBS.
Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease
Authors: Crowe S E , Luthra G K , Perdue M H
Published: June 2010

Background—Mast cells have been shown to regulate intestinal ion transport in animal models and normal human colon but their physiological role in human intestinal inflammatory disorders is unknown.

Aims—To examine mast cell regulation of ion transport in inflammatory bowel disease (IBD).

Subjects and methods—Small and large intestine was obtained from patients with and without IBD undergoing surgical resection. Short circuit current (Isc) responses to rabbit antihuman IgE, histamine, and electrical stimulation were measured in Ussing chambers. Specimens were also examined for mast cell numbers and degree of inflammation.

Results—Isc responses to anti-IgE and histamine were smaller in magnitude in IBD compared with non-IBD tissues. In all tissues, anti-IgE Isc responses were reduced by about 80% in chloride free buffer. The histamine H1 receptor antagonist, pyrilamine, decreased anti-IgE responses in non-IBD tissues. Greater inhibition with pyrilamine was seen in IBD small intestine but its effect was less in IBD colon. Histamine pretreatment of non-IBD control tissues reduced anti-IgE responses to levels seen in IBD colon but had no effect in small intestine. Mast cell numbers were greater in IBD compared with non-IBD small intestine while no differences were observed between the colonic groups. Isc responses to anti-IgE were not correlated with the degree of mucosal inflammation.

Conclusions—This study provides further evidence that mast cells are capable of mediating alterations of ion transport in human gut but that this regulatory role may be altered in IBD. The data suggest that prior activation of mast cells with release of histamine may account for the reduced secretory response to anti-IgE observed in IBD colonic tissues.
Prevalence of infection with Cryptosporidium parvumand Cyclospora cayetanensis among international travellers
Authors: Jelinek T , Lotze M , Eichenlaub S , Löscher T , Nothdurft H D
Published: June 2010

Background—Cryptosporidium parvumand Cyclospora cayetanensis are recognised as possible pathogens of traveller’s diarrhoea.

Aims—To identify the prevalence of C parvumand Cyc cayetanensis in travellers returning from developing countries.

Patients—Nine hundred and seventy eight stool samples were taken from 795 patients returning from developing countries.

Methods—Microscopy (iron-haematoxylin stain, SAF concentration, modified acid fast stain) and a commercially available enzyme linked immunosorbent assay (ELISA) kit for the detection of Cryptosporidium antigen in stool.

Results—Of the 795 patients in the study, 469 suffered from diarrhoea. Infection with Cyc cayetanensiscould be detected in five subjects (1.1%) by acid fast stain, and 13 patients (2.8%) were infected with C parvum. On evaluation, the antigen capture ELISA turned out to be clearly less sensitive for detection of C parvum than microscopy. All patients with either C parvum or Cyc cayetanensis infection suffered from watery diarrhoea.

Conclusions—C parvum and Cyc cayetanensis are not major causes of diarrhoea in international travellers. In cases of persistent watery diarrhoea, however, these pathogens should be taken into account in the differential diagnosis.
Increased activity of group II phospholipase A2 in plasma in rat sodium deoxycholate induced acute pancreatitis
Authors: Furue S , Hori Y , Kuwabara K , Ikeuchi J , Onoyama H , Yamamoto M , Tanaka K
Published: June 2010

Background—Two different types of secretory phospholipase A2 (PLA2), pancreatic group I (PLA2-I) and non-pancreatic group II (PLA2-II), have been identified and postulated to be associated with the pathogenesis of various diseases, such as acute pancreatitis, septic shock, and multiple organ failure.

Aims—To investigate the type of secretory PLA2 responsible for its catalytic activity found in plasma and ascites of experimental acute pancreatitis.

Methods—Acute pancreatitis of differing severity was induced by the injection of different concentrations (1% or 10%) of sodium deoxycholate (DCA) into the common biliopancreatic duct in rats, and catalytic PLA2 activity in plasma and ascites were differentiated by anti-PLA2-I antibody and specific inhibitor of PLA2-II. Survival rate and plasma amylase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also measured.

Results—In 1% and 10% DCA induced acute pancreatitis, plasma amylase values as well as PLA2activity in ascites were greatly increased. PLA2 activity in plasma was also notably increased in 10% DCA induced acute pancreatitis, but not in 1% DCA induced acute pancreatitis. PLA2-I specific polyclonal antibody significantly inhibited PLA2 activity in ascites but not that in plasma. In contrast, plasma PLA2 activity was completely suppressed by PLA2-II specific inhibitor. In addition, a high mortality (93% at five hours) and a significant increase in plasma AST and ALT were noted in 10% DCA induced pancreatitis.

Conclusion—Ascites PLA2 activity is mainly derived from PLA2-I, whereas plasma PLA2activity is mostly derived from PLA2-II in severe acute pancreatitis, suggesting that increased plasma PLA2-II activity might be implicated in hepatic failure arising after severe acute pancreatitis.
Treatment of enteritis in chronic granulomatous disease with granulocyte colony stimulating factor
Authors: Myrup B , Valerius N H , Mortensen P B
Published: June 2010

Background—In several diseases there is a relation between deficiency of neutrophil granulocytes and granulomatous lesions. Recently, in glycogen storage disease type Ib, this relation has been supported by the beneficial effect of treatment of enteritis with granulocyte-macrophage colony stimulating factor.

Aim—To investigate whether chronic granulomatous disease could be treated according to the same principle.

Patients and methods—Inflammatory lesions were monitored in two brothers with chronic granulomatous disease demonstrated by very low superoxide production in neutrophil granulocytes. The two patients were treated with recombinant human granulocyte colony stimulating factor on three occasions when the disease was active.

Results—In one patient, remission of an inflamed stenosis of the colon sigmoideum was shown by granulocyte scintigraphy after one month of treatment with granulocyte colony stimulating factor. In the other patient, remission of colon disease and later of a non-malignant tumour in the right lung hilum was shown by colonoscopy and computed tomography scans respectively.

Conclusion—Remission of inflammatory lesions in two brothers with chronic granulomatous disease was induced by granulocyte colony stimulating factor on three occasions. The mechanism for this effect is not known. The result is similar to the response found in patients with leucocyte deficiency due to glycogen storage disease type Ib.
Microbiology of bacterial translocation in humans
Authors: O’Boyle C J , MacFie J , Mitchell C J , Johnstone D , Sagar P M , Sedman P C
Published: June 2010

Background—Gut translocation of bacteria has been shown in both animal and human studies. Evidence from animal studies that links bacterial translocation to the development of postoperative sepsis and multiple organ failure has yet to be confirmed in humans.

Aims—To examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of bacteria and the development of postoperative septic complications.

Methods—Mesenteric lymph nodes (MLN), serosal scrapings, and peripheral blood from 448 surgical patients undergoing laparotomy were analysed using standard microbiological techniques.

Results—Bacterial translocation was identified in 69 patients (15.4%). The most common organism identified wasEscherichia coli (54%). Both enteric bacteria, typical of indigenous intestinal flora, and non-enteric bacteria were isolated. Postoperative septic complications developed in 104 patients (23%). Enteric organisms were responsible in 74% of patients. Forty one per cent of patients who had evidence of bacterial translocation developed sepsis compared with 14% in whom no organisms were cultured (p<0.001). Septic morbidity was more frequent when a greater diversity of bacteria resided within the MLN, but this was not statistically significant.

Conclusion—Bacterial translocation is associated with a significant increase in the development of postoperative sepsis in surgical patients. The organisms responsible for septic morbidity are similar in spectrum to those observed in the mesenteric lymph nodes. These data strongly support the gut origin hypothesis of sepsis in humans.
Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication
Authors: van der Hulst R W M , van der Ende A , Homan A , Roorda P , Dankert J , Tytgat G N J
Published: June 2010

Background—Metronidazole-containing eradication therapies are less effective for metronidazole resistantHelicobacter pylori. Although early data suggested improvement of the efficacy of bismuth triple therapy after the addition of acid suppressives, these findings were based on studies with small numbers of patients, incomplete post-eradication follow up, or omission of pretreatment susceptibility testing.

Aims—To study the efficacy of quadruple therapy in the Amsterdam area, where the efficacy of bismuth triple therapy has been proved to be affected by metronidazole resistance.

Patients and methods—Eighty two consecutive dyspeptic H pylori positive patients with either metronidazole susceptible (group I) or metronidazole resistant H pylori strains (group II) received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day; metronidazole 500 mg three times a day. Susceptibility to metronidazole was determined by the E-test.

Results—Intention to treat analysis showed thatH pylori infection had been cured in 42/43 patients (98%) in group I and 32/39 patients (82%) in group II (p = 0.02).

Conclusion—The efficacy of quadruple therapy is significantly impaired in patients infected with metronidazole resistant H pylori. Therefore a non-metronidazole-containing regimen should preferably be used in areas known to have a high prevalence of pretreatment metronidazole resistance.
Rapid modulation of electrolyte transport in Caco-2 cell monolayers by enteropathogenic Escherichia coli (EPEC) infection
Authors: Collington G K , Booth I W , Knutton S
Published: June 2010

Background and aims—The pathophysiology of enteropathogenic Escherichia coli (EPEC) diarrhoea remains uncertain. EPEC adhere to enterocytes and transduce signals which produce a characteristic “attaching and effacing” (A/E) lesion in the brush border membrane. The present in vitro study was designed to determine whether signal transduction by EPEC also influences electrolyte transport.

Methods—Caco-2 cell monolayers were rapidly infected with wild type EPEC strain E2348/69, or the signal transduction-defective mutant 14.2.1(1), and mounted in Ussing chambers.

Results—Strain E2348/69 stimulated a rapid but transient increase in short circuit current (Isc) which coincided with A/E lesion formation; this Isc response was absent on infection with strain 14.2.1(1). While the initial rise inIsc induced by E2348/69 was partially (∼35%) dependent on chloride, the remainder possibly represents an influx of sodium and amino acid(s) across the apical membrane.

Conclusions—The study directly shows that, after initial adhesion, EPEC induce major alterations in host cell electrolyte transport. The observed Isc responses indicate a rapid modulation of electrolyte transport in Caco-2 cells by EPEC, including stimulation of chloride secretion, for which signal transduction to host cells is a prerequisite.
Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines
Authors: Warhurst A C , Hopkins S J , Warhurst G
Published: June 2010

Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes.

Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differential modulation by interferon γ (IFN-γ), a product of activated T lymphocytes and natural killer cells.

Methods and results—HT29-19A, a model of the Cl− secretory crypt cell, exhibited a parallel secretion of the α chemokines IL-8 and GROα, which could be markedly upregulated by tumour necrosis factor α (TNF-α) and IL-1β. These cells showed no significant expression of the β chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1α (macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-γ in combination with TNF-α caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-γ had no significant effect on TNF-α stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of α chemokines but secreted high levels of MCP-1 in response to IL-1β. IFN-γ did not influence α or β chemokine secretion in these cells.

Conclusions—These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-γ to activate the expression of β chemokines preferentially could facilitate the development of chronic inflammatory infiltrates.
Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease
Authors: McAlindon M E , Hawkey C J , Mahida Y R
Published: June 2010

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD).

Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa.

Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay).

Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p<0.01).

Conclusions—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.
Motor function of the proximal stomach and visceral perception in gastro-oesophageal reflux disease
Authors: Penagini R , Hebbard G , Horowitz M , Dent J , Bermingham H , Jones K , Holloway R H
Published: June 2010

Background—The abnormally high postprandial rate of transient lower oesophageal sphincter relaxations seen in patients with reflux disease may be related to altered proximal gastric motor function. Heightened visceral sensitivity may also contribute to reporting of symptoms in these patients.

Aims—To assess motor function of the proximal stomach and visceral perception in reflux disease with a barostat.

Methods—Fasting and postprandial proximal gastric motility, sensation, and symptoms were measured in nine patients with reflux disease and nine healthy subjects. Gastric emptying of solids and liquids was assessed in six of the patients on a different day (and compared to historical controls).

Results—Minimal distending pressure and gastric compliance were similar in the two groups, whereas the patients experienced fullness at lower pressures (p<0.05) and discomfort at lower balloon volumes (p<0.005) during isobaric and isovolumetric distensions respectively. Maximal gastric relaxation induced by the meal was similar in the two groups. Late after the meal, however, proximal gastric tone was lower (p<0.01) and the score for fullness higher (p<0.01) in the reflux patients, in whom the retention of both solids and liquids in the proximal stomach was greater (p<0.05).

Conclusions—Reflux disease is associated with delayed recovery of proximal gastric tone after a meal and increased visceral sensitivity. The former may contribute to the increased prevalence of reflux during transient lower oesophageal sphincter relaxations and the delay in emptying from the proximal stomach, whereas both may contribute to symptom reporting.
The effect of flufenamic acid on gastrointestinal myoelectrical activity and transit time in dogs
Authors: Farrugia G , Nitecki S , Harty G J , Camilleri M , Szurszewski J H
Published: June 2010

Background—Flufenamic acid, a fenamate, has been shown to alter markedly the membrane potential of small intestinal smooth muscle and increase intracellular calcium in single cells.

Aims—To determine the effects of flufenamic acid on myoelectrical motor activity and gastrointestinal transit in the intact animal.

Methods—Myoelectrical motor activity was recorded via seromuscular platinum electrodes sutured at regular intervals in the stomach and throughout the small intestine. Fasted and fed gastrointestinal transit was assessed using technetium-99m (99mTc) as the radioactive marker linked to 1 mm amberlite pellets or added to the meal.

Results—Flufenamic acid (600 mg, intravenously) induced intense spike activity in the small intestine. The mean duration of irregular spike activity was 250 (7) minutes. Spike activity was more pronounced in the lower small intestine. Flufenamic acid also accelerated initial gastric emptying and markedly shortened transit time in the small intestine. In the fasted state the 50% transit time in the small intestine was 54 (8) minutes with infusion of flufenamic acid compared with 105 (10) minutes in the control group; in the fed state 99mTc first reached the colon at 220 (10) minutes compared with 270 (12) minutes in the control group.

Conclusions—Flufenamic acid had marked effects on both myoelectrical motor complex activity and small intestinal transit in the dog. The observed effects suggest that flufenamic acid may be of potential use as a prokinetic agent.
Acute effect of propranolol and isosorbide-5-mononitrate administration on renal blood flow in cirrhotic patients
Authors: Stanley A J , Bouchier I A D , Hayes P C
Published: June 2010

Background—Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies have suggested that these drugs may compromise renal function, possibly by reducing renal blood flow.

Aims—To assess the acute effects of propranolol and ISMN on renal blood flow and other haemodynamic parameters in cirrhosis.

Patients and methods—Twenty six cirrhotic patients were given either 80 mg propranolol, 20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF), azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and heart rate (HR) were recorded prior to and one hour after drug administration.

Results—Propranolol caused a reduction in HR (p<0.005), AZBF (p<0.01), and HVPG (p=0.05), but no change in MAP or RBF (454.1 (77.3) versus 413.9 (60.3) ml/min). ISMN reduced MAP (p<0.005) and HVPG (p<0.01), but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min). Combined treatment reduced MAP (p<0.005), AZBF (p<0.05), and HVPG (p=0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained unchanged.

Conclusions—Despite the anticipated changes in other haemodynamic parameters, acute propranolol and/or ISMN administration did not reduce RBF. These drugs do not seem to compromise RBF in cirrhosis.
Effect of endoscopic sphincterotomy on gall bladder bile lithogenicity and motility
Authors: Sharma B C , Agarwal D K , Baijal S S , Negi T S , Choudhuri G , Saraswat V A
Published: June 2010

Background—Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals.

Aims—To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy.

Patients—A study was performed of gall bladder bile composition and gall bladder motility in patients with gallstone disease ((n = 20; age 40–60 years, median age 55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had received endoscopic sphincterotomy for common bile duct stones. Age and sex matched disease controls comprised 20 patients with gallstone disease but without stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and diseased gall bladder without gall bladder calculi (n = 10)).

Methods—Gall bladder motility was assessed by ultrasound. Duodenal bile collected by nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid infusion was analysed for cholesterol, phospholipid, and bile acid concentrations, cholesterol saturation index, and nucleation time.

Results—There was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4 (2.5) ml; p<0.001) and mean (SEM) residual volume (4.34 (0.9) ml v14.7 (0.98) ml; p<0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6 (5.52)%; p<0.001) and mean (SEM) rate constant of gall bladder emptying (−0.031/min v−0.020/min; p<0.01) in patients who had been subjected to endoscopic sphincterotomy. Median nucleation time was significantly longer (17 days v 6 days; p<0.006) in treated patients. There was a reduction in total mean (SEM) lipid concentrations (6.73 (0.32) g/dlv 7.72 (0.84) g/dl; p<0.05), cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p<0.001) and CSI (0.72 (0.15) v 1.32 (0.31); p<0.001). There was no significant change in mean (SEM) phospholipid (25.6 (3.5) mmol/l v23.4 (6.28) mmol/l) and bile acid (93.7 (7.31) mmol/l v105.07 (16.6) mmol/l) concentrations.

Conclusions—After endoscopic sphincterotomy there was enhanced contractility of the gall bladder, accompanied by a prolongation of nucleation time and reduction in cholesterol saturation index.