bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental pain in the stomach: a model based on electrical stimulation guided by gastroscopy
Authors: Drewes A M , Arendt-Nielsen L , Jensen J H , Hansen J B , Krarup H B , Tage-Jensen U
Published: June 2010

Background—Abdominal pain is often variable in intensity and difficult to characterise due to its referred pain pattern. Clinical pain is furthermore confounded by various emotional and cognitive factors.

Aims—To develop and apply an experimental model to induce localised gastric pain.

Subjects—Twelve healthy male volunteers.

Methods—Stimulating electrodes were mounted on a biopsy forceps and electric stimuli were delivered during gastroscopy. Single, five repeated, and continuous stimuli were given at four locations in the stomach. Pain detection thresholds and pain intensities were assessed together with localisation of the referred pain area.

Results—Pain detection thresholds were higher in the prepyloric region compared with those obtained at the lesser and greater curvature. Increasing stimulus intensity resulted in augmented pain perception and repeated stimuli elicited pain at a lower stimulus intensity than single stimuli. Continuous stimuli evoked constant (33%), increasing (33%), or decreasing (33%) pain. The localisation of referred pain varied considerably in the subjects.

Conclusions—The model seems relevant to study basic pain mechanisms elicited by localised stimuli in the stomach. The experimental data support the premise that a gastric focus should always be suspected in patients referred with different kinds of abdominal pain.
Predictive factors in the outcome of pseudocysts complicating alcoholic chronic pancreatitis
Authors: Gouyon B , Lévy P , Ruszniewski P , Zins M , Hammel P , Vilgrain V , Sauvanet A , Belghiti J , Bernades P
Published: June 2010

Aims—To determine the clinical, biochemical, and/or morphological features which could predict the need for treatment of pseudocysts at diagnosis in a homogeneous population of patients with alcoholic chronic pancreatitis.

Methods—Between January 1983 and December 1993, all patients followed for alcoholic chronic pancreatitis complicated by pseudocysts and confirmed by computed tomography (CT) scan at diagnosis were studied retrospectively. Two groups of pseudocysts were considered according to their pattern of evolution and the therapeutic requirements. Group I included 45 pseudocysts that regressed spontaneously (25 patients) or that persisted without symptoms (20 patients). Group II included 45 pseudocysts with persisting symptoms or complications, requiring surgical or non-surgical treatment. The evolution of pseudocysts was monitored by CT scanning or abdominal ultrasound. Initial CT scans of all patients were reviewed by an experienced radiologist. For each patient with pseudocysts, the following morphological parameters were recorded: number of pseudocysts, maximal diameter, location, intrapancreatic or extrapancreatic development, complications related to the pseudocyst, pancreatic calcifications, enlargement of the main pancreatic duct, and signs of recent acute pancreatitis. Univariate analysis, and then multivariate analysis with all significant variables on univariate analysis were performed.

Results—On univariate analysis, location of pseudocysts in the pancreatic head and intrapancreatic development of pseudocysts were significantly more frequent in group I than in group II (78% versus 55%, p<0.02 and 89% versus 60%, p<0.001, respectively). The median diameter of pseudocysts was significantly smaller in group I than in group II (25 (10–110) mm and 40 (10–120) mm respectively, p<0.001). No differences between groups I and II were found for the clinical or biochemical parameters. Multivariate analysis showed that the intrapancreatic development of pseudocysts and a diameter less than 4 cm were the only independent factors associated with a spontaneous and favourable outcome. These factors accounted for 20% of the total variance.

Conclusions—Pseudocysts larger than 4 cm and extrapancreatic development can be considered independent predictive factors of persisting symptoms and/or complications in patients with pseudocysts and alcoholic chronic pancreatitis.
Clinical outcome of transfemoral embolisation in patients with arteriovenous malformations of the liver in hereditary haemorrhagic telangiectasia (Weber-Rendu-Osler disease)
Authors: Caselitz M , Wagner S , Chavan A , Gebel M , Bleck J S , Wu A , Schlitt H J , Galanski M , Manns M P
Published: June 2010

Background—Arteriovenous malformations of the liver in Osler’s disease may present as high output cardiac failure. A few case reports suggested that treatment with arterial embolisation may have beneficial effects in such patients.

Aims—To investigate the efficacy and safety of this treatment modality in a prospective pilot study.

Patients and methods—Four women and one man (aged 39–59 years) with the dominant hepatic manifestation of Osler’s disease presented with symptoms of cardiac failure and elevated cardiac output. Arteriovenous malformations were treated in three to five sessions with arterial embolisation using coils. The outcome was analysed by measurement of cardiac output and scoring of clinical symptoms.

Results—Embolisation was technically feasible in all patients and adequate occlusion of vascular malformations was achieved in four patients. After completion of therapy symptoms improved in four patients, while one patient suffered from abdominal pain due to cholangitis. One patient died seven months after the embolisation treatment from variceal bleeding. Mean cardiac output significantly decreased from 14.2 (range 12–17.3) l/min to 8 (range 5.9–10.6) l/min (p=0.043). After a median follow up of 23 months (range 7–50 months), three of five patients had a long lasting improvement of clinical symptoms and cardiac function.

Conclusions—This first treatment series of patients with dominant hepatic involvement in Osler’s disease indicates that arterial embolisation may prevent cardiac failure by significantly lowering cardiac output.
Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region
Authors: Bruno M J , Haverkort E B , Tijssen G P , Tytgat G N J , van Leeuwen D J
Published: June 2010

Background—Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea. This may contribute to the profound weight loss that often occurs in these patients.

Aims—To investigate whether pancreatic enzyme replacement therapy prevents this weight loss.

Patients—Twenty one patients with unresectable cancer of the pancreatic head region with suspected pancreatic duct obstruction, a biliary endoprosthesis in situ, and a Karnofsky performance status greater than 60.

Methods—Randomised double blind trial of eight weeks with either placebo or high dose enteric coated pancreatin enzyme supplementation. All patients received dietary counselling.

Results—The mean difference in the percentage change of body weight was 4.9% (p=0.02, 95% confidence interval for the difference: 0.9 to 8.9). Patients on pancreatic enzymes gained 1.2% (0.7 kg) body weight whereas patients on placebo lost 3.7% (2.2 kg). The fat absorption coefficient in patients on pancreatic enzymes improved by 12% whereas in placebo patients it dropped by 8% (p=0.13, 95% confidence interval for the difference: –6 to 45). The daily total energy intake was 8.42 MJ in patients on pancreatic enzymes and 6.66 MJ in placebo patients (p=0.04, 95% confidence interval for the difference: 0.08 to 3.44).

Conclusions—Weight loss in patients with unresectable cancer of the pancreatic head region and occlusion of the pancreatic duct can be prevented, at least for the period immediately after insertion of a biliary endoprosthesis, by high dose enteric coated pancreatin enzyme supplementation in combination with dietary counselling.
Effect of gastric acid suppressants on human gastric motility
Authors: Parkman H P , Urbain J-L C , Knight L C , Brown K L , Trate D M , Miller M A , Maurer A H , Fisher R S
Published: June 2010

Background—The effect of histamine H2receptor antagonists on gastric emptying is controversial.

Aims—To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying.

Patients and methods—Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10–15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week.

Results—Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p<0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index.

Conclusions—Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility.
Role of capsaicin sensitive nerves in epidermal growth factor effects on gastric mucosal injury and blood flow
Authors: Kang J Y , Teng C H , Chen F C , Wee A
Published: June 2010

Background—Epidermal growth factor (EGF) and capsaicin protect against experimental gastric mucosal injury. Capsaicin exerts its gastroprotective effect by stimulating afferent neurones leading to release of calcitonin gene related peptide (CGRP) which causes gastric hyperaemia. EGF also causes gastric hyperaemia but whether it acts via capsaicin sensitive neurones is unknown.

Aims—To assess the influence of: (1) capsaicin desensitisation on EGF effects on gastric mucosal injury and gastric mucosal blood flow; and (2) close arterial infusion of hCGRP8–37, a CGRP antagonist, on EGF effects on gastric mucosal blood flow.

Methods—The absolute ethanol induced gastric mucosal injury model in the rat was used. Gastric mucosal damage was assessed by planimetry and light microscopy. Gastric mucosal blood flow was measured by laser Doppler flowmetry in a gastric chamber preparation.

Results—Capsaicin desensitisation abolished the gastroprotective and gastric hyperaemic effects of EGF. Close arterial infusion of hCGRP8–37 antagonised the hyperaemic effect of both capsaicin and EGF.

Conclusion—Results show that EGF may exert its gastroprotective and gastric hyperaemic effects via capsaicin sensitive afferent neurones.
Intestinal metaplasia at the gastro-oesophageal junction:Helicobacter pylori gastritis or gastro-oesophageal reflux disease?
Authors: Hackelsberger A , Günther T , Schultze V , Manes G , Dominguez-Muñoz J-E , Roessner A , Malfertheiner P
Published: June 2010

Background—Intestinal metaplasia, whether in the cardia or the distal oesophagus, has been uniformly defined as specialised columnar epithelium, suggesting a relation with Barrett’s oesophagus. It is, however, not clear whether the risk factors associated with intestinal metaplasia are identical at both sites.

Aims—To investigate biopsy specimens obtained below the squamocolumnar junction (SCJ) in relation to endoscopic aspect, gastric histology, and clinical presentation.

Patients and methods—In 423 patients investigated the endoscopic aspect of the SCJ was classified as unremarkable (group I, n=315) or suggestive of Barrett’s oesophagus (group II, n=108). Standardised biopsy specimens from the antrum, corpus, and directly below the SCJ were investigated.

Results—Intestinal metaplasia was detected at the SCJ in 13.4% of group I patients, where it was significantly associated with gastric intestinal metaplasia (odds ratio (OR) 6.96; confidence interval (CI) 2.48 to 19.54) andH pylori (OR 7.85; CI 2.82 to 21.85), and in 34.3% of group II patients where it was significantly associated with reflux symptoms (OR 19.98; CI 6.12 to 65.19), erosive oesophagitis (OR 12.16; CI 3.86 to 38.24), and male sex (OR 6.25, CI 2.16 to 18.14), but not with H pylori or gastric intestinal metaplasia.

Conclusion—This study suggests that the pathogenesis of intestinal metaplasia at the SCJ is not uniform: at an endoscopically unremarkable SCJ it is a sequela ofH pylori gastritis, but coexisting with endoscopic features of Barrett’s oesophagus it is associated with male sex and gastro-oesophageal reflux disease.
Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo
Authors: Bardhan K D , Cherian P , Vaishnavi A , Jones R B , Thompson M , Morris P , Brooks A , D’Silva J , Gillon K R W , Wason C , Patterson J , Polak J , Bishop A
Published: June 2010

Aims—To investigate the efficacy of daily maintenance treatment with omeprazole 10 mg in reducing the relapse rate of healed erosive oesophagitis.

Methods—Three hundred patients with erosive oesophagitis (grade 2 or greater) received omeprazole 20 mg daily for 12 weeks, followed by 40 mg daily for a further 12 weeks if required. After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse the treatment cycle was repeated.

Results—The cumulative healing rate at 12 weeks in the initial healing period was 95%, and 96% and 98% on rehealing courses after relapse in the first and second maintenance periods respectively. After 12 weeks of treatment, 98% of patients were free from heartburn and 97% were free of all reflux related symptoms. Relapse in the subgroup of patients who relapsed in both maintenance periods was infrequent on omeprazole 20 mg daily: only 9% at two years. Gastrin concentrations rose above normal in one third of patients. One patient had linear hyperplasia of endocrine cells and another had micronodular hyperplasia. There were no side effects definitely attributable to omeprazole.

Conclusion—Maintenance treatment with omeprazole 10 mg daily keeps about 60% of patients with erosive oesophagitis in prolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20 mg daily.
Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings
Authors: Troncone R , Mazzarella G , Leone N , Mayer M , De Vincenzi M , Greco L , Auricchio S
Published: June 2010

Background—CD3 and γδ cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings.

Aim—To establish an in vitro system for assessing immunological changes induced by gluten in the rectum.

Patients and Methods—Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated.

Results—In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group.

Conclusions—Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.
Heterogeneity in responses by primary adult human colonic epithelial cells to purified enterotoxin of Bacteroides fragilis
Authors: Sanfilippo L , Baldwin T J , Menozzi M G , Borriello S P , Mahida Y R
Published: June 2010

Background—Enterotoxigenic strains ofBacteroides fragilis (ETBF) have been implicated in diarrhoeal illness in livestock and children, but their role in adult human colonic disease is unknown.

Aims—To investigate responses by primary adult human colonic epithelial cells to purified B fragilistoxin (BFT).

Methods—BFT was purified from culture supernatant of a highly toxigenic strain of ETBF. Morphological changes to primary colonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15 adults.

Results—BFT induced epithelial cell cytotoxicity in colonic biopsy specimens from 12/15 subjects. The BFT induced morphological changes were characterised by epithelial cell rounding, separation from adjacent cells, and detachment from the basement membrane. In severely affected specimens, almost all the epithelial cells were affected. There was heterogeneity between subjects in the rate at which BFT induced epithelial cell cytotoxicity occurred. Furthermore, in colonic biopsy specimens from three subjects, exposure to BFT did not induce any significant morphological changes to epithelial cells.

Conclusion—BFT is capable of inducing cytotoxicity in primary adult human colonic epithelial cells. Such an effect of ETBF derived BFT on epithelial cells in the colon in vivo would be expected to lead to mucosal inflammation and diarrhoea. Heterogeneity in responses by primary colonocytes probably reflects the outcome of host-BFT interactions. Such interactions in vivo could determine the occurrence of colonic disease in some individuals but not others.
Colorectal neoplasm detection using virtual colonoscopy: a feasibility study
Authors: Fenlon H M , Nunes D P , Clarke P D , Ferrucci J T
Published: June 2010

Background—Virtual colonoscopy is a potentially powerful tool for non-invasive colorectal evaluation. In vitro studies have established its accuracy in simulated polyp detection but little data exist regarding its use in clinical practice.

Aims—To evaluate the ability of virtual colonoscopy to detect colorectal cancers and polyps in patients with endoscopically proven colorectal neoplasms and to correlate the findings of virtual colonoscopy with those of conventional colonoscopy, surgery, and histopathology.

Patients—Thirty eight patients with endoscopic findings suggestive of colorectal carcinoma.

Methods—Virtual colonoscopy was performed using thin section helical computed tomography (CT) of the abdomen and pelvis after rectal insufflation of room air. Commercially available software was used to generate endoscopic “fly through” examinations of the colon from the CT data. Results were correlated with the findings of conventional colonoscopy and with the surgical and histopathological outcome in each case.

Results—Thirty eight pathologically proven colorectal cancers and 23 adenomatous polyps were present. On virtual colonoscopy, all cancers and all polyps measuring greater than 6 mm in size were identified; there were two false positive reports of polyps. On conventional colonoscopy, there was one false positive report of a malignant sigmoid stricture; four subcentimetre polyps were overlooked. Virtual colonoscopy enabled visualisation of the entire colon in 35 patients; conventional colonoscopy was incomplete in 14 patients. Virtual colonoscopy correctly localised all 38 cancers, compared with 32 using conventional colonoscopy.

Conclusion—Virtual colonoscopy is a feasible method for evaluating the colon; it may have role in diagnosis of colorectal cancer and polyps.
Transabdominal bowel sonography for the detection of intestinal complications in Crohn’s disease
Authors: Gasche C , Moser G , Turetschek K , Schober E , Moeschl P , Oberhuber G
Published: June 2010

Background

The course of Crohn’s disease is characterised by the occurrence of intestinal complications such as strictures, intra-abdominal fistulas, or abscesses. Standard diagnostic procedures may fail to show these complications, in particular fistulas.

Aims

To test the value of transabdominal bowel sonography (TABS) for the detection of intestinal complications in Crohn’s disease.

Methods

TABS was prospectively performed in 213 patients with Crohn’s disease in a university based inflammatory bowel disease referral centre. Thirty three underwent resective bowel surgery and were included in this study. The accuracy of TABS to detect strictures, intra-abdominal fistulas, or abscesses was compared with surgical and pathological findings.

Results

TABS was able to identify strictures in 22/22 patients and to exclude it in 10/11 patients (100% sensitivity, 91% specificity). Fistulas were correctly identified in 20/23 patients and excluded in 9/10 patients (87% sensitivity, 90% specificity). Intra-abdominal abscesses were correctly detected in 9/9 patients and excluded in 22/24 patients (100% sensitivity, 92% specificity).

Conclusions

In experienced hands TABS is an accurate method for the detection of intestinal complications in Crohn’s disease. TABS is thus recommended as a primary investigative method for evaluation of severe Crohn’s disease.
Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance
Authors: Sifrim D , Silny J , Holloway R H , Janssens J J
Published: June 2010

Background

Belching has been proposed as a major mechanism underlying acid gastro-oesophageal reflux in normal subjects. However, the presence of oesophageal gas has not been measured directly but only inferred from manometry.

Aims

To investigate, using intraluminal electrical impedance, the patterns of gas and liquid reflux during transient lower oesophageal sphincter (LOS) relaxations, the main mechanism of acid reflux in normal subjects.

Methods

Impedance changes associated with the passage of gas were studied in vitro, and in vivo in cats. Oesophageal manometry, pH, and intraluminal electrical impedance measurements were performed in 11 normal subjects after a meal.

Results

Gas reflux caused a sudden increase in impedance that propagated rapidly to the proximal oesophagus whereas liquid reflux induced a retrogressively propagated fall in impedance. Impedance showed gas or liquid reflux during most (102/141) transient LOS relaxations. When acid reflux occurred, impedance showed evidence of intraoesophageal retrograde flow of liquid in the majority (78%) of events. Evidence of gas retroflow was found in almost half (47%) of acid reflux episodes. When present together, however, liquid preceded gas on 44% of occasions. Overall, gas reflux occurred as the initial event in only 25% of acid reflux episodes.

Conclusions

These findings suggest that in upright normal subjects, although belching can precipitate acid reflux, most acid reflux occurs as a primary event.
Glucagon-like peptide-1: a potent regulator of food intake in humans
Authors: Gutzwiller J-P , Göke B , Drewe J , Hildebrand P , Ketterer S , Handschin D , Winterhalder R , Conen D , Beglinger C
Published: June 2010

Background/Aims

Studies in animals suggest a physiological role for glucagon-like peptide-1-(7–36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated.

Subjects—Sixteen healthy male subjects were examined in a double blind placebo controlled fashion.

Methods

The effect of graded intravenous doses (0, 0.375, 0.75, and 1.5 pmol/kg/min) of synthetic human GLP-1 on food intake and feelings of hunger and satiety was tested in healthy volunteers.

Results

Graded GLP-1 infusions resulted in a dose dependent reduction in food intake (maximal inhibition 35%, p<0.001 vcontrol) and a similar reduction in calorie intake (32%; p<0.001). Fluid ingestion was also reduced by GLP-1 (18% reduction, p<0.01). No overt side effects were produced by GLP-1, but subjects experienced less hunger and early fullness in the period before a meal during GLP-1 infusion at the highest dose (p<0.05).

Conclusions

Intravenous infusions of GLP-1 decrease spontaneous food intake even at physiological plasma concentrations, implying an important role for GLP-1 in the regulation of the early satiety response in humans.
Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?
Authors: Lim A G , Langmead F L , Feakins R M , Rampton D S
Published: June 2010

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.
Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism
Authors: Møller S , Hansen M , Hillingsø J , Jensen J-E B , Henriksen J H
Published: June 2010

BACKGROUND

The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy.

AIMS

To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis.

METHODS

In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured.

RESULTS

Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism.

CONCLUSIONS

ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.
Bovine colostrum is a health food supplement which prevents NSAID induced gut damage
Authors: Playford R J , Floyd D N , Macdonald C E , Calnan D P , Adenekan R O , Johnson W , Goodlad R A , Marchbank T
Published: June 2010

BACKGROUND

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for arthritis but cause gastrointestinal injury. Bovine colostrum is a rich source of growth factors and is marketed as a health food supplement.

AIMS

To examine whether spray dried, defatted colostrum or milk preparations could reduce gastrointestinal injury caused by indomethacin.

METHODS

Effects of test solutions, administered orally, were examined using an indomethacin restraint rat model of gastric damage and an indomethacin mouse model of small intestinal injury. Effects on migration of the human colonic carcinoma cell line HT-29 and rat small intestinal cell line RIE-1 were assessed using a wounded monolayer assay system (used as an in vitro model of wound repair) and effects on proliferation determined using [3H]thymidine incorporation.

RESULTS

Pretreatment with 0.5 or 1 ml colostral preparation reduced gastric injury by 30% and 60% respectively in rats. A milk preparation was much less efficacious. Recombinant transforming growth factor β added at a dose similar to that found in the colostrum preparation (12.5 ng/rat), reduced injury by about 60%. Addition of colostrum to drinking water (10% vol/vol) prevented villus shortening in the mouse model of small intestinal injury. Addition of milk preparation was ineffective. Colostrum increased proliferation and cell migration of RIE-1 and HT-29 cells. These effects were mainly due to constituents of the colostrum with molecular weights greater than 30 kDa.

CONCLUSIONS

Bovine colostrum could provide a novel, inexpensive approach for the prevention and treatment of the injurious effects of NSAIDs on the gut and may also be of value for the treatment of other ulcerative conditions of the bowel.
Accuracy of screening for gastric cancer using serum pepsinogen concentrations
Authors: Kitahara F , Kobayashi K , Sato T , Kojima Y , Araki T , Fujino M A
Published: June 2010

BACKGROUND/AIMS

The characteristics of pepsinogen screening for gastric cancer were investigated to establish a suitable cut off point for identifying gastric cancer, using endoscopic diagnosis as the yardstick.

SUBJECTS/METHODS

Serum pepsinogen concentrations were measured in 5113 subjects who were also screened for gastric cancer by endoscopy. The cut off point for pepsinogen was determined using receiver operator characteristics curves.

RESULTS

The most suitable cut off point was a pepsinogen I concentration of less than 70 ng/ml and a ratio of pepsinogen I to pepsinogen II of less than 3.0. Using this cut off point, the sensitivity and specificity of pepsinogen screening for gastric cancer were 84.6% and 73.5% respectively. All cases of gastric cancer in patients with severe atrophic gastritis were detected. However, two of four cases of gastric cancer in patients with mild atrophic gastritis were overlooked. In subjects with mild atrophic gastritis, when gastric cancer arises within the fundic gland region, the size of the lesion determines whether it is possible to detect cancer by serum pepsinogen screening.

CONCLUSION

Pepsinogen screening has many advantages, including its suitability for combination with other screening methods because it is simple and inexpensive.
Microsatellite instability—a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer
Authors: Lamberti C , Kruse R , Ruelfs C , Caspari R , Wang Y , Jungck M , Mathiak M , Malayeri H R H , Friedl W , Sauerbruch T , Propping P
Published: June 2010

BACKGROUND

Clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is based on a typical family history. As molecular genetic testing is predominantly restricted to these families, gene carriers not meeting the clinical criteria may be missed.

AIMS

To examine the value of microsatellite instability (MSI) as a tool to increase the likelihood for uncovering a mismatch repair germline mutation in patients with colorectal cancer and to identify a genotype-phenotype relation in families with verified mutations.

METHODS

Systematic search for germline mutations (hMSH2 and hMLH1 genes) was performed in 96 patients: 57 fulfilled the Amsterdam criteria (group 1) and 12 the looser HNPCC criteria (group 2). Seventeen patients showed familial clustering of cancers (group 3) and 10 patients under 50 years had sporadic cancer (group 4), the latter of whom all exhibited MSI+ tumours.

RESULTS

A similar proportion of germline mutations was found in patients who fulfilled the clinical criteria of HNPCC and had MSI+ tumours (groups 1 and 2; 15/39) compared with patients who did not meet these clinical criteria but who had MSI+ tumours (groups 3 and 4; 8/27 patients). Affected relatives of patients with hMLH1 mutations showed a significantly higher frequency of colorectal cancer but a lower frequency of endometrium cancer than those with hMSH2 mutations.

CONCLUSIONS

MSI in tumour tissue is a useful criterion for selecting patients who should be tested for germline mutations in the mismatch repair genes hMSH2 and hMLH1 irrespective of their family history. Among carriers of hMSH2 mutations the tumour spectrum was broader than among carriers of hMLH1 mutations.
Quality of life in patients receiving home parenteral nutrition
Authors: Jeppesen P B , Langholz E , Mortensen P B
Published: June 2010

BACKGROUND/AIMS

Quality of life is an important determinant of the effectiveness of health technologies, but it has rarely been assessed in patients receiving home parenteral nutrition (HPN).

PATIENTS/METHODS

The non-disease specific sickness impact profile (SIP) and the disease specific inflammatory bowel disease questionnaire (IBDQ) were used on a cohort of 49 patients receiving HPN, and the results compared with those for 36 non-HPN patients with either anatomical (<200 cm) or functional (faecal energy excretion >2.0 MJ/day (∼488 kcal/day)) short bowel.

RESULTS

In the HPN patients the SIP scores were worse (higher) overall (17 (13)%v 8 (9)%) and with regard to physical (13 (15)% v 5 (8)%) and psychosocial (14 (12)% v 9 (11)%) dimensions and independent categories (20 (12)% v 9 (8)%) compared with the non-HPN patients (means (SD); all p<0.001). The IBDQ scores were worse (lower) in the HPN patients overall (5.0 (4.3–5.7)v 5.6 (4.8–6.2)) and with regard to systemic symptoms (3.8 (2.8–5.4) v 5.2 (3.9–5.9)) and emotional (5.3 (4.4–6.2) v5.8 (5.4–6.4)) and social (4.3 (3.4–5.5) v4.8 (4.5–5.8)) function (median (25–75%); all p<0.05), but only tended to be worse with regard to bowel symptoms (5.2 (4.8–6.1)v 5.7 (4.9–6.4), p = 0.08). HPN also reduced quality of life in patients with a stoma, whereas a stoma did not reduce quality of life among the non-HPN patients. Female HPN patients and HPN patients older than 45 scored worse.

CONCLUSION

Quality of life is reduced in patients on HPN compared with those with anatomical or functional short bowel not receiving HPN, and compares with that reported for patients with chronic renal failure treated by dialysis.
Screening SMAD1,SMAD2, SMAD3, andSMAD5 for germline mutations in juvenile polyposis syndrome
Authors: Bevan S , Woodford-Richens K , Rozen P , Eng C , Young J , Dunlop M , Neale K , Phillips R , Markie D , Rodriguez-Bigas M , Leggett B , Sheridan E , Hodgson S , Iwama T , Eccles D , Bodmer W , Houlston R , Tomlinson I
Published: June 2010

BACKGROUND AND AIMS

Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintestinal tumours. Recently, some JPS families were shown to harbour germline mutations in theSMAD4 (DPC4) gene, providing further evidence for the importance of the TGFβ signalling pathway in colorectal cancer. There remains, however, considerable, unexplained genetic heterogeneity in JPS. Other members of the SMAD family are excellent candidates for JPS, especiallySMAD2 (which, likeSMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when “knocked out” in mice),SMAD5, and SMAD1.

METHODS

SMAD1,SMAD2, SMAD3, andSMAD5 were screened for germline mutations in 30 patients with JPS and without SMAD4mutations.

RESULTS

No mutations were found in any of these genes. A G–A C89Y polymorphism with possible effects on protein function was found in SMAD3, but the frequencies of the G and A alleles did not differ between patients with JPS and controls.

CONCLUSIONS

It remains to be determined whether or not this polymorphism is involved in a minor predisposition to colorectal or other carcinomas.SMAD4 may be the only member of the SMAD family which causes JPS when mutant in the germline. The other genes underlying JPS remain to be identified.
Bile acid patterns in meconium are influenced by cholestasis of pregnancy and not altered by ursodeoxycholic acid treatment
Authors: Rodrigues C M P , Marín J J G , Brites D
Published: June 2010

BACKGROUND

Data on meconium bile acid composition in newborn babies of patients with intrahepatic cholestasis of pregnancy (ICP) are relatively scant, and changes that occur on ursodeoxycholic acid (UDCA) administration have not been evaluated.

AIMS

To investigate bile acid profiles in meconium of neonates from untreated and UDCA treated patients with ICP. Maternal serum bile acid composition was also analysed both at diagnosis and delivery to determine whether this influences the concentration and proportion of bile acids in the meconium.

PATIENTS/METHODS

The population included eight healthy pregnant women and 16 patients with ICP, nine of which received UDCA (12.5–15.0 mg/kg body weight/day) for 15±4 days until parturition. Bile acids were assessed in the meconium by gas chromatography-mass spectrometry and in maternal serum by high performance liquid chromatography.

RESULTS

Total bile acid and cholic acid concentrations in the meconium were increased (p<0.01) in newborns from patients with ICP (13.5 (5.1) and 8.4 (4.1) μmol/g respectively; mean (SEM)) as compared with controls (2.0 (0.5) and 0.8 (0.3) μmol/g respectively), reflecting the total bile acid and cholic acid levels in the maternal serum (r = 0.85 and r = 0.84, p<0.01). After UDCA administration, total bile acid concentrations decreased in the mother (∼3-fold, p<0.05) but not in the meconium. UDCA concentration in the meconium showed only a 2-fold increase after treatment, despite the much greater increase in the maternal serum (p<0.01). Lithocholic acid concentration in the meconium was not increased by UDCA treatment.

CONCLUSIONS

UDCA administration does not influence the concentration and proportion of bile acids in the meconium, which in turn are altered by ICP. Moreover, this beneficial treatment for the mother does not increase meconium levels of potentially toxic metabolites of UDCA such as lithocholic acid.
Oxidative Stress and DNA Methylation in Prostate Cancer
Authors: Donkena Krishna Vanaja , Young Charles Y. F. , Tindall Donald J.
Published: June 2010

The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin‐associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy.
Combined Piggyback Technique and Cavoportal Hemitransposition for Liver Transplant
Authors: Campsen Jeffrey , Kam Igal
Published: June 2010

Portal Vein thrombosis (PVT) increases the difficulty of liver transplant; however, it is not an absolute contraindication. Cavoportal hemitransposition (CPH) is an option for patients with complete PVT and no alternative collateral vein. Our center often performs the piggyback technique for the hepatic vein reconstruction, which allows for great access to the recipient vena cava in patients with known complete PVT that may need a CPH preformed to successfully restore flow to the portal system of the donor liver. We describe the use of the piggy-back technique to prepare the vena cava for possible CPH in patients with known complete PVT.
Accuracy Improvement by Boundary Conditions for Inertial Navigation
Authors: Nieminen Tuukka , Kangas Jari , Suuriniemi Saku , Kettunen Lauri
Published: June 2010

The term inertial navigation is often automatically associated with the term initial value problem. However, there are many applications where it is possible to end up with a boundary value problem (BVP) as well. We show that in case of a BVP, the finite element method that incorporates boundary conditions can be efficiently used to compute position and velocity estimates not prone to accumulation of errors. For further accuracy enhancements, a method of combining inertial measurements with additional constraints is proposed. This way, we can model sensor errors, known to limit the accuracy of the system. The capabilities of the proposed methods are demonstrated with real-life examples.
Microtubule-Disrupting Chemotherapeutics Result in Enhanced Proteasome-Mediated Degradation and Disappearance of Tubulin in Neural Cells
Authors: Huff Lyn M. , Sackett Dan L. , Poruchynsky Marianne S. , Fojo Tito
Published: June 2010

We sought to examine the effects of microtubule-targeting agents (MTA) on neural cells to better understand the problem of neurotoxicity, their principal side effect, and to possibly develop a model of clinical toxicity. Studies showed that microtubule-depolymerizing agents (MDA) not only disassembled microtubules in neural HCN2 cells but also led to rapid disappearance of tubulin, and that this was specific for MDAs. Tubulin levels decreased to 20% as early as 8 hours after adding vincristine, and to 1% to 30% (mean, 9.8 ± 7.6%; median of 7%) after 100 nmol/L vincristine for 24 hours. This disappearance was reversible. An increase in both glu-terminated and acetylated tubulin, markers of stable tubulin, preceded reaccumulation of soluble tubulin, suggesting a priority for stabilizing tubulin first as microtubules before replenishing the soluble pool. Similar results were shown with other MDAs. Furthermore, microtubule reassembly did not arise from a central focus but instead appeared to involve dispersed nucleation, as evidenced by the appearance of small, stable microtubule stubs throughout the cytoplasm. In contrast, experiments with four nonneural “normal” cell lines and four cancer cell lines resulted in microtubule destabilization but only modest tubulin degradation. Evidence for proteasome-mediated degradation was obtained by demonstrating that adding a proteasome inhibitor before vincristine prevented tubulin disappearance. In summary, MDAs lead to rapid disappearance of tubulin in neural but not in other normal or cancer cells. These results underscore the fine control that occurs in neural cells and may further our understanding of neurotoxicity following MDAs. Cancer Res; 70(14); 5870–9. ©2010 AACR.
Nrdp1-Mediated Regulation of ErbB3 Expression by the Androgen Receptor in Androgen-Dependent but not Castrate-Resistant Prostate Cancer Cells
Authors: Chen Liqun , Siddiqui Salma , Bose Swagata , Mooso Benjamin , Asuncion Alfredo , Bedolla Roble G. , Vinall Ruth , Tepper Clifford G. , Gandour-Edwards Regina , Shi XuBao , Lu Xiao-Hua , Siddiqui Javed , Chinnaiyan Arul M. , Mehra Rohit , deVere White Ralph W. , Carraway Kermit L. , Ghosh Paramita M.
Published: June 2010

Patients with advanced prostate cancer (PCa) are initially susceptible to androgen withdrawal (AW), but ultimately develop resistance to this therapy (castration-resistant PCa, CRPC). Here, we show that AW can promote CRPC development by increasing the levels of the receptor tyrosine kinase ErbB3 in androgen-dependent PCa, resulting in AW-resistant cell cycle progression and increased androgen receptor (AR) transcriptional activity. CRPC cell lines and human PCa tissue overexpressed ErbB3, whereas downregulation of ErbB3 prevented CRPC cell growth. Investigation of the mechanism by which AW augments ErbB3, using normal prostate-derived pRNS-1-1 cells, and androgen-dependent PCa lines LNCaP, PC346C, and CWR22 mouse xenografts, revealed that the AR suppresses ErbB3 protein levels, whereas AW relieves this suppression, showing for the first time the negative regulation of ErbB3 by AR. We show that AR activation promotes ErbB3 degradation in androgen-dependent cells, and that this effect is mediated by AR-dependent transcriptional upregulation of neuregulin receptor degradation protein-1 (Nrdp1), an E3 ubiquitin ligase that targets ErbB3 for degradation but whose role in PCa has not been previously examined. Therefore, AW decreases Nrdp1 expression, promoting ErbB3 protein accumulation, and leading to AR-independent proliferation. However, in CRPC sublines of LNCaP and CWR22, which strongly overexpress the AR, ErbB3 levels remain elevated due to constitutive suppression of Nrdp1, which prevents AR regulation of Nrdp1. Our observations point to a model of CRPC development in which progression of PCa to castration resistance is associated with the inability of AR to transcriptionally regulate Nrdp1, and predict that inhibition of ErbB3 during AW may impair CRPC development. Cancer Res; 70(14); 5994–6003. ©2010 AACR.
Tumor Antigen Epitopes Interpreted by the Immune System as Self or Abnormal-Self Differentially Affect Cancer Vaccine Responses
Authors: Ryan Sean O. , Turner Michael S. , Gariépy Jean , Finn Olivera J.
Published: June 2010

Epitope selection is an important consideration in the design of cancer vaccines, but factors affecting selection are not fully understood. We compared the immune responses to peptides and glycopeptides from the common human tumor antigen MUC1, a mucin that is coated with O-linked carbohydrates in its variable number of tandem repeats (VNTR) region. MUC1 expressed on tumor cells is characteristically underglycosylated, creating peptide and glycopeptide neoepitopes that are recognized by the immune system. The response to VNTR peptides is weaker in MUC1-transgenic mice (MUC1-Tg mice) than in wild-type (WT) mice, whereas the response to VNTR glycopeptides is equally strong in the two strains. Thus, glycopeptides seem to be recognized as foreign, whereas peptides, although immunogenic, are perceived as self. To explore this further, we generated MUC1 peptide– and glycopeptide–specific T-cell receptor transgenic mice and studied the function of their CD4 T cells when adoptively transferred into MUC1-Tg or WT mice. Peptide-specific T-cell precursors were not centrally deleted in MUC1-Tg mice and did not acquire a T regulatory phenotype. However, their response to the cognate peptide was reduced in MUC1-Tg mice compared with WT mice. In contrast, glycopeptide-specific CD4 T cells responded equally well in the two hosts and, when simultaneously activated, also enhanced the peptide-specific T-cell responses. Our data show that the immune system differentially recognizes various epitopes of tumor-associated antigens either as self or as foreign, and this controls the strength of antitumor immunity. This represents an important consideration for designing safe and effective cancer vaccines. Cancer Res; 70(14); 5788–96. ©2010 AACR.