bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults
Authors: Mann S D , Debinski H S , Kamm M A
Published: June 2010

Background—Chronic idiopathic intestinal pseudo-obstruction, a syndrome of ineffectual motility due to a primary disorder of enteric nerve or muscle, is rare.

Aims—To determine the clinical spectrum, underlying pathologies, response to treatments, and prognosis in a consecutive unselected group of patients.

Methods—Cross sectional study of all patients with clinical and radiological features of intestinal obstruction in the absence of organic obstruction, associated with dilated small intestine (with or without dilated large intestine), being actively managed in one tertiary referral centre at one time.

Results—Twenty patients (11 men and nine women, median age 43 years, range 22–67) fulfilled the diganostic criteria. Median age at onset of symptoms was 17 years (range two weeks to 59 years). Two patients had an autosomally dominant inherited visceral myopathy. Major presenting symptoms were pain (80%), vomiting (75%), constipation (40%), and diarrhoea (20%). Eighteen patients required abdominal surgery, and a further patient had a full thickness rectal biopsy. The mean time interval from symptom onset to first operation was 5.8 years. Histology showed visceral myopathy in 13, visceral neuropathy in three, and was indeterminate in three. In the one other patient small bowel motility studies were suggestive of neuropathy. Two patients died within two years of symptom onset, one from generalised thrombosis and the other from an inflammatory myopathy. Of the remaining 18 patients, eight were nutritionally independent of supplements, two had gastrostomy or jejunostomy feeds, and eight were receiving home parenteral nutrition. Five patients were opiate dependent, only one patient had benefited from prokinetic drug therapy, and five patients required formal psychological intervention and support.

Conclusions—In a referral setting visceral myopathy is the most common diagnosis in this heterogeneous syndrome, the course of the illness is usually prolonged, and prokinetic drug therapies are not usually helpful. Ongoing management problems include pain relief and nutritional support.
The effect of plasma low density lipoprotein apheresis on the hepatic secretion of biliary lipids in humans
Authors: Hillebrant C G , Nyberg B , Einarsson K , Eriksson M
Published: June 2010

Background—The liver is a key organ in the metabolism of cholesterol in humans. It is the only organ by which substantial amounts of cholesterol are excreted from the body, either directly as free cholesterol into the bile or after conversion to bile acids. The major part of cholesterol synthesis in the body occurs in the liver. Cholesterol is also taken up by the liver from plasma lipoproteins. The relative contributions of newly synthesised cholesterol and plasma lipoprotein cholesterol to bile acid synthesis and biliary cholesterol secretion, respectively, are not known in detail.

Aims—To determine how a rapid lowering of plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol influences the biliary secretion rates of cholesterol and bile acids in patients with cholesterol gallstones and complete biliary drainage. In this model with a completely interrupted enterohepatic circulation, the secretion of bile acids equals the new synthesis of bile acids in the liver.

Patients—Eight patients with common bile duct stones of cholesterol type undergoing conventional cholecystectomy and choledocholithotomy.

Methods—At operation a balloon occludable Foley catheter attached to a T tube was inserted into the bile duct with the balloon placed just past the distal limb of the T tube. The T tube was allowed to drain the bile externally. One week after the operation the Foley catheter balloon was inflated, creating complete biliary drainage. Twelve hours following the inflation plasma LDL apheresis was carried out for two hours. Bile was collected for 15 minute periods starting one hour before the apheresis and ending two hours after its termination. During the collection of bile, plasma lipids were analysed on several occasions.

Results—The plasma level of LDL cholesterol decreased by 26% from (mean (SEM)) 2.19 (0.29) to 1.63 (0.17) mmol/l during the LDL apheresis while high density lipoprotein (HDL) cholesterol in plasma was unaffected. During LDL apheresis apolipoprotein B containing lipoproteins bind to the column, causing a significant decrease of not only plasma LDL but also of VLDL cholesterol. The secretion rate of bile acids decreased significantly by 31% from 131 (38) to 90 (16) μmol/15 minutes (p=0.045). The output of phospholipids also decreased by 19%. The biliary secretion rate of cholesterol was not, however, affected by the plasma LDL apheresis.

Conclusions—The results suggest that, in patients with cholesterol gallstones and complete biliary drainage, lowering of plasma LDL and VLDL cholesterol reduces the biliary secretion rate—synthesis—of bile acids without affecting the biliary secretion rate of cholesterol.
Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole
Authors: Berstad A E , Hatlebakk J G , Maartmann-Moe H , Berstad A , Brandtzaeg P
Published: June 2010

Background—Helicobacter pylorigastritis may spread proximally in the stomach during profound acid inhibition.

Aims—To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole.

Patients and methods—Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15–73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland.

Results—Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p<0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pyloriinfected than in the uninfected group and increased further after treatment (p<0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment.

Conclusions—A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.
Abnormal mucus in cap polyposis
Authors: Buisine M P , Colombel J F , Lecomte-Houcke M , Gower P , Aubert J P , Porchet N , Janin A
Published: June 2010

Background—Cap polyposis is a rare disease characterised by mucoid and bloody diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate. The pathogenesis is not known.

Aims—To pour some light on cap polyposis pathogenesis, by examining the mucus of patients and analysing the expression of five mucin genes, MUC2, MUC3,MUC4, MUC5AC, and MUC5B.

Patient and methods—The study was performed on biopsy specimens taken from a patient with recurrent cap polyposis. Histochemical examination, electron microscopy, and mRNA in situ hybridisation were used.

Results—The mucus of cap polyposis differed in three respects from that of normal adult colon: abnormal ultrastructure of the mucus in the goblet cells, predominance of non-sulphated mucins, abnormal expression of the MUC4, MUC3, andMUC5AC genes.

Conclusions—Most of these abnormalities have been reported for other pathological situations, suggesting that the abnormalities observed in the mucus of this patient with cap polyposis are probably secondary phenomena rather than primary. However, the mucin abnormalities detected, which reflect deregulation of the expression of three apomucin genes, abnormal glycosylation, and abnormalities of the secretion process, are also probably involved in the clinical manifestations of cap polyposis.
Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man
Authors: Tack J , Coulie B , Wilmer A , Peeters T , Janssens J
Published: June 2010

Background—Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex.

Aims—To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1P receptors, on interdigestive motility in man.

Subjects and methods—In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred.

Results—Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin.

Conclusions—Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induct- ion of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.
Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study
Authors: Bearcroft C P , Perrett D , Farthing M J G
Published: June 2010

Background—Increased concentrations of 5-hydroxytryptamine (5-HT) can be detected in the systemic circulation after a meal and may be involved in the physiological control of gastrointestinal motility. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome (IBS).

Aim—To investigate the effect of a standard meal on plasma 5-HT and urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations in patients with diarrhoea predominant IBS and in healthy volunteers.

Methods—After an overnight fast, six volunteers and five patients with IBS were given a carbohydrate-rich meal. Blood and urine samples were taken before and for four hours after the meal. Platelet-poor plasma 5-HT and urinary 5-HIAA were analysed by reversed phase high performance liquid chromatography with fluorometric detection. 5-HIAA was expressed as a ratio with urinary creatinine concentration, which was measured by spectrophotometry.

Results—During the four hour postprandial period, 5-HT concentrations were significantly higher in patients with IBS than in healthy volunteers at 0.5 hours (p<0.05), 2 hours (p<0.05) and 2.5 hours (p<0.05). 5-HT was not detected in the plasma in the fasting state in patients or volunteers. Median peak 5-HT in patients with IBS (359 (198–796) nmol/l) was significantly greater than volunteers (83 (7–190)) (p<0.05). “Area under the curve” for 5-HT detection was greater for patients with IBS (317 (138–771)) than for healthy volunteers (51 (4–129); p<0.05).The duration of the 5-HT peak was significantly longer in patients with IBS (3 (1–3) hours) than in the healthy volunteers (1 (1–1) hours; p<0.01). Postprandial urinary median 5-HIAA values in controls (5.6 (5.5–5.8) μmol/mmol creatinine) and patients with IBS (3.0 (2.5–6.8) μmol/mmol creatinine) were not significantly different from preprandial values (controls: 5.9 (5.5–6.6) μmol/mmol creatinine; patients with IBS: (6.2 (2.4–9.3) μmol/mmol creatinine).

Conclusion—These findings indicate that there may be a difference in the way that 5-HT is released in patients with diarrhoea predominant IBS, and could suggest a possible role for 5-HT in the postprandial symptoms of these patients.
Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis
Authors: Kimura H , Hokari R , Miura S , Shigematsu T , Hirokawa M , Akiba Y , Kurose I , Higuchi H , Fujimori H , Tsuzuki Y , Serizawa H , Ishii H
Published: June 2010

Background—Increased production of reactive metabolites of oxygen and nitrogen has been implicated in chronic inflammation of the gut. The object of this study was to examine the magnitude and location of nitric oxide synthase (NOS) activity and peroxynitrite formation in the colonic mucosa of patients with ulcerative colitis in relation to the degree of inflammation.

Subjects—Thirty three patients with active ulcerative colitis (17 with mild or moderate inflammation, 16 with severe inflammation).

Methods—Inducible NOS activity was determined in the colonic mucosa by measuring the conversion ofl-arginine to citrulline in the absence of calcium. The localisation of NOS and nitrotyrosine immunoreactivity was assessed immunohistochemically using the labelled streptavidin biotin method.

Results—Inducible NOS activity increased in parallell with the degree of inflammation of the mucosa. Expression of inducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed by nitrotyrosine staining was frequently observed in the lamina propria of actively inflamed mucosa.

Conclusions—Nitric oxide and peroxynitrite formation may play an important role in causing irreversible cellular injury to the colonic mucosa in patients with active ulcerative colitis.
Interleukin 1β and tumour necrosis factor α inhibit acid secretion in cultured rabbit parietal cells by multiple pathways
Authors: Beales I L P , Calam J
Published: June 2010

Background—The cytokines interleukin 1β (IL-1β) and tumour necrosis factor α (TNF-α) are inhibitors of gastric acid secretion when administered systemically.

Aims—To investigate the inhibitory effect of IL-1β and TNF-α on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition.

Methods—Rabbit parietal cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation.

Results—IL-1β and TNF-α inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal effects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no effect on stimulation by dibutyryl-cAMP. Inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H2 or gastrin/CCKB receptors. Pertussis toxin abolished the inhibitory effects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory effects of TNF-α against all stimuli but only reduced the effects of IL-1β against histamine and forskolin stimulation.

Conclusions—IL-1β and TNF-α seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion.
Effect of increasing the fat content but not the energy load of a meal on gastro-oesophageal reflux and lower oesophageal sphincter motor function
Authors: Penagini R , Mangano M , Bianchi P A
Published: June 2010

Background—Although fatty foods are commonly considered detrimental in patients with reflux disease, no objective data exist that substantiate this belief.

Aims—To investigate the effect of fat on gastro-oesophageal reflux and lower oesophageal sphincter (LOS) motor activity.

Subjects—Thirteen healthy subjects and 14 patients with reflux disease.

Methods—Oesophageal pH, LOS, and oesophageal pressures were recorded for 180 minutes after a high fat (52% fat) and a balanced (24% fat) meal (both 3.18 MJ) on two different occasions. Eight controls and seven patients were studied in the recumbent position and the others in the sitting position.

Results—The percentage of time at pH less than 4 and the rate of reflux episodes were higher (p<0.01) in the patients than in the healthy subjects (mean 14.1% versus 1.7% and 4.4/h versus 0.8/h respectively), as was the percentage of transient LOS relaxations associated with reflux (62% versus 32%, p<0.01). The high fat meal did not increase the rate of reflux episodes nor exposure to oesophageal acid in either group regardless of body posture.The rate of transient LOS relaxations, their association with reflux, and basal LOS pressure were also unaffected.

Conclusions—Increasing fat intake does not affect gastro-oesophageal reflux or oesophagogastric competence for at least three hours after a meal.
Helicobacter pylori is killed by nitrite under acidic conditions
Authors: Dykhuizen R S , Fraser A , McKenzie H , Golden M , Leifert C , Benjamin N
Published: June 2010

Background—Due to the expression of urease,Helicobacter pylori is able to establish itself in the human stomach under acidic conditions. A novel host defence mechanism was recently proposed, suggesting that the formation of salivary nitrite in symbiosis with facultative anaerobic bacteria in the oropharynx, is aimed at enhancing the antimicrobial activity of gastric juice.

Aims—To investigate whether the addition of nitrite in physiological concentrations influences the resistance ofH pylori to acid.

Methods—H pylori cultured from fresh gastric biopsy specimens was exposed for 30 minutes to normal saline and to HCl/KCl buffer (0.2M) at pH 2 with urea (5 mM) added. The influence of potassium nitrite (50–1000 μmol/l) on bacterial survival was determined.

Results—Addition of nitrite (1 mM) to acidic solutions (pH 2) resulted in complete kill of H pyloriwithin 30 minutes exposure time whereas acid alone allowed the organism to survive (p<0.001). The antimicrobial effect of nitrite at pH 2 against H pylori was dose dependent and complete kill of organisms occurred at concentrations ⩾500 μmol/l.

Conclusion—Acidified nitrite has antibacterial activity against H pylori. This should prompt further research into the effect of salivary nitrite on the survival of H pylori in the human stomach.
Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol administration
Authors: Norton I D , Apte M V , Haber P S , McCaughan G W , Pirola R C , Wilson J S
Published: June 2010

Background—The mechanisms responsible for the initiation of alcoholic pancreatitis remain elusive. However, there is an increasing body of evidence that reactive oxygen species play a role in both acute and chronic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising enzyme) is one of the proposed pathways by which ethanol induces oxidative stress.

Aims—To determine whether CYP2E1 is present in the pancreas and, if so, whether it is inducible by chronic ethanol feeding.

Methods—Eighteen male Sprague-Dawley rats were pair fed liquid diets with or without ethanol as 36% of energy for four weeks. CYP2E1 levels were determined by western blotting of microsomal protein from both pancreas and liver. Messenger RNA (mRNA) levels for CYP2E1 were quantified using dot blots of total pancreatic RNA.

Results—CYP2E1 was found in the pancreas. Furthermore, the amount of CYP2E1 was greater in the pancreas of rats fed ethanol compared with controls (mean increase over controls 5.1-fold, 95% confidence intervals 2.4 to 7.7, p<0.02). In the liver, induction by ethanol of CYP2E1 was similar (mean increase over controls 7.9-fold, 95% confidence intervals 5.2 to 10.6, p<0.005). Pancreatic mRNA levels for CYP2E1 were similar in ethanol fed and control rats.

Conclusions—CYP2E1 is present in the rat pancreas and is inducible by chronic ethanol administration. Induction of pancreatic CYP2E1 is not regulated at the mRNA level. The metabolism of ethanol via CYP2E1 may contribute to oxidative stress in the pancreas during chronic ethanol consumption.
Effects of smoking on the urine excretion of oral51Cr EDTA in ulcerative colitis
Authors: Benoni C , Prytz H
Published: June 2010

Background—Smokers have a reduced risk and ex-smokers an increased risk of ulcerative colitis (UC). Stopping smoking often precedes onset and relapses. Smoking reduces the 24 hour urine excretion of oral chromium-51 labelled EDTA in healthy individuals.

Aims—To estimate the effects of smoking on the urine excretion of oral 51Cr EDTA in well characterised patients with UC.

Subjects—Sixteen smoking and 16 non-smoking patients with UC in remission were studied. The non-smokers had never smoked. Most were taking 5-aminosalicylic acid. No patient took steroids or immunosuppressants. The control group comprised 25 smoking healthy volunteers and 25 who had never smoked. The median cigarette consumption was equal in the patients and volunteers.

Methods—The 24 hour urine excretion of oral51Cr EDTA was measured and the results were correlated with smoking habits, number of cigarettes, and disease extent.

Results—Patients with UC had significantly higher 24 hour urine recoveries than healthy controls (p=0.04). This difference was more pronounced when patients who smoked were compared with healthy smokers (p=0.005) No significant differences were found when comparing non-smoking patients with non-smoking controls or when comparing smoking and non-smoking patients. Urine recoveries did not correlate with number of cigarettes or disease extent. Smoking was more prevalent in patients with a more limited disease extent (p=0.033).

Conclusions—Effects of smoking on the urine excretion of 51Cr EDTA in health were abolished by the presence of UC. The protective effects of smoking in established UC are not due to a moderating effect of smoking on intestinal permeability.
Outcome of orthotopic liver transplantation in patients with haemophilia
Authors: Gordon F H , Mistry P K , Sabin C A , Lee C A
Published: June 2010

Background—Many patients with haemophilia have developed cirrhosis or hepatocellular carcinoma due to transfusion acquired chronic viral hepatitis.

Aims—To assess the long term outcome of all haemophilic patients reported to have undergone orthotopic liver transplantation.

Methods—Transplant centres of patients identified by medical database search were contacted and survival data assessed by Kaplan-Meier analysis.

Results—Twenty six haemophilic men (median age 46 years, range 5–63 years) underwent orthotopic liver transplantation in 16 centres between 1982 and 1996. Indications for transplantation were hepatitis C cirrhosis (69%), hepatitis B with or without C cirrhosis (15%), viral hepatitis related hepatocellular carcinoma (12%), and biliary atresia (4%). Six patients (23%) were infected with human immunodeficiency virus (HIV). Postoperatively, the median time to normal clotting factor levels was 24 hours (range 0–48 hours) and exogenous clotting factors were stopped at a median of 24 hours (range 0–480 hours). Four patients (15%) had bleeding complications. The one and three year survival of HIV positive recipients (67% and 23%) was significantly poorer (p=0.0003) than that of HIV negative recipients (90% and 83%). Coagulopathy was cured in all patients surviving more than 12 days post-transplant. Six of the 20 patients (30%) with hepatitis C cirrhosis pretransplant had evidence of disease recurrence at a mean of nine months post-transplant.

Conclusions—Hepatitis C cirrhosis is the most common indication for orthotopic liver transplantation in patients with haemophilia. Transplantation results in long term cure of haemophilia but may be complicated by the effects of HIV infection or recurrent viral hepatitis.
Autoantibodies against subunits of pyruvate dehydrogenase and citrate synthase in a case of paediatric biliary cirrhosis
Authors: Melegh B , Skuta G , Pajor L , Hegedűs G , Sumegi B
Published: June 2010

In a newborn girl with a history of connatal liver damage, histological examination of a liver biopsy sample taken during the seventh week of life revealed incipient destruction of bile ducts. Very high titres of antimitochondrial antibodies were later detected in the plasma. As the hepatic injury tended towards fibrosis, the histological diagnosis became primary biliary cirrhosis. Autoantibodies against E1α, E2, and E3 subunits and protein X component of pyruvate dehydrogenase complex, and against citrate synthase were detected on western immunoblotting in a 1 in 1000 dilution of the patient’s serum. The patient died of her illness at 11 years of age. In liver specimens obtained at autopsy human immunoglobulin deposition was detected on the surface of almost all hepatic cells by immunohistology. As there is a physical and functional interaction between pyruvate dehydrogenase and citrate synthase within the mitochondria, the presence of autoantibodies against certain proteins in the patient suggests that in this form of the disease the molecular recognition and then the autoimmunisation process could be directed against a mitochondrial enzyme cluster containing both pyruvate dehydrogenase and citrate synthase.
Coexpression of gastrin and gastrin receptors (CCK-B and ΔCCK-B) in gastrointestinal tumour cell lines
Authors: McWilliams D F , Watson S A , Crosbee D M , Michaeli D , Seth R
Published: June 2010

Background—The peptide hormone gastrin is a recognised growth factor for gastrointestinal (GI) tumour cells. Carboxyamidated gastrins bind to the cell surface gastrin/cholecystokinin B (CCK-B) receptor which can be expressed as either a normal or a truncated isoform (ΔCCK-B).

Aims—To compare gastrin gene expression with ΔCCK-B and total CCK-B (both isoforms) gene expression in both GI and non-GI tract derived human tumour cell lines.

Methods—Total RNA was extracted and gene expression was assayed by the reverse transcription-polymerase chain reaction followed by Southern blotting and hybridisation with specific oligo probes.

Results—Gastrin was expressed by 5/5 gastric and 7/8 colorectal cell lines. Coexpression of gastrin CCK-B isoform was found in 80% of gastric and 75% of colorectal cell lines. Non-GI cell lines, with the exception of a lymphoblastic leukaemia cell line, showed no coexpression. The truncated receptor, ΔCCK-B, was shown in 3/5 gastric and 5/8 colorectal cell lines and was always coexpressed with gastrin.

Conclusions—The truncated gastrin receptor, ΔCCK-B, is coexpressed with gastrin in 8/13 GI tumour cell lines. Gastrin and CCK-B receptor isoforms may be involved in maintaining autocrine/paracrine growth pathways in GI cancer cells.
Imipramine decreases oesophageal pain perception in human male volunteers
Authors: Peghini P L , Katz P O , Castell D O
Published: June 2010

Background—Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed.

Aims—To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain.

Methods—Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1–3, 50 mg days 4–6, 75 mg days 7–12), with oesophageal perception studied on day 13.

Results—Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine.

Conclusion—Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect.
Responses to gastric distension in functional dyspepsia
Authors: Salet G A M , Samsom M , Roelofs J M M , van Berge Henegouwen G P , Smout A J P M , Akkermans L M A
Published: June 2010

Background—Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the compliance and adaptive relaxation of the proximal stomach contribute to the symptoms.

Aims—To investigate whether abnormal relaxation or adaptation of the proximal stomach during the interdigestive state and the postprandial phase could explain the symptoms of functional dyspepsia.

Subjects—Twelve volunteers and 12 patients with dysmotility-like functional dyspepsia were included in the study.

Methods—An electronic barostat was used to investigate adaptation to distension of the proximal stomach and accommodation in response to a liquid meal. Dyspeptic symptoms during distension and accommodation were assessed.

Results—When the subjects were in the fasting state, the pressure-volume curve showed slightly higher compliance in the dyspeptic patients (p<0.05). Patients not only had a higher score for nausea, bloating, and pain but also the increase in nausea and pain scores with intragastric pressure was higher than in volunteers (p<0.05). The increase in intragastric bag volume in response to a meal was significantly lower in patients (p<0.05). Both bloating and pain significantly increased in the patients (p<0.05), but not in the healthy volunteers.

Conclusions—Patients with functional dyspepsia show slightly higher compliance to mechanical distension. Their visceral perception of mechanical stress is enhanced. In contrast with the balloon distension, relaxation after a meal was less. Therefore the postprandial symptoms cannot be explained fully by greater global tension in the stomach wall, as assessed by the barostat technique. Visceral hypersensitivity plays a major role in the pathogenesis of the symptoms.
Non-cardiac, non-oesophageal chest pain: the relevance of psychological factors
Authors: Ho K Y , Kang J Y , Yeo B , Ng W L
Published: June 2010

Background—No cause has been determined for chest pain that is neither cardiac nor oesophageal in origin.

Aims—To compare the prevalence of lifetime psychiatric disorders and current psychological distress in three consecutive series of patients with chronic chest or abdominal pain.

Patients—Thirty nine patients with non-cardiac chest pain and no abnormality on oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour pH monitoring; 22 patients with non-cardiac chest pain having endoscopic abnormality, oesophageal dysmotility, and/or pathological reflux; and 36 patients with biliary colic.

Methods—The Diagnostic Interview Schedule and the 28 item General Health Questionnaire were administered to all patients.

Results—Patients with non-cardiac chest pain and no upper gastrointestinal disease had a higher proportion of panic disorder (15%), obsessive-compulsive disorder (21%), and major depressive episodes (28%) than patients with gallstone disease (0%, p<0.02; 3%, p<0.02; and 8%, p<0.05, respectively). In contrast, there were no differences between patients with non-cardiac chest pain and upper gastrointestinal disease and patients with gallstone disease in any of the DSM-111 defined lifetime psychiatric diagnoses. Using the General Health Questionnaire, 49% of patients with non-cardiac chest pain without upper gastrointestinal disease scored above the cut off point (that is, more than 4), which was considered indicative of non-psychotic psychiatric disturbance, whereas only 14% of patients with gallstones did so (p<0.005). The proportions of such cases were however similar between patients with non-cardiac chest pain and upper gastrointestinal disease (27%) and patients with gallstones.

Conclusions—Psychological factors may play a role in the pathogenesis of chest pain that is neither cardiac nor oesophagogastric in origin.
Lipids infused into the jejunum accelerate small intestinal transit but delay ileocolonic transit of solids and liquids
Authors: Hammer J , Hammer K , Kletter K
Published: June 2010

Background—Various nutrients are known to alter small intestinal motility patterns although their effect on transit of fluids and solids in man is not clear.

Aims—To determine small intestinal transit of solids and liquids during perfusion with lipids, protein, and non-energy solutions.

Methods—Twenty eight healthy volunteers received a jejunal infusion (1 ml/ minute for 30 minutes) of one of four solutions: a lipid or a protein solution (4.18 J/ml), a non-absorbable electrolyte solution containing polyethylene glycol, or 0.9% sodium chloride. As solid phase marker 1 g of amberlite resin pellets labelled with 111InCl3 was added;99mTc DTPA was used as a fluid phase marker. Images were obtained on a gamma camera at 10 minute intervals for four hours or until all radiolabel was detected in the colon.

Results—Intestinal transit of solids and liquids from the duodenojejunal junction to the caecum was simultaneous, and independent of the energy content of the solution infused. Lipid infusion accelerated transit through the small intestine but delayed transport of chyme along the ileocolonic junction. After protein small intestinal transit was slowest; ileocolonic transit on the other hand was fastest with protein. Transit of the non-energy solutions was in between that of the nutrient solutions.

Conclusions—Transit times through the small intestine and the ileocolonic junction were influenced by the luminal contents. In the small intestine fat induced significantly faster transit compared with proteins, but delayed ileocolonic transit. Once in the small intestine, solids and liquids transit the small bowel together, independent of the luminal content.
Five genetic markers in the interleukin 1 family in relation to inflammatory bowel disease
Authors: Stokkers P C F , van Aken B E , Basoski N , Reitsma P H , Tytgat G N J , van Deventer S J H
Published: June 2010

Background—An imbalance between the proinflammatory cytokine interleukin 1β (IL-1β) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has been postulated as a pathogenic factor in inflammatory bowel disease (IBD).

Aims—To study allelic frequencies of novel polymorphisms in the genes for IL-1β and IL-1ra in patients with IBD and to assess the relation between ex vivo cytokine production and allelic variants of the IL-1β and IL-1ra genes.

Subjects—Two hundred and seventy healthy controls, 74 patients with ulcerative colitis (UC), 72 with Crohn’s disease (CD), 40 with primary sclerosing cholangitis for the allelic frequencies, and 60 healthy individuals for the ex vivo stimulation test.

Methods—Genotyping was performed by polymerase chain reaction and subsequent cleavage with specific endonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novel restriction fragment length polymorphisms (RFLPs) in the genes for IL-1ra and IL-1β.

Results—No significant differences were found in the allelic frequencies or allele carriage rates of the markers in the IL-1β and IL-1ra genes between CD, UC, and healthy controls. No association between the genetic markers and cytokine production levels was observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly more frequently (35.2% in UC versus 71.1% in controls).

Conclusions—UC is associated with carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs. However, it could not be confirmed whether the association reflects a pathogenic mechanism underlying UC.
Bromelain protects piglets from diarrhoea caused by oral challenge with K88 positive enterotoxigenicEscherichia coli
Authors: Chandler D S , Mynott T L
Published: June 2010

Background—K88 positive enterotoxigenicEscherichia coli (K88+ ETEC) is an important cause of diarrhoea in young piglets. K88+ ETEC pathogenesis relies on attachment to specific glycoprotein receptors located on the intestinal mucosa. Proteolytic treatment of these receptors in vitro and in vivo prevents attachment of K88+ETEC to piglet small intestines and may be of clinical use to prevent K88+ ETEC pathogenesis.

Aims—To determine whether bromelain, a proteolytic extract obtained from pineapple stems, would protect piglets against K88+ ETEC diarrhoea and to confirm and extend earlier findings on the effects of bromelain on K88+ ETEC receptors in vivo.

Methods—Bromelain (0, 12.5, or 125 mg) was orally administered to just weaned piglets for 10 days. One day following commencement of bromelain treatment, piglets were challenged with K88+ ETEC (5 × 1010 K88ac:0149) for seven days. Intestinal contents from unchallenged piglets were obtained via an intestinal fistula, and tested for their ability to bind K88+ ETEC before and after bromelain treatment.

Results—Both doses of bromelain were successful in reducing the incidence of K88+ ETEC diarrhoea and protected piglets from life threatening disease. Bromelain treated pigs also had significantly increased weight gain compared with untreated pigs. Bromelain only temporarily inhibited K88+ ETEC receptor activity, with receptor activity being regenerated 30 hours following treatment, consistent with the regeneration of new enterocytes.

Conclusion—Results show that bromelain can temporarily inactivate ETEC receptors in vivo and protect against ETEC induced diarrhoea. Bromelain may therefore be an effective prophylaxis against ETEC infection.
Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease
Authors: Noguchi M , Hiwatashi N , Liu Z , Toyota T
Published: June 2010

Background—Tumour necrosis factor (TNF) α and TNF-β are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD).

Aims—To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD.

Methods—The secretion of TNF-α, TNF-β, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD.

Results—Spontaneous secretion of TNF-α in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-β was higher in patients with Crohn’s disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-α production correlated with severity of disease.

Conclusions—Results showed enhanced secretion of TNF-α but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.
A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits
Authors: Osman M O , Kristensen J U , Jacobsen N O , Lausten S B , Deleuran B , Deleuran M , Gesser B , Matsushima K , Larsen C G , Jensen S L
Published: June 2010

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.

Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.

Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.

Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.

Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.
Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat
Authors: Poulsen S S , Thulesen J , Nexø E , Thim L
Published: June 2010

Background—Trefoil peptides are secreted by mucus producing cells in the gastrointestinal tract and are supposed to be involved in oligomerisation processes of the mucin glycoproteins in the lumen. Endocrine functions have also been suggested.

Aims—To target possible binding sites for iodine-125 labelled porcine spasmolytic polypeptide (pSP) in an in vivo rat model.

Methods—125I-pSP was given by intravenous injection to female Spraque-Dawley rats. The distribution of 125I-pSP was assessed by gamma counting of samples of organs and by autoradiography of paraffin wax embedded sections. The degradation of 125I-pSP was studied by trichloroacetic acid precipitation, and the saturability of binding by administration of excess unlabelled peptide.

Results—125I-pSP was taken up in the kidneys and the gastrointestinal tract and was excreted almost unmetabolised in the urine. In the stomach, it could be displaced by unlabelled pSP in a dose dependent manner. Autoradiography showed grains in mucous neck cells, parietal cells, the mucus layer, and the pyloric glands of the stomach; in Brunner’s glands and the Paneth cells in the small intestine; and in cells in the lower part of the crypts in the colon.

Conclusions—125I-pSP from the circulatory system is taken up by mucus producing cells in the gastrointestinal tract. The binding can be displaced by non-radioactive pSP, suggesting the presence of a receptor.
Evidence for a lipid specific effect in nutrient induced human proximal gastric relaxation
Authors: McLaughlin J T , Troncon L E A , Barlow J , Heggie L J , Thompson D G
Published: June 2010

Background/Aim—The presence of lipid in the upper gut is able to modify gastrointestinal motor performance, but its influence on the relaxation of the human stomach, which is known to modify gastric emptying, remains incompletely understood. The relaxation of the proximal stomach in response to various lipid concentrations was therefore studied in healthy volunteers. Since the observed effects could be mediated through osmolality or energy sensitive pathways, the effects of equicaloric and equiosmolar non-lipid solutions were also determined.

Methods—The tone of the proximal stomach was measured during stepwise inflation of a non-compliant bag sited in the proximal stomach, both before and after a test meal was delivered intragastrically. Iso-osmolar lipid emulsions were diluted in iso-osmolar saline at concentrations of 1.25, 2.5, 5, 10, and 20%. NaCl solutions at osmolalities of 300, 600, 1200 and 2400 mmol/kg and glucose solutions of 836 and 3344 kJ/l were also given.

Results—All lipid meals of 2.5% or greater concentration induced a reduction in gastric tone in a non-dose-dependent manner, responses to 5% lipid (median (range) 74 (62–92)%) being similar to those to 20% lipid (80 (55–83)%; p>0.05). No relaxation was elicited by isocaloric glucose. NaCl only consistently caused relaxation at 2400 mmol/kg.

Conclusion—Lipid meals reduce human proximal gastric tone by a lipid specific mechanism, independently of their energy content or osmolality.
Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease
Authors: Grove J , Daly A K , Burt A D , Guzail M , James O F W , Bassendine M F , Day C P
Published: June 2010

Background—Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE,has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder).

Aim—To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in predisposition to advanced alcoholic liver disease.

Methods—TheHFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0–4) on biopsy specimens from fibrotic/cirrhotic patients with and withoutHFE mutations matched for age and sex.

Results—Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients’ chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (>grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls.

Conclusions—Possession of a single copy of either of the two HFEmutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.
Two way push videoenteroscopy in investigation of small bowel disease
Authors: Bouhnik Y , Bitoun A , Coffin B , Moussaoui R , Oudghiri A , Rambaud J C
Published: June 2010

Aims—To evaluate the diagnostic yield and safety of a new push type videoenteroscope (PVE) for diagnosis of small bowel disease.

Methods—Three hundred and thirteen patients were referred for one or two way PVE from December 1993 to June 1996. Indications for PVE were: an unexplained iron deficiency anaemia with or without clinically evident gastrointestinal bleeding; or a complementary investigation for suspected small bowel disease, after a small bowel barium follow through (SBBFT) considered as normal or abnormal, but without a definite diagnosis.

Results—A jejunoscopy and a retrograde ileoscopy were carried out in 306 and 234 patients, respectively. In patients with isolated anaemia (n=131) and those with clinically evident gastrointestinal bleeding associated anaemia (n=72), PVE provided a diagnosis in 26 (19.8%) and 22 (30.5%) cases, respectively. Lesions found were located in the jejunoileum in 30 (14.7%) patients and in the gastroduodenum or the colon in 18 (8.8%) patients—that is, within the reach of the conventional gastroscope/colonoscope. In patients with normal (n=54) or abnormal (n=56) SBBFT, PVE provided a diagnosis in 17 (31%) and 27 (48%) cases, respectively. In 25% of cases, the abnormal appearance of SBBFT was not confirmed. The site of the radiological abnormality was not reached in 27% of cases. Lesions were located at the jejunum and the ileum in 59 (64%) and 33 (36%) cases, respectively.

Conclusions—PVE is useful in around 30% of cases of unexplained anaemia or after an SBBFT which failed to provide an accurate aetiological diagnosis. Use of retrograde videoenteroscopy increases diagnostic yield by one third.