bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that nitric oxide mechanisms regulate small intestinal motility in humans
Authors: Russo A , Fraser R , Adachi K , Horowitz M , Boeckxstaens G 
Published: June 2010

BackgroundNon-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition may be important in the regulation of cyclical fasting small intestinal motility.AimsTo evaluate the role of NO mechanisms in the regulation of fasting small intestinal motor activity in humans using a specific NO synthase inhibitor,NG-monomethyl-l-arginine ( l-NMMA).MethodsIn seven healthy male volunteers, duodenal and jejunal pressures were measured for four hours with a nine lumen manometric catheter. Volunteers attended on four separate days on which they received an intravenous infusion of either saline or l-NMMA (0.5, 2, or 4 mg/kg/h) in random order. Intravenous infusions began 10 minutes after completion of phase III of the migrating motor complex (MMC).ResultsThe first episode of phase III activity occurred earlier after infusion of 2 and 4 mg/kg/h l-NMMA than after infusion of 0.5 mg/kg/hl-NMMA or saline (mean (95% confidence interval) 52 (36–68) and 57 (18–97) v 116 (69–193) and 145 (64–226) minutes respectively) with a resultant MMC cycle length of 82 (59–105) and 86 (46–126) v 132 (49–198) and 169 (98–240) minutes respectively. The total number of phase III activities during the four hour recording was increased (p<0.05) by l-NMMA at a dose of 4 mg/kg/h (2 (1–3)) but not at 2 mg/kg/h (1.5 (1–2)) or 0.5 mg/kg/h (1.3 (1–2)) compared with saline (1.3 (0.6–2)). l-NMMA had no effect on the duration, velocity, number of contractions per minute, length of migration, or site of origin of phase III of the MMC. The duration of phase I activity was shorter (p<0.05) with 4 mg/kg/hl-NMMA than with saline (12 (1–23)v 31 (19–44) minutes).ConclusionsThese observations suggest that NO mechanisms play a role in the regulation of fasting small intestinal motor activity in humans.
Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time
Authors: Gielkens H A J , van den Biggelaar A , Vecht J , Onkenhout W , Lamers C B H W , Masclee A A M 
Published: June 2010

BackgroundPatients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying.AimsTo investigate whether intravenous amino acids also influence antroduodenal motility.MethodsEight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test.ResultsDCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control.ConclusionsSeparate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.
Structure of cag pathogenicity island in Japanese Helicobacter pyloriisolates
Authors: Maeda S , Yoshida H , Ikenoue T , Ogura K , Kanai F , Kato N , Shiratori Y , Omata M 
Published: June 2010

BACKGROUNDcagpathogenicity island (PAI) is reported to be a major virulence factor of Helicobacter pylori.AIMTo characterisecagA and the cagPAI in Japanese H pylori strains.METHODSH pylori isolates from Japanese patients were evaluated for CagA by immunoblot, for cagA transcription by northern blot, and for cagA and 13 othercag PAI genes by Southern blot.cagA negative strains from Western countries were also studied. Induction of interleukin-8 secretion from gastric epithelial cells was also investigated.RESULTSAll Japanese strains retained cagA. Fifty nine of 63 (94%) strains had all the cag PAI genes. In the remaining four, cag PAI was partially deleted, lacking cagA transcripts and not producing CagA protein. Details of the PAI of these strains were checked; three lacked cagB tocagQ (cagI) and continuously cagS tocag13 (cagII), and the remaining one lacked cagB tocag8. WesterncagA negative strains completely lackedcag PAI includingcagA. Nucleotide sequence analysis in one strain in which the cag PAI was partially deleted showed that the partial deletion contained 25 kb ofcag PAI and thecagA promoter. Interleukin-8 induction was lower with the cag PAI partial deletion strains than with the intact ones. All Japanesecag PAI deleted strains were derived from patients with non-ulcer dyspepsia, whereas 41 of 59 (70%) CagA-producing strains were from patients with peptic ulcers or gastric cancer (p<0.05).CONCLUSIONSMost Japanese H pylori strains had the intactcag PAI. However, some lacked most of thecag PAI in spite of the presence ofcagA. Thus the presence of thecagA gene is not an invariable marker ofcag PAI related virulence in Japanese strains.
Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease
Authors: Dunn-Walters D K , Boursier L , Hackett M , Spencer J 
Published: June 2010

BACKGROUNDUlcerative colitis is an inflammatory disease of the colonic and rectal mucosa. Autoantibodies have been observed in ulcerative colitis which may have a role in the pathogenesis of the disease. Evidence also suggests that there is an hereditary predisposition towards the disease, although no individual genes have been identified.AIMSThis is a pilot study of immunoglobulin heavy chain genes (IgH) in ulcerative colitis to determine whether they have any particular genetic characteristics which may lead to a better understanding of the disease aetiology.SUBJECTSColonic or rectal tissue was obtained from five children with ulcerative colitis. Tissue was also obtained from five children with Crohn’s disease and five children who did not have inflammatory bowel disease as controls.METHODSB cells and IgD+ B cells were identified by immunohistochemistry on frozen sections. Areas of lamina propria containing plasma cells, and areas of IgD+ B cells were microdissected. The immunoglobulin genes were PCR amplified, cloned, and sequenced. Sequences were analysed for content of somatic mutations and composition of heavy chain.RESULTSAn increase in the use of JH6 and DXP′1, and a decrease in the use of JH4, gene segments in immunoglobulin genes from lamina propria plasma cells, and from virgin IgD+ B cells, was found in patients with ulcerative colitis. These biases were not present in the control groups.CONCLUSIONSThere is a fundamental difference in the immunoglobulin genes from patients with ulcerative colitis. Whether this is caused by a difference in content of immunoglobulin gene segments in the germline or a difference in the recombination mechanism is not known.
Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis
Authors: Van Klinken B J-W , Van der Wal J-W G , Einerhand A W C , Büller H A , Dekker J 
Published: June 2010

BACKGROUNDDecreased synthesis of the predominant secretory human colonic mucin (MUC2) occurs during active ulcerative colitis.AIMSTo study possible alterations in mucin sulphation and mucin secretion, which could be the cause of decreased mucosal protection in ulcerative colitis.METHODSColonic biopsy specimens from patients with active ulcerative colitis, ulcerative colitis in remission, and controls were metabolically labelled with [35S]-amino acids or [35S]-sulphate, chase incubated and analysed by SDS-PAGE, followed by quantitation of mature [35S]-labelled MUC2. For quantitation of total MUC2, which includes non-radiolabelled and radiolabelled MUC2, dot blotting was performed, using a MUC2 monoclonal antibody.RESULTSBetween patient groups, no significant differences were found in [35S]-sulphate content of secreted MUC2 or in the secreted percentage of either [35S]-amino acid labelled MUC2 or total MUC2. During active ulcerative colitis, secretion of [35S]-sulphate labelled MUC2 was significantly increased twofold, whereas [35S]-sulphate incorporation into MUC2 was significantly reduced to half.CONCLUSIONSDuring active ulcerative colitis, less MUC2 is secreted, because MUC2 synthesis is decreased while the secreted percentage of MUC2 is unaltered. Furthermore, sulphate content of secreted MUC2 is unaltered by a specific compensatory mechanism, because sulphated MUC2 is preferentially secreted while sulphate incorporation into MUC2 is reduced.
The role of psychological and biological factors in postinfective gut dysfunction
Authors: Gwee K-A , Leong Y-L , Graham C , McKendrick M W , Collins S M , Walters S J , Underwood J E , Read N W 
Published: June 2010

BACKGROUNDBoth psychological and physiological disturbances have been implicated in the aetiopathogenesis of irritable bowel syndrome (IBS).AIMSTo investigate how the psychological factors act, and the involvement of infective and physiological factors.METHODSConsecutive patients hospitalised for gastroenteritis reported life events for the previous 12 months, and past illness experiences on standardised questionnaires. They also completed psychometric questionnaires for anxiety, neuroticism, somatisation, and hypochondriasis. In some patients, rectal biopsy specimens were obtained during the acute illness and at three months postinfection.RESULTSNinety four patients completed all questionnaires: 22 patients were diagnosed with IBS after their gastroenteritis (IBS+), and 72 patients returned to normal bowel habits (IBS−). IBS+ patients reported more life events and had higher hypochondriasis scores than IBS− patients. The predictive value of the life event and hypochondriasis measures was highly significant and independent of anxiety, neuroticism, and somatisation scores, which were also elevated in IBS+ patients. Rectal biopsy specimens from 29 patients showed a chronic inflammatory response in both IBS+ and IBS− patients. Three months later, specimens from IBS+ patients continued to show increased chronic inflammatory cell counts but those from IBS− patients had returned to normal levels. IBS+ and IBS− patients exhibited rectal hypersensitivity and hyper-reactivity and rapid colonic transit compared with normal controls, but there were no significant differences between IBS+ and IBS− patients for these physiological measurements.CONCLUSIONPsychological factors most clearly predict the development of IBS symptoms after gastroenteritis but biological mechanisms also contribute towards the expression of symptoms.
Predicting bone loss following orthotopic liver transplantation
Authors: Crosbie O M , Freaney R , McKenna M J , Curry M P , Hegarty J E 
Published: June 2010

BACKGROUNDHepatic osteodystrophy occurs in the majority of patients with advanced chronic liver disease with the abnormalities in bone metabolism accelerating following orthotopic liver transplantation (OLT).AIMSTo examine changes in bone mineral density (BMD) following OLT and to investigate factors that lead to bone loss.METHODSTwelve patients had BMD (at both the lumbar spine (LS) and femoral neck (FN)) and biochemical markers measured preoperatively and for 24 months following OLT.RESULTSBMD was low in 75% of patients prior to OLT and decreased significantly from baseline at the LS at three months and the FN at six months. BMD began to increase thereafter at both sites, approaching baseline values at the LS by 12 months. Bone formation markers, osteocalcin and procollagen type I carboxy propeptide, decreased immediately post-OLT, with a concomitant increase seen in the resorption markers pyridinoline and deoxypyridinoline. This resulted in a negative uncoupling index early post-OLT, that rebounded to positive values after six months. There was a significant correlation between the change in the uncoupling index between six and three months which preceded the increase in BMD at 12 months. The decrease in BMD recorded early post-OLT correlated with vitamin D levels at three months.CONCLUSIONSResults suggest that increased resorption and inadequate formation are the major contributors to additional bone loss following OLT. Non-invasive biochemical markers precede later changes in BMD in this patient group following OLT and may have a role in investigating and planning intervention strategies to prevent bone loss in future studies.
Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa
Authors: Wedemeyer J , Lorentz A , Göke M , Meier P N , Flemming P , Dahinden C A , Manns M P , Bischoff S C 
Published: June 2010

BACKGROUNDThe β chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils.AIMSTo investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa.PATIENTSForty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined.METHODSImmunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1β, IL-6, and tumour necrosis factor α (TNF-α) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively.RESULTSIn tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected.CONCLUSIONSOur data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.
Notable postnatal alterations in the myenteric plexus of normal human bowel
Authors: Wester T , O’Briain D S , Puri P 
Published: June 2010

BACKGROUNDNitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung’s disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group.AIMSTo determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood.METHODSSpecimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated.RESULTSThe myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus.CONCLUSIONSThe notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.
Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans
Authors: Bouras E P , Camilleri M , Burton D D , McKinzie S 
Published: June 2010

BACKGROUNDPrucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro.AIMSTo evaluate the effects of prucalopride on gastrointestinal and colonic transit.METHODSA validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0.5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours.RESULTSThere were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0.12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects.CONCLUSIONPrucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation.
Cost comparison of predictive genetic testing versus conventional clinical screening for familial adenomatous polyposis
Authors: Bapat B , Noorani H , Cohen Z , Berk T , Mitri A , Gallie B , Pritzker K , Gallinger S , Detsky A S 
Published: June 2010

BACKGROUNDMutations of theAPC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome.AIMSTo conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer.METHODSAll direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model.RESULTSThe baseline analysis predicted that screening a prototype FAP family would cost $4975/£3109 by molecular testing and $8031/£5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if theAPC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/£4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives.CONCLUSIONSIn FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be non-carriers.
Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt
Authors: Huonker M , Schumacher Y O , Ochs A , Sorichter S , Keul J , Rössle M 
Published: June 2010

BACKGROUNDA portosystemic stent shunt may impair cardiac function and haemodynamics.AIMSTo investigate the effects of a transjugular intrahepatic portosystemic shunt (TIPS) on cardiac function and pulmonary and systemic circulation in patients with alcoholic cirrhosis.PATIENTS/METHODS17 patients with alcoholic cirrhosis and recent variceal bleeding were evaluated by echocardiography and catheterisation of the splanchnic and pulmonary circulation before and after TIPS. The period of catheter measurement was extended to nine hours in nine of the patients. The portal vein was investigated by Doppler ultrasound before and nine hours after TIPS.RESULTSBaseline echocardiography showed the left atrial diameter to be slightly increased and the left ventricular volume to be in the upper normal range. Nine hours after TIPS, the left atrial diameter and left ventricular end diastolic volume were increased (by 6% (p<0.01) and 7% (p<0.01) respectively); end systolic volume had not changed significantly. Invasive measurements showed a sharp increase in right atrial pressure (by 101%; p<0.01), mean pulmonary artery pressure (by 92%; p<0.01), pulmonary capillary wedge pressure (by 111%; p<0.01), and cardiac output (8.1 (1.6) to 11.9 (2.4) l/min; p<0.01). Systemic vascular resistance decreased (824 (242) to 600 (265) dyn·s·cm−5 p<0.01), and total pulmonary resistance increased (140 (58.5) to 188 (69.5) dyn·s·cm−5; p<0.05). Total pulmonary resistance (12%; NS), cardiac output (1.4 l/min; p<0.05), and portal vein blood flow (1.4 l/min; p<0.05) remained elevated for nine hours after TIPS in the subgroup. Portoatrial pressure gradient (43%; p<0.05), portohepatic vascular resistance (72%; p<0.05), and systemic vascular resistance (27%; p<0.01) were consistently reduced.CONCLUSIONSThe increase in the left atrial diameter, the pulmonary capillary wedge pressure, and total pulmonary resistance observed after the TIPS procedure reflected diastolic dysfunction of the hyperdynamic left ventricle in patients with alcoholic cirrhosis. The haemodynamic effects of the portosystemic stent shunt itself on the splanchnic circulation seem to be mainly responsible for the further decrease in systemic vascular resistance. TIPS may unmask a coexisting preclinical cardiomyopathy in patients with alcoholic cirrhosis and portal hypertension.