bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes
Authors: Carol M , Lambrechts A , Van Gossum A , Libin M , Goldman M , Mascart-Lemone F 
Published: June 2010

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.
The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock
Authors: Oldner A , Wanecek M , Goiny M , Weitzberg E , Rudehill A , Alving K , Sollevi A 
Published: June 2010

Background—Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock.Aims—To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock.Methods—In 16 anaesthetised pigs, central and regional haemodynamics were monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later.Results—Endotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaffected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial Pco2 gap. The mucosal-portal vein Pco2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan.Conclusion—Bosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock.
Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis
Authors: Tsai K , Wang S-S , Chen T-S , Kong C-W , Chang F-Y , Lee S-D , Lu F-J 
Published: June 2010

Background—Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation.Aims—To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis.Patients and methods—Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, α tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis.Results—In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in α tocopherol were not great except in one case with poor prognosis. Differences between severe and mild acute pancreatitis were significant (p<0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease.Conclusions—Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment.
Transcatheter coil embolotherapy: a safe and effective option for major colonic haemorrhage
Authors: Nicholson A A , Ettles D F , Hartley J E , Curzon I , Lee P W R , Duthie G S , Monson J RT 
Published: June 2010

Background—The management of major colonic bleeding is problematic. A proportion of patients require emergency surgery which is associated with high morbidity and mortality. Percutaneous embolotherapy, previously considered a high risk procedure in the colon, may provide an alternative treatment in this group of patients.Aims—To assess the safety and efficacy of embolotherapy in the treatment of life threatening colonic haemorrhage.Patients and methods—Thirty eight patients with fresh haemorrhage per rectum were referred for surgery because of failed conservative treatment. All underwent angiography; in 14 a bleeding site or vascular abnormality was detected. A coaxial catheter was directed to the most distal bleeding artery and this was embolised with platinum coils.Results—Detection of a bleeding site correlated with haemodynamic stability at the time of angiography (r=1 for a systolic blood pressure less than 100 mm Hg). Bleeding sites or vascular abnormalities were detected and embolised in 14 patients (37%). In 12/14 there was immediate and sustained haemodynamic improvement; two continued to bleed and required emergency hemicolectomy (14%). Three developed ischaemic complications (21.4%); these were managed conservatively and required no intervention. The 30 day mortality was 7.1% in the embolotherapy group and 10.5% in the overall group of 38 patients.Conclusion—Colonic embolotherapy for life threatening haemorrhage is an effective, relatively safe procedure with a low incidence of major complications. Its use depends on the identification of a focal bleeding point or vascular abnormality, which in turn depends on the haemodynamic stability of the patient at the time of angiography.
Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer
Authors: Ilyas M , Hao X-P , Wilkinson K , Tomlinson I P M , Abbasi A M , Forbes A , Bodmer W F , Talbot I C 
Published: June 2010

Aims—To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery.Methods—Sixty six cases of Dukes’ B colorectal carcinoma were studied. All tumours were moderately differentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls).Results—A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2–9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6–10) in those without recurrence; p=0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p=0.04 in each case). There was no association between p53 staining and tumour recurrence.Conclusion—Results suggest that, when controlled for differentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making.
Prognostic factors in patients with endocrine tumours of the duodenopancreatic area
Authors: Madeira I , Terris B , Voss M , Denys A , Sauvanet A , Flejou J-F , Vilgrain V , Belghiti J , Bernades P , Ruszniewski P 
Published: June 2010

Background—The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP.Patients/Methods—Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis.Results—Twenty eight patients (34%) died within a median of 17 months (range 1–110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p<0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size ⩾3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p<0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively.Conclusion—Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.
Microprocessor controlled movement of liquid gastric content using sequential neural electrical stimulation
Authors: Mintchev M P , Sanmiguel C P , Otto S J , Bowes K L 
Published: June 2010

Background—Gastric electrical stimulation has been attempted for several years with little success.Aims—To determine whether movement of liquid gastric content could be achieved using microprocessor controlled sequential electrical stimulation.Methods—Eight anaesthetised dogs underwent laparotomy and implantation of four sets of bipolar stainless steel wire electrodes. Each set consisted of two to six electrodes (10×0.25 mm, 3 cm apart) implanted circumferentially. The stomach was filled with water and the process of gastric emptying was monitored. Artificial contractions were produced using microprocessor controlled phase locked bipolar four second trains of 50 Hz, 14 V (peak to peak) rectangular voltage. In four of the dogs four force transducers were implanted close to each circumferential electrode set. In one gastroparetic patient the effect of direct electrical stimulation was determined at laparotomy.Results—Using the above stimulating parameters circumferential gastric contractions were produced which were artificially propagated distally by phase locking the stimulating voltage. Averaged stimulated gastric emptying times were significantly shorter than spontaneus emptying times (t1/2 6.7 (3.0) versus 25.3 (12.9) minutes, p<0.01). Gastric electrical stimulation of the gastroparetic patient at operation produced circumferential contractions.Conclusions—Microprocessor controlled electrical stimulation produced artificial peristalsis and notably accelerated the movement of liquid gastric content.
Phenotypic differences in familial adenomatous polyposis based on APC gene mutation status
Authors: Heinimann K , Müllhaupt B , Weber W , Attenhofer M , Scott R J , Fried M , Martinoli S , Müller Hj , Dobbie Z 
Published: June 2010

Background—Familial adenomatous polyposis (FAP) is a clinically well defined hereditary disease caused by germline mutations within the adenomatous polyposis coli (APC) gene. Although several techniques are applied in the mutation analysis of FAP kindreds about 20–50% of cases remain unclear, with no APC mutation identified (APC negative).Aims—To delineate phenotypic differences between APC positive and APC negative patients with respect to colonic and extracolonic disease in order to determine whether additional mechanisms are involved in the pathogenesis of FAP.Methods—The entire coding region of the APC gene was analysed using single stranded conformation polymorphism and protein truncation tests in 50 Swiss FAP families with a total of 161 affected individuals. Differences in phenotypic manifestation were statistically evaluated by Student’s t test, Fisher’s exact test, and χ2 test.Results—Thirty six families (72%) were APC positive. Statistically significant differences between APC positive and APC negative groups were found for the mean age at diagnosis of colonic polyposis (35.2 versus 45.3 years, respectively) and for the occurrence of stomach polyps (14 patients, all APC positive). Additionally, APC negative patients displayed lower polyp numbers at diagnosis and less extracolonic manifestations.Conclusions—FAP kindreds without detected APC gene mutations present with a notably milder disease phenotype compared with APC positive families, suggesting that different genetic factors might be involved.
Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the cag pathogenicity island
Authors: Jenks P J , Mégraud F , Labigne A 
Published: June 2010

Background—The development of clinical disease after infection with Helicobacter pylori has been reported to be associated with expression of the cagA gene. Recently, it has been shown that cagA is part of a multigene locus, described as the cag pathogenicity island (PAI). The role of this region in determining clinical outcome remains to be established.Aims—To investigate whether the presence ofcagA is always associated with the presence of the complete cag PAI and to evaluate the distribution of selected cag genes in 73 H pylori strains isolated from patients in France.Methods—Clinical strains of H pyloriwere screened for selected genes of the cag PAI by polymerase chain reaction and colony hybridisation.Results—Of 64 strains that harboured thecagA gene, 57 (89%) also contained the entirecag PAI. The entire cag PAI was found in 85% (48/56) and 53% (9/17) of duodenal ulcer and non-ulcer dyspepsia isolates, respectively. Eight strains had deletions within thecag PAI, including deletion of the cagA gene in one isolate; the deletions were not associated with the insertion sequence IS605. Of eight strains lacking the cag PAI, four were isolated from patients with duodenal ulcer.Conclusion—The cag PAI is not a uniform, conserved entity. Although the presence of thecag PAI is highly associated with duodenal ulcer, the clinical outcome of infection with H pylori is not reliably predicted by any gene of the cag PAI.
Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition
Authors: Zoli G , Corazza G R , Wood S , Bartoli R , Gasbarrini G , Farthing M J G 
Published: June 2010

Background—Reticuloendothelial system function is impaired in humans receiving lipid regimens.Aims—To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function.Methods—Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn’s disease who were not receiving intravenous nutrition, and 50 healthy controls.Results—Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p<0.001) than in healthy controls (0.6%) and in patients with Crohn’s disease (0.9%). No difference was found between healthy controls and patients with Crohn’s disease. There was a correlation (r=0.50; p<0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p<0.01) and healthy volunteers (17.8%, p<0.001) . An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition (rs =−0.44, p<0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12 months.Conclusions—Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection.
Scintigraphic validation of a magnetic resonance imaging method to study gastric emptying of a solid meal in humans
Authors: Feinle C , Kunz P , Boesiger P , Fried M , Schwizer W 
Published: June 2010

BackgroundWe have previously used a magnetic resonance imaging (MRI) method to study gastric emptying of liquids. So far, however, it has not possible to assess solid gastric emptying with this technique.AimsTo validate scintigraphically MRI as a method for measuring emptying of a mixed solid/liquid meal.MethodsIn eight healthy subjects, gastric emptying of a solid/liquid (SM) and a liquid meal (LM) of identical energy content and macronutrient composition was studied by scintigraphy and MRI for 120 minutes.ResultsMRI and scintigraphy agreed with respect to emptying profiles (intraclass correlation coefficient (RI) SM: 0.988, RI, LM: 0.917), t1/2 (SMMRI: 129 (9), SMScinti: 123 (11) minutes, NS; LMMRI: 100 (7), LMScinti: 110 (8) minutes, NS) and AUC (SMMRI: 8999 (232), SMScinti: 8788 (277) min%, NS; LMMRI: 8819 (368), LMScinti: 8891 (321) min%, NS).ConclusionsMRI can be used to measure reliably gastric emptying not only of liquid but also of mixed solid/liquid meals in humans.
Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro
Authors: Shimizu I , Mizobuchi Y , Yasuda M , Shiba M , Ma Y-R , Horie T , Liu F , Ito S 
Published: June 2010

BackgroundHepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.AimsTo examine the inhibitory effect of oestradiol on stellate cell activation.MethodsIn vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.ResultsIn the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express α smooth muscle actin (α-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, α-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.ConclusionThe antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis.
Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence?
Authors: Söderholm J D , Olaison G , Lindberg E , Hannestad U , Vindels A , Tysk C , Järnerot G , Sjödahl R 
Published: June 2010

BackgroundA familial defect in intestinal barrier function has been found in Crohn’s disease.AimTo investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn’s disease.SubjectsThe study included 39 patients with Crohn’s disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls.MethodsIntestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the difference between the two tests. A ratio above the 95th percentile for controls was classified as abnormal.ResultsBaseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls.ConclusionThe findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn’s disease.