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1.  Effect of apple cider vinegar on delayed gastric emptying in patients with type 1 diabetes mellitus: a pilot study 
BMC Gastroenterology  2007;7:46.
Background
Previous studies on healthy people show that vinegar delays gastric emptying and lowers postprandial blood glucose and insulin levels. The aim of this study was to investigate the effect of apple cider vinegar on delayed gastric emptying rate on diabetes mellitus patients.
Methods
Ten patients with type 1 diabetes and diabetic gastroparesis, including one patient who had undergone vagotomy, were included and completed the investigator blinded crossover trial. The gastric emptying rate (GER) was measured using standardized real-time ultrasonography. The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of 300 g rice pudding and 200 ml water (GER1), or 300 g rice pudding and 200 ml water with 30 ml apple cider vinegar (GER2). The subjects drank 200 ml water daily before breakfast one week before the measurement of GER1. The same subjects drank 200 ml water with 30 ml vinegar daily before breakfast for two weeks before the measurement of GER2.
Results
The median values of GER1 and GER2 were 27% and 17%, respectively. The effect of vinegar on the rate of gastric emptying was statistically significant (p < 0.05).
Conclusion
This study shows that vinegar affects insulin-dependent diabetes mellitus patients with diabetic gastroparesis by reducing the gastric emptying rate even further, and this might be a disadvantage regarding to their glycaemic control.
Trial registration number
ISRCTN33841495.
doi:10.1186/1471-230X-7-46
PMCID: PMC2245945  PMID: 18093343
2.  Percutaneous ultrasound-guided ablation of BW7756-hepatoma using ethanol or acetic acid in a rat model 
BMC Gastroenterology  2007;7:45.
Background
To compare tumor necrosis in hepatoma induced in rats by a single percutaneous injection of ethanol (PEI) or acetic acid (PAI).
Methods
BW7756 hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14 days, the 36 surviving rats were treated, in a single session, by ultrasound-guided injection of 300 μl of 95% ethanol (n = 17) or 100 μl of 50% acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted tumoral livers were examined. The same PAI procedure was repeated on 13 additional rats to exclude a suspected occurrence of technical failures during the experiment, due to a surprisingly high rate of deaths within 30 minutes after PAI.
Results
Four rats died within four days after tumor implantation; after PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats, after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic examinations showed that the hepatoma's nodules treated with PEI had 45.3 ± 19.4% tumor necrosis compared to 49 ± 23.3% (P = NS) for those treated with PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively (P = NS). Autopsy was performed in the 5 additional rats that died within 30 minutes after PAI.
Conclusion
Our results show that there is no significant difference in the percentage of tumor necrosis between two local ablation methods in spite of the different dosages used. However, mortality in the PAI-treated group was greater than in PEI-treated group, presumably due to greater acetic acid systemic diffusion and its metabolic side effects. In human subjects, HCC occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than the tumor structure, with consequent reduction of drug diffusion. This could be the reason why some human studies have concluded similar or even better safety and efficacy with PAI compared to PEI.
doi:10.1186/1471-230X-7-45
PMCID: PMC2175504  PMID: 18078519
3.  Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study 
BMC Gastroenterology  2007;7:44.
Background
Peroxisome proliferators-activated receptor alpha (PPARα) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis.
Methods
Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1 β), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining.
Results
Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPARα induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01).
Conclusion
Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.
doi:10.1186/1471-230X-7-44
PMCID: PMC2219993  PMID: 18045488
4.  Outcome of index upper gastrointestinal endoscopy in patients presenting with dysphagia in a tertiary care hospital-A 10 years review 
BMC Gastroenterology  2007;7:43.
Background
Patients with malignant tumours of the upper gastrointestinal tract tumours exhibit important alarm symptoms such as dysphagia that warrant clinical investigations. An endoscopic examination of the upper gastrointestinal tract will be required in most cases. This study evaluates the diagnostic potential of index endoscopy in a random population of patients with dysphagia.
Methods
This is a retrospective analysis of prospectively collected data over 10 years. Patients with previous endoscopic evaluation or upper gastrointestinal pathology were excluded from the study. Data was analysed to see the number and frequency of abnormal findings in upper gastrointestinal tract, and their significance in relation to the presenting symptoms.
Results
Total number of index endoscopies was 13, 881. 913 patients were included in the study including 465 males (age range: 17–92 years, median: 55 years) and 448 females (age range: 18–100, median: 59 years), with male to female ratio of 1.04: 1. Oesophagus was abnormal in 678 cases (74%) and biopsies were taken in 428 patients (47%). Superficial oesophagitis, Barrett's oesophagus, oesophageal cancer, and oesophageal ulcer were main histological findings. Age more than 50 years and weight loss were significant predictors of oesophageal cancer (p < 0.0001). Male gender, heartburn, epigastric pain, weight loss and vomiting were significantly related to Barrett's oesophagus. A total of 486 gastric and 56 duodenal biopsies were also taken. There were 20 cases of gastric adenocarcinoma.
Conclusion
OGD is an effective initial investigation to assess patients with dysphagia, especially males above the age of 50 years. Patients may be started on treatment or referred for further investigations, for example, a barium meal in the absence of any anatomical abnormality.
doi:10.1186/1471-230X-7-43
PMCID: PMC2206034  PMID: 18034883
5.  Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design 
BMC Gastroenterology  2007;7:42.
Background
Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.
Methods
We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.
Discussion
Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.
doi:10.1186/1471-230X-7-42
PMCID: PMC2212633  PMID: 18028533
6.  Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units 
BMC Gastroenterology  2007;7:41.
Background
Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy.
Methods/Design
The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography.
A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants.
A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area.
The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score.
Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance.
Discussion
This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors most frequently associated with the presence of this disease to thereby achieve the most appropriate treatment and avoid the evolution of the disease.
doi:10.1186/1471-230X-7-41
PMCID: PMC2151951  PMID: 17983472
7.  Meta-analyses of FibroTest diagnostic value in chronic liver disease 
BMC Gastroenterology  2007;7:40.
Background
FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC).
The aim was to test two hypotheses, one, that the FT diagnostic value was similar in the three other frequent fibrotic diseases: chronic hepatitis B (CHB), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD); and the other, that the FT diagnostic value was similar for intermediate and extreme fibrosis stages.
Methods
The main end points were the FT area under the ROC curves (AUROCs) for the diagnosis of bridging fibrosis (F2F3F4 vs. F0F1), standardized for the spectrum of fibrosis stages, and the comparison of FT AUROCs between adjacent stages. Two meta-analyses were performed: one combining all the published studies (random model), and one of an integrated data base combining individual data. Sensitivity analysis integrated the independency of authors, lenght of biopsy, prospective design, respect of procedures, comorbidities, and duration between biopsy and serum sampling.
Results
A total of 30 studies were included which pooled 6,378 subjects with both FT and biopsy (3,501 HCV, 1,457 HBV, 267 NAFLD, 429 ALD, and 724 mixed). Individual data were analyzed in 3,282 patients. The mean standardized AUROC was 0.84 (95% CI, 0.83–0.86), without differences between causes of liver disease: HCV 0.85 (0.82–0.87), HBV 0.80 (0.77–0.84), NAFLD 0.84 (0.76–0.92), ALD 0.86 (0.80–0.92), mixed 0.85 (0.80–0.93). The AUROC for the diagnosis of the intermediate adjacent stages F2 vs. F1 (0.66; 0.63–0.68, n = 2,055) did not differ from that of the extreme stages F3 vs. F4 (0.69; 0.65–0.72, n = 817) or F1 vs. F0 (0.62; 0.59–0.65, n = 1788).
Conclusion
FibroTest is an effective alternative to biopsy in patients with chronic hepatitis C and B, ALD and NAFLD. The FT diagnostic value is similar for the diagnosis of intermediate and extreme fibrosis stages.
doi:10.1186/1471-230X-7-40
PMCID: PMC2175505  PMID: 17937811
8.  Adherence to colorectal cancer screening guidelines in Canada 
BMC Gastroenterology  2007;7:39.
Background
To identify correlates of adherence to colorectal cancer (CRC) screening guidelines in average-risk Canadians.
Methods
2003 Canadian Community Health Survey Cycle 2.1 respondents who were at least 50 years old, without past or present CRC and living in Ontario, Newfoundland, Saskatchewan, and British Columbia were included. Outcomes, defined according to current CRC screening guidelines, included adherence to: i) fecal occult blood test (FOBT) (in prior 2 years), ii) endoscopy (colonoscopy/sigmoidoscopy) (prior 10 years), and iii) adherence to CRC screening guidelines, defined as either (i) or (ii). Generalized estimating equations regression was employed to identify correlates of the study outcomes.
Results
Of the 17,498 respondents, 70% were non-adherent CRC screening to guidelines. Specifically, 85% and 79% were non-adherent to FOBT and endoscopy, respectively. Correlates for all outcomes were: having a regular physician (OR = (i) 2.68; (ii) 1.91; (iii) 2.39), getting a flu shot (OR = (i) 1.59; (ii) 1.51; (iii) 1.55), and having a chronic condition (OR = (i) 1.32; (ii) 1.48; (iii) 1.43). Greater physical activity, higher consumption of fruits and vegetables and smoking cessation were each associated with at least 1 outcome. Self-perceived stress was modestly associated with increased odds of adherence to endoscopy and to CRC screening guidelines (OR = (ii) 1.07; (iii) 1.06, respectively).
Conclusion
Healthy lifestyle behaviors and factors that motivate people to seek health care were associated with adherence, implying that invitations for CRC screening should come from sources that are independent of physicians, such as the government, in order to reduce disparities in CRC screening.
doi:10.1186/1471-230X-7-39
PMCID: PMC2194682  PMID: 17910769
9.  "It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease 
BMC Gastroenterology  2007;7:38.
Background
Interest in psychological factors in patients with inflammatory bowel disease (IBD) has increased in recent years. It has even been proposed that treating psychological co-morbidities with antidepressants may control disease activity and improve quality of life. Despite this, there is no data on gastroenterologists' attitudes to, and experiences with, antidepressant therapy in patients with IBD.
Methods
We conducted semi-structured interviews with 18 gastroenterologists associated with metropolitan teaching hospitals. Qualitative content analysis was used to examine their responses.
Results
Seventy-eight percent of gastroenterologists had treated IBD patients with antidepressants for pain, depression and/or anxiety, and insomnia. Antidepressants were reported to be useful in improving psychosocial well-being, quality of life, and self-management of the disease by patients. However, in this group of gastroenterologists, there appears to be skepticism towards psychological disorders themselves or antidepressant therapy having a central role in either the causation of IBD or its clinical course. Nevertheless, these gastroenterologists were receptive to the idea of conducting a trial of the role of antidepressants in IBD.
Conclusion
While the majority of specialists have treated IBD patients with antidepressants, there is considerable skepticism with regard to efficacy of antidepressive therapy or the role of psychological factors in the outcome of IBD patients.
doi:10.1186/1471-230X-7-38
PMCID: PMC2040148  PMID: 17892587
10.  Colonic epithelial ion transport is not affected in patients with diverticulosis 
BMC Gastroenterology  2007;7:37.
Background
Colonic diverticular disease is a bothersome condition with an unresolved pathogenesis. It is unknown whether a neuroepithelial dysfunction is present. The aim of the study was two-fold; (1) to investigate colonic epithelial ion transport in patients with diverticulosis and (2) to adapt a miniaturized Modified Ussing Air-Suction (MUAS) chamber for colonic endoscopic biopsies.
Methods
Biopsies were obtained from the sigmoid part of the colon. 86 patients were included. All patients were referred for colonoscopy on suspicion of neoplasia and they were without pathological findings at colonoscopy (controls) except for diverticulosis in 22 (D-patients). Biopsies were mounted in MUAS chambers with an exposed area of 5 mm2. Electrical responses to various stimulators and inhibitors of ion transport were investigated together with histological examination. The MUAS chamber was easy to use and reproducible data were obtained.
Results
Median basal short circuit current (SCC) was 43.8 μA·cm-2 (0.8 – 199) for controls and 59.3 μA·cm-2 (3.0 – 177.2) for D-patients. Slope conductance was 77.0 mS·cm-2 (18.6 – 204.0) equal to 13 Ω·cm2 for controls and 96.6 mS·cm-2 (8.4 – 191.4) equal to 10.3 Ω·cm2 for D-patients. Stimulation with serotonin, theophylline, forskolin and carbachol induced increases in SCC in a range of 4.9 – 18.6 μA·cm-2, while inhibition with indomethacin, bumetanide, ouabain and amiloride decreased SCC in a range of 6.5 – 27.4 μA·cm-2, and all with no significant differences between controls and D-patients. Histological examinations showed intact epithelium and lamina propria before and after mounting for both types of patients.
Conclusion
We conclude that epithelial ion transport is not significantly altered in patients with diverticulosis and that the MUAS chamber can be adapted for studies of human colonic endoscopic biopsies.
doi:10.1186/1471-230X-7-37
PMCID: PMC2064914  PMID: 17888183
11.  Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study 
BMC Gastroenterology  2007;7:36.
Background
The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.
Methods
Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.
Results
14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).
Conclusion
The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.
Trial registration
Current Controlled Trials ISRCTN92101486
doi:10.1186/1471-230X-7-36
PMCID: PMC1995200  PMID: 17784949
12.  Cholecystectomy in Sweden 2000 – 2003: a nationwide study on procedures, patient characteristics, and mortality 
BMC Gastroenterology  2007;7:35.
Background
Epidemiological data on characteristics of patients undergoing open or laparoscopic cholecystectomy are limited. In this register study we examined characteristics and mortality of patients who underwent cholecystectomy during hospital stay in Sweden 2000 – 2003.
Methods
Hospital discharge and death certificate data were linked for all patients undergoing cholecystectomy in Sweden from January 1st 2000 through December 31st 2003. Mortality risk was calculated as standardised mortality ratio (SMR) i.e. observed over expected deaths considering age and gender of the background population.
Results
During the four years of the study 43072 patients underwent cholecystectomy for benign biliary disease, 31144 (72%) using a laparoscopic technique and 11928 patients (28%) an open procedure (including conversion from laparoscopy). Patients with open cholecystectomy were older than patients with laparoscopic cholecystectomy (59 vs 49 years, p < 0.001), they were more likely to have been admitted to hospital during the year preceding cholecystectomy, and they had more frequently been admitted acutely for cholecystectomy (57% Vs 21%, p < 0.001). The proportion of women was lower in the open cholecystectomy group compared to the laparoscopic group (57% vs 73%, p < 0.001). Hospital stay was 7.9 (8.9) days, mean (SD), for patients with open cholecystectomy and 2.6 (3.3) days for patients with laparoscopic cholecystectomy, p < 0.001. SMR within 90 days of index admission was 3.89 (3.41–4.41) (mean and 95% CI), for patients with open cholecystectomy and 0.73 (0.52–1.01) for patients with laparoscopic cholecystectomy. During this period biliary disease accounted for one third of all deaths in both groups. From 91 to 365 days after index admission, SMR for patients in the open group was 1.01 (0.87–1.16) and for patients in the laparoscopic group 0.56 (0.44–0.69).
Conclusion
Laparoscopic cholecystectomy is performed on patients having a lower mortality risk than the general Swedish population. Patients with open cholecystectomy are more sick than patients with laparoscopic cholecystectomy, and they have a mortality risk within 90 days of admission for cholecystectomy, which is four times that of the general population. Further efforts to reduce surgical trauma in open biliary surgery are motivated.
doi:10.1186/1471-230X-7-35
PMCID: PMC2040147  PMID: 17705871
13.  Portal vein thrombosis; risk factors, clinical presentation and treatment 
BMC Gastroenterology  2007;7:34.
Background
Portal vein thrombosis (PVT) is increasingly frequently being diagnosed, but systematic descriptions of the natural history and clinical handling of the condition are sparse. The aim of this retrospective study was to describe risk factors, clinical presentation, complications and treatment of portal vein thrombosis in a single-centre.
Methods
Sixty-seven patients were identified in the electronic records from 1992 to 2005. All data were obtained from the patient records.
Results
One or more risk factors (e.g. prothrombotic disorder or abdominal inflammation) were present in 87%. Symptoms were abdominalia, splenomegaly, fever, ascites, haematemesis, and weight loss. Abdominalia and fever occurred more frequently in patients with acute PVT. Frequent complications were splenomegaly, oesophageal- and gastric varices with or without bleeding, portal hypertensive gastropathy and ascites. Varices and bleeding were more frequent in patients with chronic PVT. Patients who received anticoagulant therapy more frequently achieved partial/complete recanalization. Patients with varices who were treated endoscopically in combination with β-blockade had regression of the varices. The overall mortality was 13% in one year, and was dependent on underlying causes.
Conclusion
Most patients had a combination of local and systemic risk factors for PVT. We observed that partial/complete recanalization was more frequent in patients treated with anticoagulation therapy, and that regression of varices was more pronounced in patients who where treated with active endoscopy combined with pharmacological treatment.
doi:10.1186/1471-230X-7-34
PMCID: PMC1976099  PMID: 17697371
14.  Subclinical sympathetic neuropathy appears early in the course of Crohn's disease 
BMC Gastroenterology  2007;7:33.
Background
We have previously demonstrated that patients with Crohn's disease (CD) of long duration have signs of autonomic neuropathy. The aim of this study was to examine whether autonomic neuropathy is an early manifestation of CD, or a sign appearing late in the course.
Methods
Twenty patients, median age 40 years, with a short duration of CD were included. Examination of autonomic reflexes included heart rate reaction to tilt (acceleration index – AI, brake index – BI) and heart rate variation to deep-breathing (expiration/inspiration index-E/I). Seven years later the same examinations were repeated, and in addition we examined the vasoconstriction response to indirect cooling by laser Doppler (vasoconstriction-index – VAC-index). The results were compared with healthy individuals.
Results
There was no difference in the blood pressure between controls and the patients with CD at rest, but eight minutes after tilt, the systolic blood pressure was lowered in patients compared to controls, both at the first assessment (p = 0.016) and after seven years (p = 0.042). The change in systolic blood pressure between rest and eight minutes after tilt was not significant at the first assessment, while a significant change compared to controls was observed seven years later (p = 0.028). This indicates a progressive dysfunction. There were no differences in E/I, AI, BI or VAC indexes between patients and controls.
Conclusion
Patients with CD suffer from autonomic neuropathy early in their disease, suggesting involvement of many different organ systems in this entity.
doi:10.1186/1471-230X-7-33
PMCID: PMC1978494  PMID: 17697346
15.  Grey scale enhancement by a new self-made contrast agent in early cirrhotic stage of rabbit liver 
BMC Gastroenterology  2007;7:32.
Background
The development of new ultrasound contrast agents (UCAs) has become one of the most promising fields in ultrasound medicine. This paper evaluates a new self-made contrast agent enhancement effect developed to study the fibrotic stages of the liver in perfusion models in vivo.
Methods
We constructed experimental models of hepatic fibrosis involving five stages from F0 to F4 via administration of CCL4 (0.01 ml/kg BW) every 3 days for 3 months. The intrahepatic circulatory time of the contrast agent was analyzed via an image and Cine-loop display. Calculations of the perfusion-related parameters including the peak signal intensity (PSI) and peak signal intensity time (PIT) of the portal vein and parenchyma were obtained from an analysis of the time-acoustic intensity curve.
Results
Hepatic artery to vein transmit time (HA-HVTT) was significantly shorter at F4 stage (mean 5.1 seconds) compared with those in other stages (mean 8.3 s, 7.5 s, 6.9 s, 6.6 s, P < 0.01). The average PSI difference of PV-parenchyma was 13.62 dB in F4 stage, demonstrating significant differences between F4 stage and other early stages (P < 0.001).
Conclusion
These results indicate that the new self-made contrast agent is capable of indicating intrahepatic hemodynamic changes. HA-HVTT and the PSI difference of the microbubble perfusion in liver parenchyma and PV were considered to differentiate the degree of hepatic fibrosis between F4 and other early stages.
doi:10.1186/1471-230X-7-32
PMCID: PMC1963445  PMID: 17686161
16.  Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection 
BMC Gastroenterology  2007;7:31.
Background
Rifabutin has been found to be effective in multi-resistant patients after various treatment cycles for Helicobacter pylori (HP) infection, but it has not been analysed as a second-line treatment. Therefore, we seek to compare the effectiveness of a treatment regimen including rifabutin versus conventional quadruple therapy (QT).
Methods
Open clinical trial, randomised and multi-centre, of two treatment protocols: A) Conventional regime -QT- (omeprazole 20 mg bid, bismuth citrate 120 mg qid, tetracycline 500 mg qid and metronidazole 500 mg tid); B) Experimental one -OAR- (omeprazole 20 mg bid, amoxicillin 1 gr bid, and rifabutin 150 mg bid), both taken orally for 7 days, in patients with HP infection for whom first-line treatment had failed. Eradication was determined by Urea Breath Test (UBT). Safety was determined by the adverse events.
Results
99 patients were randomised, QT, n = 54; OAR, n = 45. The two groups were homogeneous. In 8 cases, treatment was suspended (6 in QT and 2 in OAR). The eradication achieved, analysed by ITT, was for QT, 38 cases (70.4%), and for OAR, 20 cases (44.4%); p = 0.009, OR = 1.58. Of the cases analysed PP, QT were 77.1%; OAR, 46.5%; p = 0.002. Adverse effects were described in 64% of the QT patients and in 44% of the OAR patients (p = 0.04).
Conclusion
A 7-day rifabutin-based triple therapy associated to amoxicillin and omeprazole at standard dose was not found to be effective as a second-line rescue therapy. The problem with quadruple therapy lies in the adverse side effects it provokes. We believe the search should continue for alternatives that are more comfortably administered and that are at least as effective, but with fewer adverse side effects.
Trial Registration
Current Controlled Trials ISRCTN81058036
doi:10.1186/1471-230X-7-31
PMCID: PMC1941741  PMID: 17651479
17.  Endoscopists attitudes on the publication of "quality" data for endoscopic procedures: a cross-sectional survey 
BMC Gastroenterology  2007;7:30.
Background
Whilst the public now have access to mortality & morbidity data for cardiothoracic surgeons, such "quality" data for endoscopy are not generally available. We studied endoscopists' attitudes to and the practicality of this data being published.
Methods
We sent a questionnaire to all consultant gastrointestinal (GI) surgeons, physicians and medical GI specialist registrars in the Northern region who currently perform GI endoscopic procedures (n = 132). We recorded endoscopist demographics, experience and current data collection practice. We also assessed the acceptability and utility of nine items describing endoscopic "quality" (e.g. mortality, complication & completion rates).
Results
103 (78%) doctors responded of whom 79 were consultants (77%). 61 (59%) respondents were physicians. 77 (75%) collect any "quality" data. The most frequently collected item was colonoscopic completion rate. Data were most commonly collected for appraisal, audit or clinical governance. The majority of doctors (54%) kept these data only available to themselves, and just one allowed the public to access this. The most acceptable data item was annual number of endoscopies and the least was crude upper GI bleeding mortality. Surgeons rated information less acceptable and less useful than physicians. Acceptability and utility scores were not related to gender, length of experience or current activity levels. Only two respondents thought all items totally unacceptable and useless.
Conclusion
The majority of endoscopists currently collect "quality" data for their practice although these are not widely available. The endoscopists in this study consider the publication of their outcome data to be "fairly unacceptable/not very useful" to "neutral" (score 2–3). If these data were made available to patients, consideration must be given to both its value and its acceptability.
doi:10.1186/1471-230X-7-30
PMCID: PMC1950092  PMID: 17650317
18.  Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy 
BMC Gastroenterology  2007;7:29.
Background
Capsule endoscopy (CE) is a unique tool to visualize the mucosa of the small intestine. Chronic intestinal dysmotility (CID) is a group of rare disorders of gastrointestinal motility that often are complicated by bacterial overgrowth. The aim of this study was to determine the prevalence of small bowel mucosal abnormalities in patients with CID. We also studied the usefulness of CE in the diagnosis of intestinal dysmotility.
Methods
We conducted a prospective study using CE in 18 patients; six with myopathic, 11 with neuropathic and one with indeterminate CID. A control group was used for comparison of small bowel transit.
Results
Mucosal breaks (erosions and ulcerations) were found in 16/18 (89%) patients. The capsule reached the caecum in 11/18 (61%) patients with a median transit time of 346 minutes. In the control group the capsule reached the caecum in 29/36 (81%) cases with a median transit time of 241 minutes. The difference in transit time was not significant (p = 0.061) in this material. The capsule was retained in the stomach in 3/18 patients. None of the patients developed symptoms or signs of mechanical obstruction.
Conclusion
A high frequency of mucosal breaks and signs of motility disturbances were seen in CID patients. CE is feasible for the examination of small bowel mucosa in patients with CID. The relevance of observed mucosal abnormalities in CID remains uncertain.
doi:10.1186/1471-230X-7-29
PMCID: PMC1940016  PMID: 17640373
19.  Anxiety and depression in patients with gastrointestinal cancer: does knowledge of cancer diagnosis matter? 
BMC Gastroenterology  2007;7:28.
Background
Gastrointestinal cancer is the first leading cause of cancer related deaths in men and the second among women in Iran. An investigation was carried out to examine anxiety and depression in this group of patients and to investigate whether the knowledge of cancer diagnosis affect their psychological distress.
Methods
This was a cross sectional study of anxiety and depression in patients with gastrointestinal cancer attending to the Tehran Cancer Institute. Anxiety and depression was measured using the Hospital Anxiety and Depression Scale (HADS). This is a widely used valid questionnaire to measure psychological distress in cancer patients. Demographic and clinical data also were collected to examine anxiety and depression in sub-group of patients especially in those who knew their cancer diagnosis and those who did not.
Results
In all 142 patients were studied. The mean age of patients was 54.1 (SD = 14.8), 56% were male, 52% did not know their cancer diagnosis, and their diagnosis was related to esophagus (29%), stomach (30%), small intestine (3%), colon (22%) and rectum (16%). The mean anxiety score was 7.6 (SD = 4.5) and for the depression this was 8.4 (SD = 3.8). Overall 47.2% and 57% of patients scored high on both anxiety and depression. There were no significant differences between gender, educational level, marital status, cancer site and anxiety and depression scores whereas those who knew their diagnosis showed a significant higher degree of psychological distress [mean (SD) anxiety score: knew diagnosis 9.1 (4.2) vs. 6.3 (4.4) did not know diagnosis, P < 0.001; mean (SD) depression score: knew diagnosis 9.1 (4.1) vs. 7.9 (3.6) did not know diagnosis, P = 0.05]. Performing logistic regression analysis while controlling for demographic and clinical variables studied the results indicated that those who knew their cancer diagnosis showed a significant higher risk of anxiety [OR: 2.7, 95% CI: 1.1–6.8] and depression [OR: 2.8, 95% CI: 1.1–7.2].
Conclusion
Psychological distress was higher in those who knew their cancer diagnosis. It seems that the cultural issues and the way we provide information for cancer patients play important role in their improved or decreased psychological well-being.
doi:10.1186/1471-230X-7-28
PMCID: PMC1971049  PMID: 17629928
20.  Effects of abdominal hot compresses on indocyanine green elimination – a randomized cross over study in healthy subjects 
BMC Gastroenterology  2007;7:27.
Background
Hot compresses on the right upper abdomen are used as support for patients with liver diseases in Germany. The study was designed to determine, whether they affect hepatic blood flow.
Methods
Single dose kinetics of indocyanine green (ICG) were studied in 13 healthy subjects with or without hot compresses on the right upper abdomen over 40 minutes. The time interval between the investigations was 8 days, the sequence was randomly assigned.
Results
Within non-linear kinetic analyses the area under the curves (AUC) were 23% (95% confidence interval [CI]: 5–37%) lower with hot compresses. In the initial phase, however, no differences were detected (p = 0.295). The differences occurred only in the late phase after 30–40 minutes, when the genuine ICG is eliminated from the plasma and only the degradation product remains.
Conclusion
Hot compresses have no effect on ICG elimination in healthy subjects but seem to affect the elimination of ICG metabolites.
Trial registration
ClinicalTrials.gov NCT00484913
doi:10.1186/1471-230X-7-27
PMCID: PMC1931598  PMID: 17623067
21.  Anomalous opening of the common bile duct into the duodenal bulb: endoscopic treatment 
BMC Gastroenterology  2007;7:26.
Background
Anomalous biliary opening especially the presence of the ampulla of Vater in the duodenal bulb is a very rare phenomenon. We report clinical implications, laboratory and ERCP findings and also therapeutic approaches in 53 cases.
Methods
The data were collected from the records of 12.158 ERCP. The diagnosis was established as an anomalous opening of the common bile duct (CBD) into the duodenal bulb when there is an orifice observed in the bulb with the absence of a papillary structure at its normal localization and when the CBD is visualized by cholangiography through this orifice without evidence of any other opening.
Results
A total of 53 cases were recruited. There was an obvious male preponderance (M/F: 49/4). Demographic data and ERCP findings were available for all, but clinical characteristics and laboratory findings could be obtained from 39 patients with full records. Thirty – seven of 39 cases had abdominal pain (95%) and 23 of them (59%) had cholangitis as well. Elevated AP and GGT were found in 97.4% (52/53). History of cholecystectomy was present in 64% of the cases, recurrent cholangitis in 26% and duodenal ulcer in 45%. Normal papilla was not observed in any of the patients and a cleft-like opening was evident instead. The CBD was hook shaped at the distal part that opens to the duodenal bulb. Pancreatic duct (PD) was opening separately into the bulb in all the cases when it was possible to visualize. Dilated CBD in ERCP was evident in 94% and the CBD stone was demonstrated in 51%. PD was dilated in four of 12 (33%) cases. None of them has a history of pancreatitis. Endoscopically, Papillary Balloon Dilatation instead of Sphincterotomy carried out in 19 of 27 patients (70%) with choledocholithiazis. Remaining eight patients had undergone surgery (30%). Clinical symptoms were resolved with medical treatment in 16(32%) patients with dilated CBD but no stone. Perforation and bleeding were occurred only in two patients, which stones extracted with sphincterotomy (each complication in 1 patient).
Conclusion
The opening of the CBD into the duodenal bulb is a rare event that may be associated with biliary and gastric/duodenal diseases. To date, surgical treatment has been preferred. In our experience, sphincterotomy has a high risk since it may lead to bleeding and perforation by virtue of the fact that a true papillary structure is absent. However, we performed balloon dilatation of the orifice successfully without any serious complication and suggest this as a safe therapeutic modality.
doi:10.1186/1471-230X-7-26
PMCID: PMC1933541  PMID: 17610747
22.  An economic model of long-term use of celecoxib in patients with osteoarthritis 
BMC Gastroenterology  2007;7:25.
Background
Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.
Methods
We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.
Results
Our main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.
Conclusion
Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.
doi:10.1186/1471-230X-7-25
PMCID: PMC1925103  PMID: 17610716
23.  Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure 
BMC Gastroenterology  2007;7:24.
Background
Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.
Methods
Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.
Results
The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.
Conclusion
Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.
doi:10.1186/1471-230X-7-24
PMCID: PMC1925102  PMID: 17597535
24.  Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study 
BMC Gastroenterology  2007;7:23.
Background
It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also.
Methods
By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit© L30D-55.
Results
Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022–0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035–0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033–0.065)) nor adenosine (0.050 (0.030–0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant.
Conclusion
In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.
doi:10.1186/1471-230X-7-23
PMCID: PMC1913056  PMID: 17578566
25.  Septic thrombophlebitis of the superior mesenteric vein and multiple liver abscesses in a patient with Crohn's disease at onset 
BMC Gastroenterology  2007;7:22.
Background
Portal-mesenteric vein thrombosis, pylephlebitis and liver abscesses are rare complications of inflammatory bowel disease (IBD). The purpose of this case report is to relate an unusual presentation of CD in order to show how conservative treatment could be an appropriate option as a bridge to the surgery, in patients with septic thrombophlebitis and multiple liver abscesses with CD.
Case presentation
We report a case of a 25-year-old man with Crohn's disease (CD) who developed a superior mesenteric venous thrombosis, multiple liver abscesses and pylephlebitis, diagnosed through abdominal ultrasound and an abdominal computed tomography (CT) scan. The patient was successfully treated with conservative treatment consisting of intravenous antibiotics, subcutaneous anticoagulation and percutaneous catheter drainage of liver abscesses.
Conclusion
We reported an unnusual case of pylephlebitis in CD. Until now this association has not been reported in adult patients at onset. We hypothesise that the infection developed as a result of mucosal disease and predisposed by corticoid therapy. Adequated management was discussed.
doi:10.1186/1471-230X-7-22
PMCID: PMC1904453  PMID: 17565671

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