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1.  Outcomes in culture positive and culture negative ascitic fluid infection in patients with viral cirrhosis: cohort study 
BMC Gastroenterology  2008;8:59.
Background
Ascitic fluid infection (AFI) in cirrhotic patients has a high morbidity and mortality. It has two variants namely, spontaneous bacterial peritonitis (SBP) and culture negative neutrocytic ascites (CNNA). The aim of this study was to determine the outcome in cirrhotic patients with culture positive (SBP) and culture negative neutrocytic ascites.
Methods
We analyzed 675 consecutive hepatitis B and/or C related cirrhosis patients with ascites admitted in our hospital from November 2005 to December 2007. Of these, 187 patients had AFI; clinical and laboratory parameters of these patients including causes of cirrhosis, Child Turcotte Pugh (CTP) score were recorded.
Results
Out of 187 patients with AFI, 44 (23.5%) had SBP while 143 (76.4%) had CNNA. Hepatitis C virus (HCV) infection was the most common cause of cirrhosis in 139 (74.3%) patients. Patients with SBP had high CTP score as compared to CNNA (12.52 ± 1.45 vs. 11.44 ± 1.66); p < 0.001. Platelets count was low in patients with SBP (101 ± 53 × 109/L) as compared to CNNA (132 ± 91 × 109/L), p = 0.005. We found a high creatinine (mg/dl) (1.95 ± 1.0 vs. 1.44 ± 0.85), (p = 0.003) and high prothrombin time (PT) in seconds (24.8 ± 6.6 vs. 22.4 ± 7.2) (p = 0.04) in SBP as compared to CNNA. More patients with SBP (14/44; 31.8%) had blood culture positivity as compare to CNNA (14/143; 9.8%), p = 0.002. Escherichia. Coli was the commonest organism in blood culture in 15/28 (53.5%) patients. SBP group had a higher mortality (11/44; 25%) as compared to CNNA (12/143; 8.4%), p = 0.003. On multiple logistic regression analysis, creatinine >1.1 mg/dl and positive blood culture were the independent predictors of mortality in patients with SBP.
Conclusion
Patients with SBP have a higher mortality than CNNA. Independent predictors of mortality in SBP are raised serum creatinine and a positive blood culture.
doi:10.1186/1471-230X-8-59
PMCID: PMC2628346  PMID: 19091136
2.  Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men 
BMC Gastroenterology  2008;8:58.
Background
Evidence regarding the association between alcohol consumption and the gastro-esophageal reflux disease (GERD) spectrum has been conflicting. We examined the association between alcohol consumption and erosive esophagitis and Barrett's epithelium in Japanese men.
Methods
The study population comprised 463 men subjects who had undergone an upper endoscopy at the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. The presence of erosive esophagitis and Barrett's epithelium was diagnosed based on the Los Angeles Classification and the Prague C and M Criteria, respectively. We divided the study population into four groups: never drinkers, light drinkers (less than 25.0 g of ethanol per day), moderate drinkers (25.0 to 50.0 g of ethanol per day), and heavy drinkers (more than 50.0 g of ethanol per day). A linear regression of the logistic regression analysis was used to analyze the dose-response trends.
Results
Compared with never drinkers, light drinkers (less than 25.0 g ethanol per day), moderate drinkers (25.0 to 50.0 g per day), and heavy drinkers (more than 50.0 g per day) had ORs for erosive esophagitis of 1.110 (95% CI: 0.553 – 2.228, p = 0.7688), 1.880 (95% CI: 1.015 – 3.484, p = 0.0445) and 1.988 (95% CI: 1.120 – 3.534, p = 0.0190), respectively. These groups had ORs for Barrett's epithelium of 1.278 (95% CI: 0.752 – 2.170, p = 0.3643), 1.458 (95% CI: 0.873 – 2.433, p = 0.1500), and 1.912 (95% CI: 1.185 – 3.086, p = 0.0079), respectively. The odds ratios/grams (alcohol)/day of dose response trends for erosive esophagitis and Barrett's epithelium were 1.015 (95% CI: 1.004–1.026, p = 0.0066) and 1.012 (95% CI: 1.003–1.021, p = 0.0079), respectively.
Conclusion
These findings suggest that alcohol consumption in Japanese men tends to be associated with an increased risk of erosive esophagitis and Barrett's epithelium.
doi:10.1186/1471-230X-8-58
PMCID: PMC2615024  PMID: 19077221
3.  Wnt-reporter expression pattern in the mouse intestine during homeostasis 
BMC Gastroenterology  2008;8:57.
Background
The canonical Wnt signaling pathway is a known regulator of cell proliferation during development and maintenance of the intestinal epithelium. Perturbations in this pathway lead to aberrant epithelial proliferation and intestinal cancer. In the mature intestine, proliferation is confined to the relatively quiescent stem cells and the rapidly cycling transient-amplifying cells in the intestinal crypts. Although the Wnt signal is believed to regulate all proliferating intestinal cells, surprisingly, this has not been thoroughly demonstrated. This important determination has implications on intestinal function, especially during epithelial expansion and regeneration, and warrants an extensive characterization of Wnt-activated cells.
Methods
To identify intestinal epithelial cells that actively receive a Wnt signal, we analyzed intestinal Wnt-reporter expression patterns in two different mouse lines using immunohistochemistry, enzymatic activity, in situ hybridization and qRT-PCR, then corroborated results with reporter-independent analyses. Wnt-receiving cells were further characterized for co-expression of proliferation markers, putative stem cell markers and cellular differentiation markers using an immunohistochemical approach. Finally, to demonstrate that Wnt-reporter mice have utility in detecting perturbations in intestinal Wnt signaling, the reporter response to gamma-irradiation was examined.
Results
Wnt-activated cells were primarily restricted to the base of the small intestinal and colonic crypts, and were highest in numbers in the proximal small intestine, decreasing in frequency in a gradient toward the large intestine. Interestingly, the majority of the Wnt-reporter-expressing cells did not overlap with the transient-amplifying cell population. Further, while Wnt-activated cells expressed the putative stem cell marker Musashi-1, they did not co-express DCAMKL-1 or cell differentiation markers. Finally, gamma-irradiation stimulated an increase in Wnt-activated intestinal crypt cells.
Conclusion
We show, for the first time, detailed characterization of the intestine from Wnt-reporter mice. Further, our data show that the majority of Wnt-receiving cells reside in the stem cell niche of the crypt base and do not extend into the proliferative transient-amplifying cell population. We also show that the Wnt-reporter mice can be used to detect changes in intestinal epithelial Wnt signaling upon physiologic injury. Our findings have an important impact on understanding the regulation of the intestinal stem cell hierarchy during homeostasis and in disease states.
doi:10.1186/1471-230X-8-57
PMCID: PMC2615026  PMID: 19055726
4.  Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels, in patients with inflammatory bowel disease 
BMC Gastroenterology  2008;8:55.
Background
Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).
Methods
TIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohn's disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded.
Results
Mean serum TIMP-1 levels were 414.9 ± 17.6 ng/mL in UC patients, 446.1 ± 22.8 ng/mL in CD patients and 296.5 ± 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p < 0.0001 in both groups). Mean serum TIMP-1 levels were significantly higher in patients with active IBD (450.5 ng/mL) in comparison with patients with inactive disease (417.3 ng/mL, p = 0.03). Moreover, males showed significantly higher mean serum TIMP-1 levels (399.8 ng/mL), compared to females (368.5 ng/mL, p = 0.04). Mean serum TIMP-2 levels did not differ between UC and CD patients or HC (p > 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 ± 67.7 pg/mL in UC patients, 1708.1 ± 73.4 pg/mL in CD patients and 5573.4 ± 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03).
Conclusion
An imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter.
doi:10.1186/1471-230X-8-55
PMCID: PMC2613880  PMID: 19036126
5.  Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival 
BMC Gastroenterology  2008;8:56.
Background
The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases.
Methods
Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls.
Results
PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012).
Conclusion
Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.
doi:10.1186/1471-230X-8-56
PMCID: PMC2611992  PMID: 19036165
6.  Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis (NASH) 
BMC Gastroenterology  2008;8:53.
Background
The changes in the liver in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However it has remained difficult to differentiate between NASH and non-progressive NAFLD on the basis of the clinical findings alone.
Aims
In this study we investigated the clinical usefulness of plasma Pentraxin3 (PTX3) levels to predict NASH. Plasma PTX3 was measured in 70 patients with histologically verified NAFLD (28 with non-NASH and 42 with NASH) and 10 healthy control subjects.
Results
The plasma PTX3 level was significantly higher in the NASH cases than in the non-NASH cases (p = 0.0021) and control subjects (p = 0.045). And the plasma PTX3 level was significantly higher in the stages 3–4 NAFLD cases than in the stages 0–2 NAFLD cases (p < 0.0001). The PTX3 values were closely correlated with the stages of liver fibrosis (p < 0.0001, Kruskal-Wallis test). To detect NASH compared with non-NASH, the area under the curve for plasma PTX3 were 0.755, and to detect stages 3–4 NAFLD compared with stages 0–2 NAFLD, the area under the curve for plasma PTX3 were 0.850.
Conclusion
This is the first study to demonstrate consistent and profound elevation of plasma PTX3 levels in NASH in comparison with non-NASH. The results suggest that plasma PTX3 levels may not only be laboratory values that differentiate NASH from non-NASH, but marker of the severity of hepatic fibrosis in NASH.
doi:10.1186/1471-230X-8-53
PMCID: PMC2621235  PMID: 19014569
7.  Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study 
BMC Gastroenterology  2008;8:54.
Background
Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation.
Methods
Crypt length, crypt cellularity and crypt cell proliferation were assessed in biopsies acquired after preparation with either Klean-Prep or Picolax. Crypt cell proliferation was assessed by whole-mount mitotic figure count, and by two different immunohistochemical (IHC) labelling methods (Ki-67 and pHH3). Subsequent biopsies were obtained from the same patients without bowel preparation and similarly assessed. Parameters were compared between groups using analysis of variance and paired t-tests.
Results
There were significant differences in labelling indices (LI) between biopsies taken after Klean-prep and those taken after Picolax preparation, for both Ki67 (p = 0.019) and pHH3 (p = 0.017). A similar trend was seen for whole-mount mitotic figure counts. Suppression or elevation of proliferation parameters by bowel preparation may mask any effect due to an intervention or disease.
Conclusion
Commonly used bowel preparations may have significant and different effects on crypt cell proliferation. This should be taken into account when designing studies and when considering the findings of existing studies.
doi:10.1186/1471-230X-8-54
PMCID: PMC2588612  PMID: 19014572
8.  Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms 
BMC Gastroenterology  2008;8:52.
Background
Iron deficiency anaemia (IDA) due to occult gastrointestinal (GI) blood loss usually remains unnoticed until patient become symptomatic. There is sparse data in IDA patients without gastrointestinal symptoms. This study was designed to find out the frequency and predictors of endoscopic lesions in IDA without gastrointestinal symptoms. Cross-sectional study performed on a convenience sample of consecutive subjects.
Methods
Ninety five consecutive patients with laboratory based diagnosis of IDA having no gastrointestinal symptoms were interviewed and their clinical and biochemical variables were recorded. All the study patients underwent esophago-gastroduodenoscopy (EGD) and colonoscopy. Endoscopic findings were documented as presence/absence of bleeding related lesion and presence/absence of cause of IDA. Multiple logistic regressions were performed to identify variables significantly related to outcome variables.
Results
Possible cause of anaemia was found in 71% and bleeding related lesions were found in 53% of patients. Upper gastrointestinal tract lesions were found in 41% of patients with bleeding related lesions. On multivariable logistic regression; advancing age, low mean corpuscular volume (MCV ≤ 60 fl), and positive fecal occult blood test were predictive factors for bleeding related GI lesions and cause of IDA
Conclusion
Clinical and Biochemical markers can predict gastrointestinal lesions on endoscopy in IDA patients without gastrointestinal symptoms. High proportion of upper gastrointestinal involvement warrants EGD as initial endoscopic procedure however, this needs validation by further studies.
doi:10.1186/1471-230X-8-52
PMCID: PMC2613391  PMID: 18992171
9.  Scintigraphic evaluation of oesophageal transit during radiotherapy to the mediastinum 
BMC Gastroenterology  2008;8:51.
Background
To quantitatively evaluate radiation-induced impaired oesophageal transit with oesophageal transit scintigraphy and to assess the relationships between acute oesophagitis symptoms and dysmotility.
Methods
Between January 1996 and November 1998, 11 patients affected by non-small-cell carcinoma of the lung not directly involving the oesophagus, requiring adjuvant external beam radiotherapy (RT) to the mediastinum were enrolled. Oesophageal transit scans with liquid and semisolid bolus were performed at three pre-defined times: before (T0) and during radiation at 10 Gy (T1) and 30 Gy (T2). Two parameters were obtained for evaluation: 1) mean transit time (MTT); and 2) ratio between peak activity and residual activity at 40 seconds (ER-40s). Acute radiation toxicity was scored according to the joint EORTC-RTOG criteria. Mean values with standard deviation were calculated for all parameters. Analysis of variance (ANOVA) tests and paired t-Tests for all values were performed.
Results
An increase in the ER-40s from T0 to T1 or T2 was seen in 9 of 11 patients (82%). The mean ER-40s value for all patients increased from 0.8306 (T0) to 0.8612 (T1) and 0.8658 (T2). These differences were statistically significant (p < 0.05) in two paired t-Tests at T0 versus T2 time: overall mean ER-40s and upright ER-40s (p = 0.041 and p = 0.032, respectively). Seven patients (63%) showed a slight increase in the mean MTT value during irradiation but no statistically significant differences in MTT parameters were found between T0, T1 and T2 (p > 0.05).
Conclusion
Using oesophageal scintigraphy we were able to detect early alterations of oesophageal transit during the third week of thoracic RT.
doi:10.1186/1471-230X-8-51
PMCID: PMC2611991  PMID: 18986522
10.  Reduced diversity and increased virulence-gene carriage in intestinal enterobacteria of coeliac children 
BMC Gastroenterology  2008;8:50.
Background
Coeliac disease is an immune-mediated enteropathology triggered by the ingestion of cereal gluten proteins. This disorder is associated with imbalances in the composition of the gut microbiota that could be involved in its pathogenesis. The aim of the present study was to determine whether intestinal Enterobacteriaceae populations of active and non-active coeliac patients and healthy children differ in diversity and virulence-gene carriage, so as to establish a possible link between the pathogenic potential of enterobacteria and the disease.
Methods
Enterobacteriaceae clones were isolated on VRBD agar from faecal samples of 31 subjects (10 active coeliac patients, 10 symptom-free coeliac patients and 11 healthy controls) and identified at species level by the API 20E system. Escherichia coli clones were classified into four phylogenetic groups A, B1, B2 and D and the prevalence of eight virulence-associated genes (type-1 fimbriae [fimA], P fimbriae [papC], S fimbriae [sfaD/E], Dr haemagglutinin [draA], haemolysin [hlyA], capsule K1 [neuB], capsule K5 [KfiC] and aerobactin [iutA]) was determined by multiplex PCR.
Results
A total of 155 Enterobacteriaceae clones were isolated. Non-E. coli clones were more commonly isolated in healthy children than in coeliac patients. The four phylogenetic E. coli groups were equally distributed in healthy children, while in both coeliac patients most commensal isolates belonged to group A. Within the virulent groups, B2 was the most prevalent in active coeliac disease children, while D was the most prevalent in non-active coeliac patients. E coli clones of the virulent phylogenetic groups (B2+D) from active and non-active coeliac patients carried a higher number of virulence genes than those from healthy individuals. Prevalence of P fimbriae (papC), capsule K5 (sfaD/E) and haemolysin (hlyA) genes was higher in E. coli isolated from active and non-active coeliac children than in those from control subjects.
Conclusion
This study has demonstrated that virulence features of the enteric microbiota are linked to coeliac disease.
doi:10.1186/1471-230X-8-50
PMCID: PMC2615025  PMID: 18983674
11.  The Helicobacter pylori duodenal ulcer promoting gene, dupA in China 
BMC Gastroenterology  2008;8:49.
Background
The prevalence of H. pylori is as high as 60–70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors.
Methods
H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1β polymorphism was investigated using restriction fragment length polymorphism.
Results
Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P < 0.05). Patients infected with dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1β polymorphisms.
Conclusion
In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.
doi:10.1186/1471-230X-8-49
PMCID: PMC2584642  PMID: 18950522
12.  Bones and Crohn's: Estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density 
BMC Gastroenterology  2008;8:48.
Background
Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis.
Aim
To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers.
Methods
111 male CD patients underwent osteodensitometry (DXA) of the spine (L1–L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls.
Results
Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD.
Conclusion
We found an altered hormonal status – i.e. E2 and, to a lesser extent T deficiency – in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.
doi:10.1186/1471-230X-8-48
PMCID: PMC2577678  PMID: 18947388
13.  Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion 
BMC Gastroenterology  2008;8:47.
Background
Partial External Biliary Diversion (PEBD) is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (AGS). PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome.
Methods
Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD.
Results
Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA), bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1) genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP) genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients.
Conclusion
Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.
doi:10.1186/1471-230X-8-47
PMCID: PMC2585081  PMID: 18937870
14.  Type and etiology of liver cirrhosis are not related to the presence of hepatic encephalopathy or health-related quality of life: a cross-sectional study 
BMC Gastroenterology  2008;8:46.
Background
Hepatic encephalopathy has a negative impact on health-related quality of life (QoL) in liver cirrhosis. There are scarce and conflicting data on whether type or etiology of liver cirrhosis could be related to hepatic encephalopathy in patients with cirrhosis. We aimed to determine the impact of cirrhosis etiology on hepatic encephalopathy and whether hepatic encephalopathy affects health-related QoL among patients with cirrhosis of different etiologies.
Methods
A total of 156 cirrhotic patients were prospectively evaluated for the presence of hepatic encephalopathy according to the West-Haven criteria as well as by means of two psychometric tests. Patients with cryptogenic cirrhosis or cirrhosis due to mixed hepatocellular/cholestatic etiologies were excluded. Fasting plasma glucose levels were also measured. QoL was evaluated by means of a validated questionnaire (SF-36).
Results
Diabetes mellitus was more common in patients with hepatocellular cirrhosis compared to those with cholestatic cirrhosis but the two groups did not differ in cirrhosis severity or the prevalence of hepatic encephalopathy (p > 0.05). The groups of patients with cirrhosis due to alcohol, hepatitis C, or cholestatic liver disease did not differ in severity of liver cirrhosis or the prevalence of hepatic encephalopathy (p > 0.05). Patients with cirrhosis of different etiologies did not differ in any SF-36 domain (p > 0.05). In multivariate analysis, performance at neuropsychological testing was independently related only to age, diabetes mellitus, and the Child-Pugh score whereas the SF-36 physical component summary only to the Child-Pugh score and hepatic encephalopathy.
Conclusion
Cirrhosis etiology does not seem to be related to hepatic encephalopathy or health-related QoL. Cognitive impairment is associated mainly with age, liver disease severity and diabetes mellitus.
doi:10.1186/1471-230X-8-46
PMCID: PMC2575200  PMID: 18922174
15.  Risk factors associated with non-alcoholic fatty liver disease in subjects from primary care units. A case-control study 
BMC Gastroenterology  2008;8:44.
Background
Non alcoholic fatty liver disease (NAFL) consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are associated with NAFL, such as, the metabolic syndrome factors, medications, bariatric surgery, nutritional disorders. However, very little information is available on the clinical relevance of this disorder as a health problem in the general population.
Methods and design
The aim of the study is establish the risk factors most frequently associated with NAFL in a general adult population assigned to the primary care units and to investigate the relationship between each component of the metabolic syndrome and the risk of having a NAFL.
A population based case-control, observational and multicenter study will be carried out in 18 primary care units from the "Area de Gestión del Barcelonés Nord y Maresme" (Barcelona) attending a population of 360,000 inhabitants and will include 326 cases and 370 controls. Cases are defined as all subjects fulfilling the inclusion criteria and with evidence of fatty liver in an abdominal ultrasonography performed for any reason. One control will be randomly selected for each case from the population, matched for age, gender and primary care center. Controls with fatty liver or other liver diseases will be excluded.
All cases and controls will be asked about previous hepatic diseases, consumption of alcohol, smoking and drugs, and a physical examination, biochemical analyses including liver function tests, the different components of the metabolic syndrome and the HAIR score will also be performed. Paired controls will also undergo an abdominal ultrasonography.
Discussion
This study will attempt to determine the factors most frequently associated with the presence of NAFL investigate the relationship between the metabolic syndrome and the risk of fatty liver and study the influence of the different primary care professionals in avoiding the evolution of the disease.
doi:10.1186/1471-230X-8-44
PMCID: PMC2569953  PMID: 18831772
16.  Determinants of female sexual function in inflammatory bowel disease: a survey based cross-sectional analysis 
BMC Gastroenterology  2008;8:45.
Background
Sexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects of low sexual function.
Methods
Women with IBD aged 18 to 65 presenting to the university departments of internal medicine and surgery were included. In addition, a random sample from the national patients organization was used (separate analyses). Sexual function was assessed by the Brief Index of Sexual Function in Women, comprising seven different domains of sexuality. Function was considered impaired if subscores were < -1 on a z-normalized scale. Results are presented as age adjusted odds ratios with 95% CI based on multiple logistic regression.
Results
336 questionnaires were included (219 Crohn's disease, 117 ulcerative colitis). Most women reported low sexual activity (63%; 17% none at all, 20% moderate or high activity). Partnership satisfaction was high in spite of low sexual interest in this group. Depressed mood was the strongest predictor of low sexual function scores in all domains. Urban residency and higher socioecomic status had a protective effect. Disease activity was moderately associated with low desire (OR 1.8, 95% CI 1.0 to 3.2). Severity of the disease course impacted most on intercourse frequency (OR 2.3, 95% CI 1.4 to 4.7). Lubrication problems were more common in smokers (OR 2.5, 95% CI 1.3 to 5.1).
Conclusion
Mood disturbances and social environment impacted more on sexual function in women with IBD than disease specific factors. Smoking is associated with lubrication problems.
doi:10.1186/1471-230X-8-45
PMCID: PMC2571095  PMID: 18834529
17.  The clinical overlap between functional dyspepsia and irritable bowel syndrome based on Rome III criteria 
BMC Gastroenterology  2008;8:43.
Background
Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). To date, no surveys have been performed to investigate the clinical overlap between these two disorders using Rome III criteria. Our aim was to investigate the prevalence and risk factors for the overlap of FD and IBS based on Rome III criteria in a large clinical sample.
Methods
Consecutive patients at the general gastroenterology outpatient clinic were requested to complete a self-report questionnaire. FD and IBS were defined by Rome III criteria.
Results
Questionnaires were returned by 3014 patients (52.8% female, 89% response rate). FD-IBS overlap was observed in 5.0% of the patients, while 15.2% and 10.9% of the patients were classified as FD alone and IBS alone, respectively. Compared with non-IBS patients, the odds ratio of having FD among IBS patients was 2.09 (95% CI: 1.68–2.59). Patients with FD-IBS overlap had higher severity scores for the postprandial fullness symptom (2.35 ± 1.49 vs. 1.72 ± 1.59, P < 0.001) and overall FD symptom (6.65 ± 2.88 vs. 5.82 ± 2.76, P = 0.002) than those with FD alone. The only independent risk factor for FD-IBS overlap vs. FD alone was the presence of postprandial fullness symptom (OR 2.67, 95% CI: 1.34–5.31).
Conclusion
Clinical overlap of FD and IBS according to Rome III criteria is very common. One risk factor for FD-IBS overlap is the presence of postprandial fullness symptom. This study provides clues for future pathophysiological studies of FD and IBS.
doi:10.1186/1471-230X-8-43
PMCID: PMC2569040  PMID: 18808723
18.  Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats 
BMC Gastroenterology  2008;8:42.
Background
Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.
Methods
120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg-1, CS 50 mg·kg-1, and CP 0.75 mg·kg-1 i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.
Results
Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (P < 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (P < 0.05), attenuated the down-regulation or up-regulation of the above index (P < 0.05). Treatment with CP decreased the survival rate on the 3rd day after reperfusion compared with group M(P < 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(P > 0.05).
Conclusion
Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.
doi:10.1186/1471-230X-8-42
PMCID: PMC2564972  PMID: 18808687
19.  Ultrasonographically detected gallbladder polyps: A reason for concern? A seven-year follow-up study 
BMC Gastroenterology  2008;8:41.
Background
The management of coincidental detected gallbladder polyps (GP) is still nebulous. There are few published data regarding their long-term growth. Objective of the present study was to investigate the prevalence and growth of gallbladder polyps in a survey of unselected subjects from the general population of a complete rural community.
Methods
A total of 2,415 subjects (1,261 women; 1,154 men) underwent ultrasound examination of the gallbladder, in November 1996 as part of a prospective study. Subjects in whom GP were detected at the initial survey underwent follow-up ultrasound examinations after 30 and 84 months.
Results
At the initial survey gallbladder polyps were detected in 34 subjects (1.4%; females: 1.1%, range 14 to 74 years; males: 1.7%, range 19 to 63 years). Median diameter was 5 ± 2.1 mm (range 2 to10 mm) at the initial survey, 5 mm ± 2.8 mm (range 2 to 12 mm) at 30 months and 4 ± 2.3 mm (range 2 to 9 mm) at 84 months. At the time of first follow-up no change in diameter was found in 81.0% (n = 17), reduction in diameter in 4.8% (n = 1) and increase in diameter in 14.3% (n = 3). At the time of second follow-up no increase in polyp diameter was found in 76.9% (n = 10) and reduction in diameter in 7.7% (n = 1). No evidence of malignant disease of the gallbladder was found.
Conclusion
Over a period of seven years little change was measured in the diameter of gallbladder polyps. There was no evidence of malignant disease of the gallbladder in any subject.
doi:10.1186/1471-230X-8-41
PMCID: PMC2553794  PMID: 18793401
20.  Resveratrol inhibits nonalcoholic fatty liver disease in rats 
BMC Gastroenterology  2008;8:40.
Background
The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α) production, lipid peroxidation and oxidative stress.
Methods
Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured.
Results
Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-α and MDA levels were significantly increased in the steatosis group (TNF-α; 33.4 ± 5.2 vs 26.24 ± 3.47 pg/ml and MDA; 9.08 ± 0.8 vs 3.17 ± 1.45 μM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05).
Conclusion
Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.
doi:10.1186/1471-230X-8-40
PMCID: PMC2547101  PMID: 18782455
21.  Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study 
BMC Gastroenterology  2008;8:39.
Background
Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.
Methods
Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume
Results
100 measurements in 50 patients (33 m/17 w; age 56 years (± 8); Child-Pugh-score 12 (± 2), serum creatinine 256 μmol (± 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m2 (± 138) despite CVP within the normal range (11 mmHg (± 5). After infusion, GEDVI, CI and CVP increased (682 ml/m2 (± 128) vs. 744 ml/m2 (± 171), p < 0.001; 4.3 L/min/m2 (± 1.1) vs. 4.7 L/min/m2 (± 1.1), p < 0.001; 12 mmHg (± 6) vs. 14 mmHg (± 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm5/m2 (± 1144) vs. 1490 dyn s/cm5/m2 (± 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r2 = 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.
Conclusion
In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.
doi:10.1186/1471-230X-8-39
PMCID: PMC2556671  PMID: 18752670
22.  Validation of a survey methodology for gastroesophageal reflux disease in China 
BMC Gastroenterology  2008;8:37.
Background
Gastroesophageal reflux disease (GERD) causes a wide range of clinical symptoms and potentially serious complications, but epidemiological data about GERD in China are limited. The aim of this pilot study was to develop and validate a methodology for the epidemiological study of GERD in China.
Methods
Regionally stratified, randomized samples of Shanghai residents (n = 919) completed Mandarin translations of the Reflux Disease Questionnaire (RDQ), GERD Impact Scale, Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire and 36-item Short Form Health Survey (SF-36). Reliability and construct validity were tested by appropriate statistical analyses.
Results
The response rate was 86%. The test-retest reliability coefficients for the RDQ, GERD Impact Scale, QOLRAD and SF-36 were 0.80, 0.71, 0.93 and 0.96, respectively, and Cronbach's alpha coefficients were 0.86, 0.80, 0.98 and 0.90, respectively. Dimension scores were highly correlated with the total scores for the QOLRAD and SF-36, and factor analysis showed credible construct validity for the RDQ, GERD Impact Scale and SF-36. The RDQ GERD score was significantly negatively correlated with QOLRAD dimensions of food and drink problems and social functioning, and was significantly negatively correlated with all dimensions of the SF-36. All eight of the SF-36 dimensions were significantly correlated with the QOLRAD total score.
Conclusion
This study developed and tested a successful survey methodology for the investigation of GERD in China. The questionnaires used demonstrated credible reliability and construct validity, supporting their use in larger epidemiological surveys of GERD in China.
doi:10.1186/1471-230X-8-37
PMCID: PMC2533006  PMID: 18717991
23.  Erythromycin lacks colon prokinetic effect in children with functional gastrointestinal disorders: a retrospective study 
BMC Gastroenterology  2008;8:38.
Background
Motilin, a peptide hormone has a direct excitatory effect on circular smooth muscle strips derived from the human colon. Reduced plasma motilin concentration has been reported in adults with chronic constipation. Erythromycin, a non-peptide motilin receptor agonist, induces phase 3 of the migrating motor complex (MMC) in the antro-duodenum and also reduces oro-cecal transit time. A pediatric study has reported an improvement in clinical symptoms of constipation following erythromycin administration, but the effect on colon motility in children has not been formally evaluated. We used colon manometry to study the effect of intravenous erythromycin lactobionate at 1 mg/kg on colon motiltiy in ten children.
Methods
We selected patients with normal antroduodenal and colon manometry studies that were performed simultaneously. All studies were performed for clinically indicated reasons. We quantified the effect of erythromycin on colon contraction by calculating the area under the curve (AUC).
Results
The mean (SE of mean) AUC in the colon during the fasting, post-erythromycin and postprandial phases of the study was 2.1 mmHg/sec (0.35), 0.99 mmHg/sec (0.17) and 3.05 mmHg/sec (0.70) respectively. The AUC following erythromycin was significantly less compared to the fasting phase of the study (p < 0.01).
Conclusion
Erythromycin lacks colon prokinetic effect in children with chronic constipation evaluated by colon manometry.
doi:10.1186/1471-230X-8-38
PMCID: PMC2529327  PMID: 18718006
24.  Correlation between CD4 counts of HIV patients and enteric protozoan in different seasons – An experience of a tertiary care hospital in Varanasi (India) 
BMC Gastroenterology  2008;8:36.
Background
Protozoan infections are the most serious among all the superimposed infections in HIV patients and claim a number of lives every year. The line of treatment being different for diverse parasites necessitates a definitive diagnosis of the etiological agents to avoid empirical treatment. Thus, the present study has been aimed to elucidate the associations between diarrhoea and CD4 counts and to study the effect of HAART along with management of diarrhoea in HIV positive patients. This study is the first of its kind in this area where an attempt was made to correlate seasonal variation and intestinal protozoan infestations.
Methods
The study period was from January 2006 to October 2007 wherein stool samples were collected from 366 HIV positive patients with diarrhea attending the ART centre, inpatient department and ICTC of S.S. hospital, I.M.S., B.H.U., Varanasi. Simultaneously, CD4 counts were recorded to assess the status of HIV infection vis-à-vis parasitic infection. The identification of pathogens was done on the basis of direct microscopy and different staining techniques.
Results
Of the 366 patients, 112 had acute and 254 had chronic diarrhea. The percentages of intestinal protozoa detected were 78.5% in acute and 50.7% in chronic cases respectively. Immune restoration was observed in 36.6% patients after treatment on the basis of clinical observation and CD4 counts. In 39.8% of HIV positive cases Cryptosporidium spp. was detected followed by Microsporidia spp. (26.7%). The highest incidence of intestinal infection was in the rainy season. However, infection with Cyclospora spp. was at its peak in the summer. Patients with chronic diarrhea had lower CD4 cell counts. The maximum parasitic isolation was in the patients whose CD4 cell counts were below 200 cells/μl.
Conclusion
There was an inverse relation between the CD4 counts and duration of diarrhea. Cryptosporidium spp. was isolated maximum among all the parasites in the HIV patients. The highest incidence of infection was seen in the rainy season.
doi:10.1186/1471-230X-8-36
PMCID: PMC2536662  PMID: 18713475
25.  Immunohistochemical testing for Helicobacter Pylori existence in neoplasms of the colon 
BMC Gastroenterology  2008;8:35.
Background
Helicobacter pylori is a common pathogen, and its prevalence varies with socioeconomic conditions (10–80%). It has recently been recognized as a class I carcinogen in relation to gastric cancer. The aim of this study was to investigate the presence of Helicobacter pylori in neoplasms of the colon by immunohistochemical methods.
Methods
The polypectomy materials of 51 patients (19 male and 32 female) who had undergone colonoscopic polypectomy were retrieved for retrospective examination. The endoscopic size and colonic localization of the polyps were recorded. Hematoxylin and eosin stains were evaluated according to histological type and grade of dysplasia. Biopsy stains were immunohistochemically treated with Helicobacter pylori antibodies by the streptavidine-biotin immunoperoxidase technique. Helicobacter pylori staining in the gastric mucosa was used as the control for the immunohistochemical method. Specimens were classified according to the presence of Helicobacter pylori under an optical microscope, and Helicobacter pylori positive specimens were stratified according to the respective staining pattern.
Results
Mean age was 61.88 ± 10.62 (40–82) years. Polyp sizes were 1.45 ± 0.92 (1–4) cm; and 25.5% of polyps were localized in the right colon, 68.6% in the left colon and 5.9% in the transverse colon. Presence of Helicobacter pylori was not correlated with localization (p > 0.05) or size of the polyps (p > 0.05).
Eleven (21.6%) of all specimens included in the study were Helicobacter pylori positive by immunohistochemical methods. Of the Helicobacter pylori positive specimens, the staining pattern was diffuse: Equivocal in 90.9%, nonspecific with a finely granular type concentrated on the luminal surface in 90.9%, dot-like granular in 54.5%, and spiral in 9.1%. Of the tubular polyps, 17.9% were H. pylori positive, and the staining pattern was equivocal in 100%, luminal in 85.7%, and dot-like granular in 57.1%. Of the villous polyps, 60% were H. pylori positive, and the staining pattern was inconclusive in 66.7%, luminal in 100%, dot-like granular in 33.3%, and spiral in 33.3%. Of the cancerous cases, 25% were H. pylori positive and showed an equivocal, luminal, and dot-like granular staining pattern. No significant correlation was determined between histologic types and prevalence of H. pylori (p > 0.05).
Conclusion
The presence of H. pylori in colon polyps did not yield any correlation with polyp size, colonic localization or histopathologic type. The higher rate of H. pylori positivity in villous polyps does not present a causal relationship. We were able to determine H. pylori existence in colon polyps by immunohistochemical methods, albeit with no statistical significance.
doi:10.1186/1471-230X-8-35
PMCID: PMC2527302  PMID: 18702825

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