Characterization of immune receptor-cognate ligands expression and signalling pathways in human intestinal myofibroblasts

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Exploring the agreement between diagnostic criteria for IBS in primary care in Greece

<p>Abstract</p> <p>Background</p> <p>Irritable Bowel Syndrome (IBS) is frequently diagnosed in primary care. Its diagnosis is based on diagnostic criteria but their use is limited in primary care.</p> <p>We aimed to assess the diagnostic agreement between the older (Manning's and Rome II) and the new (Rome III) criteria for the diagnosis of IBS in primary care in Greece.</p> <p>Methods</p> <p>Medical records of 5 Health Centers in rural Crete, Greece, were reviewed for a four-year period and patients with the diagnosis of IBS were invited to a structured interview. Kappa agreement of the Rome III criteria with the criteria of Manning and Rome II was estimated. One hundred and twenty three patients were eligible for interview and 67 (54.5%) participated. Forty-six (69%) fulfilled the Manning, 32(48%) the Rome II, and 16(24%) the Rome III criteria. Twenty-seven (40%) patients were identified as IBS according to the questionnaire for the identification of functional gastrointestinal diseases (FGIDs). The agreement of Rome III with Manning criteria was poor (kappa = 0.25). The agreement between the FGIDs questionnaire and the Manning, Rome II and Rome III criteria was: kappa = 0.30, 0.31 and 0.24 respectively. Moderate agreement was found between the Rome II and III criteria (kappa = 0.51).</p> <p>Conclusion</p> <p>Questionnaires and criteria deriving from expert's consensus meetings or tertiary hospitals are not easy to apply in rural primary care where symptoms are often underestimated by patients and complicated questions can be confusing.</p

Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM(1)) in hepatitis C seropositive subjects on Crete, Greece

BACKGROUND: Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV) has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C. PATIENTS AND METHODS: One hundred and forty two patients (59 men and 83 women), who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women), which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL) technique on human epithelial cells from larynx cancer (HEp-2 cells), rat liver-kidney-stomach substrate (CT3) and Chrithidia Luciliae (CL). RESULTS: Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA), positive in 72 patients (50.7%). Anti-smooth muscle antibodies (ASMA) were detected in 33 patients (23.2%). Only one patient was positive for LKM(1) autoantibodies. No autoantibodies were found in 38 patients (26.7%). Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%). CONCLUSIONS: Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM(1) autoantibodies are exceptionally rare in these patients

Upper gastrointestinal endoscopy for dyspepsia: Εxploratory study of factors influencing patient compliance in Greece

BACKGROUND: Upper gastrointestinal endoscopy is the most preferable diagnostic examination for patients over fifty when upper gastrointestinal symptoms appear. However, limited knowledge exists in concerns to the compliance of primary care patients' to the doctors' recommendations for endoscopy. METHODS: Patients who visited primary care practices in Greece and experienced upper gastrointestinal symptoms within a 10 days screening study, were referred for an upper endoscopy exam. The patients which refused to complete the endoscopy exam, were interviewed by the use of an open- ended translated and validated questionnaire, the Identification of Dyspepsia in General Population (IDGP) questionnaire. A qualitative thematic analysis grounded on the theory of planned behavior was performed to reveal the reasons for patients' refusal, while socio-demographic predictors were also assessed. RESULTS: Nine hundred and ninety two patients were recorded, 159 of them (16%) were found positive for dyspepsia and gastro-esophageal reflux disease according to the IDGP questionnaire. Out of the above, 131 (83.6%) patients refused further investigation with endoscopy. Patients who refused upper endoscopy were predominantly female (87.8%) (p = 0.036) and over the age of 50. The lack of severe symptoms, fear of pain, concerns of sedation, comorbidity and competing life demands were reported by patients as barriers to performing an endoscopic investigation. CONCLUSIONS: Patients with dyspepsia in rural Greece tend to avoid upper gastrointestinal endoscopy, with two major axons considered to be the causes of patients' refusal: their beliefs towards endoscopy and their personal capability to cope with it. Future research examining reasons of low compliance should be carried out in combination with modern behavioral theories so as to investigate into the above

Influence of hepatitis G virus infection on liver disease

The influence of hepatitis G virus (HGV) infection on disease activity in hepatitis C related and unrelated liver disease was investigated in 254 individuals using an EIA polymerase chain reaction assay for HGV. One hundred patients had chronic hepatitis C, 26 primary biliary cirrhosis, and 30 alcoholic liver cirrhosis. In addition, 51 hepatitis B surface antigen (HBsAg)-positive and 47 anti-hepatitis C virus (HCV)-positive blood donors were screened. Hepatitis G virus was detected in 18% of patients with chronic hepatitis C, 13% of patients with alcoholic liver cirrhosis, 11 % of patients with primary biliary cirrhosis, 10% of anti-HCV-positive blood donors, and 2% of HBsAg-positive blood donors. Virus load and alanine aminotransferase (ALT) levels did not differ significantly in patients with HCV alone versus patients coinfected with HCV and HGV. However, mild liver fibrosis correlated with HGV coinfection. Hepatitis G virus did not influence ALT levels or liver damage in liver disease unrelated to viral infectio

Optimized detection of circulating anti-nuclear envelope autoantibodies by immunofluorescence

BACKGROUND: Antinuclear antibodies are useful diagnostic tools in several autoimmune diseases. However, the routine detection of nuclear envelope autoantibodies using immunofluorescence (IF) is not always easy to perform in patients' sera because of the presence of autoantibodies to other nuclear and cytoplasmic components which could mask the characteristic rim-like pattern of nuclear envelope autoantibodies. This is particularly common in sera from patients with primary biliary cirrhosis (PBC), which generaly have high titres of anti-mitochondrial antibodies. Therefore, we have assayed a number of commercial slides and alternative fixation conditions to optimize the detection of anti-nuclear envelope antibodies (ANEA) in PBC sera. METHODS: We have explored the presence of ANEA in 33 sera from patients with established PBC using three different Hep2 commercial slides and home-made slides with HeLa and Hep2 cells fixed with methanol, ethanol, 1% or 4% formaldehyde. RESULTS: We observed that the IF pattern was related to the cell type used (Hep2 or HeLa), the manufacturer and the cell fixation scheme. When both cell lines were fixed with 1% formaldehyde, the intensity of the cytoplasmic staining was considerably decreased regardless to the serum sample, whereas the prevalence of cytoplasmic autoantibodies was significantly lowered, as compared to any of the Hep2 commercial slide and fixation used. In addition, the prevalence of ANEA was importantly increased in formaldehyde-fixed cells. CONCLUSION: Immunofluorescence using appropriately fixed cells represent an easy, no time-consuming and low cost technique for the routine screening of sera for ANEA. Detection of ANEA is shown to be more efficient using formaldehyde-fixed cells instead of commercially available Hep2 cells

Prevalence of hepatitis B and C markers in high-risk hospitalised patients in Crete: a five-year observational study

BACKGROUND: So far the prevalence of viral hepatitis infection in hospitalized patients has not been extensively studied. Therefore we conducted the present five-year observational study to evaluate the prevalence of HBV and HCV infection in high-risk hospitalized patients of Crete, the largest Greek island, Due to the homogeneous population, epidemiological studies can be accurately done. METHODS: The study was carried out in two out of four District General Hospitals, and in the University Hospital of the island. Markers for HBV and HCV were studied and statistically evaluated according to age, sex and geographical area, in a well-defined hospitalized population. RESULTS: The total prevalence of HBsAg and anti-HCV in the three prefectures during the five-year study is 2.66% and 4.75% respectively. Overall the relative risks were higher in males than females for each hepatitis marker (p < 0.001). Higher prevalence of HBcAb was found in the 41–60 years age group for both sexes (males 36.17%, females 27.38%). Peak HBsAg prevalence was found in the age group of 21–40 and 41–60 years for males (5.4%) and females (3.09%) respectively. Anti-HCV prevalence increases with age reaching the highest prevalence in the age group of 41–60 years for males (7.19%) and in the 61–90 years age group for females (7.16%). For both sexes significant differences between the three locations were identified. For HBsAg a higher prevalence in Heraklion (3.96%) compared to Chania (2.30%, males: p < 0.0001, females: p < 0.05) and Rethymnon (1.45%, males: p < 0.01, females: p < 0.0001) was detected. For HCV a significantly higher prevalence in Heraklion (6.54%) compared to Chania (2.39%, males: p < 0.001, females: p < 0.001) but not in Rethymnon (5.15%, NS). A lower prevalence rate of HBcAb in Heraklion compared to Chania (20.07% versus 23.05%, males: p < 0.001, females: p < 0.001) was found. CONCLUSIONS: These results were possibly overestimated, but nevertheless reflect the situation of the general population within the island as shown by our previous publications in other study groups. Moreover they contribute to the mapping of viral hepatitis prevalence in a geographical area of Southern Europe and may be helpful in planning public health interventional strategies

Octreotide and hepatocellular carcinoma

[No abstract available

The type I insulin-like growth factor regulates the liver stromal response to metastatic colon carcinoma cells.

Hepatic stellate cells (HSC) play a major role in initiating the liver fibrogenic (wounding) response of the liver and can also orchestrate a pro-metastatic microenvironment in the liver in response to invading cancer cells. Here we explored the role of the hepatic stellate cells in colon carcinoma liver metastasis with emphasis on the contribution of the insulin-like growth factor (IGF) axis to their activation and function. To this end, we used mice with a Tamoxifen inducible liver IGF-I deficiency. We found that in mice with a sustained IGF-I deficiency, recruitment and activation of HSC into tumor-infiltrated areas of the liver were markedly diminished, resulting in decreased collagen deposition and reduced tumor expansion. In addition, IGF-I could rescue HSC from apoptosis induced by pro-inflammatory factors such as TNF-α known to be upregulated in the early stages of liver metastasis. Moreover, in surgical specimens, activated IGF-IR was observed on HSC-like stromal cells surrounding colorectal carcinoma liver metastases. Finally, IGF-targeting in vivo using an IGF-Trap caused a significant reduction in HSC activation in response to metastatic colon cancer cells. Therefore, our data identify IGF as a survival factor for HSC and thereby, a promoter of the pro-metastatic microenvironment in the liver. IGF-targeting could therefore provide a strategy for curtailing the pro-metastatic host response of the liver during the early stages of liver metastasis

Interleukin 1 is a key driver of inflammatory bowel disease-demonstration in a murine IL-1Ra knockout model

Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). The balance between IL-1 and IL-1Ra as a natural inhibitor plays a vital role in a variety of diseases. Here, we investigated whether changes seen during IBD are induced spontaneously in mice lacking a functional IL-1rn gene. Histological staining was performed on the jejunum and ileum of BALB/c IL-1rn+/+ and IL-1rn-/- mice to characterize crypt-villus height, villus width, and number of goblet cells per villus. Pro-inflammatory cytokines, immune cell infiltration and matrix-degrading enzymes, together with the production of intestinal enzymes and the integrity of tight and adherent junction proteins were determined using immunohistochemistry. In the small intestine of BALB/c IL-1rn-/- mice the villus heights were significantly reduced; and in the ileum this was accompanied by a decrease in villi width. There was also an increase in goblet cell number and mucin production compared to wild-type mice. IL-1α and IL-1β immunopositivity were increased, whilst IL-1R1 expression was decreased in IL-1rn-/- mice. IL-15 and TNFα were also increased in older IL-1rn-/- mice. Increased polymorphonuclear and macrophage infiltration were seen in IL-1rn-/- mice, whilst expression of matrix-degrading enzymes and digestive enzymes were unchanged, except for dipeptidyl peptidase IV which was increased in younger IL-1rn-/- mice compared to wild type mice. The expression of tight and adhesion junctions were also dramatically decreased in IL-1rn-/- mice. In conclusion, IL-1rn-/- mice developed spontaneous abnormalities which displayed features associated with IBD, demonstrating a clear role for IL-1 in IBD