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"Drop in" gastroscopy outpatient clinic - experience after 9 months
Background, Logistics handling referrals for gastroscopy may be more time consuming than the examination itself. For the patient, "drop in" gastroscopy may reduce uncertainty, inadequate therapy and time off work.Methods, After an 8-9 month run-in period we asked patients, hospital staff and GPs to fill in a questionnaire to evaluate their experience with "drop in" gastroscopy and gastroscopy by appointment, respectively. The diagnostic gain was evaluated.Results, 112 patients had "drop in" gastroscopy and 101 gastroscopy by appointment. The number of "drop in" patients varied between 3 and 12 per day (mean 6.5). Mean time from first GP consultation to gastroscopy was 3.6 weeks in the "drop in" group and 14 weeks in the appointment group. The half-yearly number of gastroscopies increased from 1148 before introducing "drop in" to 1472 after (28% increase) and the proportion of examinations with pathological findings increased from 36% to 48% Patients and GPs expressed great satisfaction with "drop in". Hospital staff also acclaimed although it caused more unpredictable working days with no additional staff.Conclusions, "Drop in" gastroscopy was introduced without increase in staff. The observed increase in gastroscopies was paralleled by a similar increase in pathological findings without any apparent disadvantages for other groups of patients. This should legitimise "drop in" outpatients gastroscopies, but it requires meticulous observation of possible unwanted effects when implemented.Key Words: endoscopy, gastroscopy, outpatient clinic, waiting lists
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Long-term effects of treatment and response in patients with chronic hepatitis C on quality of life
Background Hepatitis C decreases health related quality of life (HRQL) which is further diminished by antiviral therapy. HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study).Methods The Short Form (SF)-36 Health Survey was administered at baseline (n= 192) and 24 weeks after the end of therapy (n= 128).Results At baseline HRQL was influenced by age, participating center, severity of liver disease and income. Exploring the course of HRQL (scores at follow up minus baseline), only the dimension general health increased. In this dimension patients with a relapse or sustained response differed from non-responders. Men and women differed in the dimension bodily pain. Treatment schedule did not influence the course of HRQL.Conclusions Main determinants of HRQL were severity of liver disease, age, gender, participating center and response to treatment. Our results do not exclude a more profound negative impact of individualized treatment compared to standard, possibly caused by higher doses and extended treatment duration in the individualized group. Antiviral therapy might have a more intense and more prolonged negative impact on females.
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Serological Assessment of gastric mucosal Atrophy in gastric Cancer.
Background:
Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1(PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia.
Methods:
Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Lauren type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed.
Results:
Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p=0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p=0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p<0.01). Lauren-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio.
Conclusions:
Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.
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Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells
Background:
Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables. We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in HT-29 cells.
Methods:
In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without 60 micromol/L luteolin and/or 10 nmol/L IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, [3H]thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II, the protein expression and activation of IGF-IR, and the association of the p85 subunit of phophatidylinositol-3 kinase (PI3K) with IGF-IR, the phosphorylation of Akt and extracellular signal-regulated kinase (ERK)1/2, and cell division cycle 25c (CDC25c), and PI3K activity.
Results:
Luteolin (0 - 60 micromol/L) dose-dependently reduced the IGF-II secretion of HT-29 cells. IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition. Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts. Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR. Additionally, luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt, ERK1/2, and CDC25c in the presence and absence of IGF-I stimulation.
Conclusions:
The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest.
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Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: a retrospective multicenter chart review study
Background:
Carbon labeled urea breath tests usually entail a two point sampling with a 20 to 30-minute gap. Our aim was to evaluate the duration of time needed for diagnosing Helicobacter pylori by the BreathID(R) System.
Methods:
This is a retrospective multicenter chart review study. Test location, date, delta over baseline, and duration of the entire test were recorded. Consecutively 13C urea breath tests results were extracted from the files over a nine year period.
Results:
Of the 12,791 tests results, 35.1% were positively diagnosed and only 0.1% were inconclusive. A statistically significant difference in prevalence among the countries was found: Germany showing the lowest, 13.3%, and Israel the highest, 44.1%. Significant differences were found in time to diagnosis: a positive diagnosis had the shortest and an inconclusive result had the longest. Overall test duration averaged 15.1 minutes in Germany versus approximately 13 minutes in other countries. Diagnosis was achieved after approximately 9 minutes in Israel, Italy and Switzerland, but after 10 on average in the others. The mean delta over baseline value for a negative diagnosis was 1.03 +/- 0.86, (range, 0.9 - 5), versus 20.2 +/- 18.9, (range, 5.1 - 159.4) for a positive one.
Conclusions:
The BreathID(R) System used in diagnosing Helicobacter pylori can safely shorten test duration on average of 10-13 minutes without any loss of sensitivity or specificity and with no test lasting more than 21 minutes.
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Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts
Background:
Baseline low platelet count (<150,000/uL) increases the risk of on-treatment severe thrombocytopenia (platelet count <50,000/uL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia.
Methods:
Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy.
Results:
Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count <100,000/uL and rapid early platelet decline (>30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (P<0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT [greater than or equal to] 100,000/uL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count <100,000/uL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%).
Conclusions:
For patients with CHC on antiviral therapy, baseline platelet counts <100,000/uL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.
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GDNF protects enteric glia from apoptosis: evidence for an autocrine loop
Background:
Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis.
Methods:
GDNF expression and EGC apoptosis were determined by immunofluorescence using specimen from CD patients. In primary rat EGC cultures, GDNF receptors were assessed by western blot and indirect immunofluorescence microscopy. Apoptosis in cultured EGC was induced by TNF-alpha and IFN-gamma, and the influence of GDNF on apoptosis was measured upon addition of GDNF or neutralizing anti-GDNF antibody.
Results:
Increased GDNF expression and Caspase 3/7 activities were detected in specimen of CD patients but not in healthy controls. Moreover, inactivation of GDNF sensitized in EGC cell to IFN-gamma/TNF-alpha induced apoptosis.
Conclusions:
This study proposes the existence of an autocrine anti-apoptotic loop in EGC cells which is operative in Crohn's disease and dependent of GDNF. Alterations in this novel EGC self-protecting mechanism could lead to a higher susceptibility towards apoptosis and thus contribute to disruption of the mucosal integrity and severity of inflammation in CD.
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Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study
Background:
The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort.
Methods:
In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.
Results:
Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165).
Conclusion:
In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.
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High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells
Background:
Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal beta-cell line, INS-1E.
Methods:
The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.
Results:
Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 uM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.
Conclusions:
Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.
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Prevalence of non Helicobacter pylori species in patients presenting with dyspepsia
Background:
Helicobacter species associated with human infection include Helicobacter pylori, Helicobacter heilmannii and Helicobacter felis among others. In this study we determined the prevalence of H. pylori and non-Helicobacter pylori organisms H. felis and H. heilmannii and analyzed the association between coinfection with these organisms and gastric pathology in patients presenting with dyspepsia. Biopsy specimens were obtained from patients with dyspepsia on esophagogastroduodenoscopy (EGD) for rapid urease test, histology and PCR examination for Helicobacter genus specific 16S rDNA, H. pylori phosphoglucosamine mutase (glmM) and urease B (ureB) gene of H. heilmannii and H. felis. Sequencing of PCR products of H. heilmannii and H. felis was done.
Results:
Two hundred-fifty patients with dyspepsia were enrolled in the study. The mean age was 39+/- 12 years with males 162(65%). Twenty-six percent (66 out of 250) were exposed to cats or dogs. PCR for Helicobacter genus specific 16S rDNA was positive in 167/250 (67%), H. pylori glmM in 142/250 (57%), H. heilmannii in 17/250 (6%) and H. felis in 10/250 (4%), respectively. All the H. heilmannii and H. felis PCR positive patients were also positive for H. pylori PCR amplification. The occurrence of coinfection of H. pylori and H. heilmannii was 17(6%) and with H. felis was 10(4%), respectively. Only one out of 66 exposed to pets were positive for H. heilmannii and two for H. felis. Histopathology was carried out in 160(64%) of 250 cases. Chronic active inflammation was observed in 53(56%) (p= 0.001) of the patients with H. pylori infection alone as compared to 3(37%) (p= 0.73) coinfected with H. heilmannii and H. pylori and 3(60%) coinfected with H. felis and H. pylori (p=0.66). Intestinal metaplasia was observed in 3(3%)(p=1.0) of the patients with H. pylori infection alone as compared to 2(25%) (p=0.02) coinfected with H. heilmannii and H. pylori and 1(20%) coinfected with H. felis and H. pylori (p=0.15).
Conclusion:
The prevalence of H. heilmannii and H. felis was low in our patients with dyspepsia. Exposure to pets did not increase the risk of H. heilmannii or H. felis infection. The coinfection of H. pylori with H. heilmannii was seen associated with intestinal metaplasia, however this need further confirmation.
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