Assessment of response to beta-blockers by expression of ßArr2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients.

BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS: Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge. Transcription and protein expression of Ras homolog family member A (RhoA), Rho-kinase (ROCK)2, beta-arrestin2 (ßArr2), endothelial nitric oxide synthase (eNOS) and the phosphorylation of downstream effectors VASP and moesin were analyzed using PCR and Western blot. Further 21 patients on NSBB were evaluated on their follow up for events of variceal bleeding defined as non-response. RESULTS: Ten patients showed HVPG <10mmHg, further seven patients showed significant hemodynamic response to NSBB, whereas eight patients were non-responders. The mucosal transcription of vasoactive proteins was higher in antrum mucosa compared to corpus and duodenum. The transcriptional levels of vasoactive proteins were higher in patients with HVPG >10mmHg and HVPG >16mmHg. Interestingly, mRNA levels of RhoA and ROCK2 were lower in patients with large varices at endoscopy. Moreover, RhoA and ROCK2 transcription correlated with the decrease of HVPG after acute NSBB challenge. Finally, acute and long-term non-responders showed lower expression of ßArr2 in antrum mucosa. CONCLUSION: This study shows for the first time that the expression of ßArr2 in antrum mucosa biopsies might reflect the hemodynamic response to NSBB and their long-term protective effect. This finding might offer an easy approach at upper endoscopy to facilitate the decision to treat with NSBB if varices are present.

A low cost rapid urease test to detect Helicobacter pylori infection in resource limited settings.

The aim of the study was to evaluate the suitability of a modified one minute rapid urease test (one day rapid urease test) as a low cost H. pylori detection method. A sample of 205 patients clinically suspected of having H. pylori infection was tested. One day rapid urease test and histology based H. pylori tests (the gold standard) were performed on endoscopic antral biopsies. There were 6 true positives, 191 true negatives, 8 false positives and zero false negatives. The sensitivity, specificity and positive (PPV) and negative predictive values (NPV) of the test were 100%, 96%, 42.9%, and 100% respectively. The cost per patient was 0.3US$. High sensitivity, specificity and NPV, low cost and simplicity of method were the advantages of the test and the main limitation was low PPV. Hence, one day rapid urease test can be considered as a suitable low cost method to detect H. pylori infection in resource limited settings.

Ultrasonographic assessment of fasting liquid content in the human stomach.

BACKGROUND: Disturbed antroduodenal motility plays an important role in the pathophysiology of functional dyspepsia (FD). Such motility disturbances can be investigated by transcutaneous ultrasound. When it is measured in a standardized section, patients with FD have on an average significantly larger antral area than healthy controls. METHODS: In this study we investigated the relationship between the antral area measured by ultrasound and the amount of fasting gastric content quantitated by aspiration through the gastroscope in 30 patients. In five healthy controls we measured the increment of the antral area after ingestion of graded volumes of water. All recordings were made in interdigestive phase I. RESULTS: Measurements of the antral area were highly reproducible, with small variations within an hour and from day to day. There was a highly significant correlation between ultrasonographically measured antral area and amount of fasting gastric juice and between increment of antral area and amounts of ingested water. CONCLUSIONS: The ultrasonographically measured antral area during fasting is highly reproducible. Enlarged fasting antral area reflects increased volume of gastric juice.