Activation of purinergic receptors by ATP stimulates Cl- efflux in biliary epithelial cells. To determine whether purinergic agonists are present under physiological conditions, we have assayed mammalian bile for nucleotides and assessed whether hepatoma and cholangiocarcinoma cell lines are capable of nucleotide release. Bile samples were collected from human, rat, and pig donors and assayed for nucleotide concentrations by luminometry. ATP, ADP, and AMP were present in bile from each species, and the average total nucleotide concentration in human bile was 5.21 +/- 0.91 microM (n = 16). In an in vitro model of HTC rat hepatoma cells or Mz-ChA-1 cholangiocarcinoma cells on a superfused column, nucleotides were present in the effluent from each cell type. Addition of alpha, beta-methyleneadenosine 5'-diphosphate (50 microM) to inhibit 5'-nucleotidase activity increased AMP concentrations two- to threefold. Exposure to forskolin (100 microM) or ionomycin (2 microM) stimulated nucleotide release from cholangiocarcinoma but not hepatoma cells. These studies indicate that adenosine nucleotides are present in bile in concentrations sufficient to activate purinergic receptors. Purinergic receptor activation by local nucleotide release might constitute an autocrine and/or paracrine mechanism for modulation of biliary secretion.
An etiology was identified in the majority of patients with unexplained pancreatitis. SOD represented the most common finding. Moderate to severe chronic pancreatitis was found in over one-fifth of these patients. Bile analysis, SOM, and EUS are useful tools in the evaluation of unexplained acute pancreatitis.
SUMMARY A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to nitrites was closely related to the occurrence of nitrate-reducing bacteria. In three patients the intragastric milieu had returned to normal two months after cimetidine treatment had been discontinued. Mean nitrite and N-nitrosamine concentrations did not return to pre-treatment levels in the group of eight patients who remained on maintenance cimetidine (0.4 g at night-time) for three months after the full dose treatment. This study shows that cimetidine treatment can create an intragastric milieu resembling that of atrophic gastritis. Large scale and long-term studies are necessary to establish whether these findings have any clinical significance.
Patients with pernicious anaemia are generally considered to have a risk of developing gastric carcinoma three to four times higher than that of control patients.1-6 The annual incidence of gastric carcinoma in 7patients with pernicious anaemia is around 1%. Gastroscopy (with biopsy and cytology) is the technique of choice for the diagnosis of carcinoma, which has an improved prognosis when detected at an early stage. There are few reports of endoscopy in patients with pernicious anaemia.810 Gastric carcinoma and polyps have been investigated but little attention has been paid to mucosal dysplasia, which might have important prognostic significance.The present study was performed to assess the prevalence of benign, dysplastic and neoplastic lesions in a group of patients with pernicious anaemia, to compare the relative merits of histological and cytological methods for the detection of
The development of gastric dysplasia and neoplasia in patients with pernicious anaemia has been evaluated in a prospective clinical and endoscopic follow up study. After Because a close association has been described between atrophic gastritis and intestinal metaplasia and the development of gastric carcinoma,' these are now considered to be precancerous lesions.6 In pernicious anaemia, chronic atrophic gastritis with intestinal metaplasia is common, and gastric polyps are frequently found.7 ' -Endoscopic screening of patients with this disorder showed a high incidence of gastric mucosal dysplasia,9'0 and pernicious anaemia is therefore assumed to be a precancerous condition.
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