Omeprazole and CYP2C19 polymorphism: effects of long-term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders.

BACKGROUND: The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short-term treatment. AIM: To investigate the relationship between CYP2C19 genotype and the effects of long-term omeprazole treatment. MATERIAL AND METHODS: A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods. RESULTS: In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long-term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean +/- s.e.) were both about threefold higher in the wild type/mutated (52.1 +/- 7.6 pM and 7.3 +/- 1.3 nM (n=19), respectively) compared to wild type/wild type (14. 7 +/- 0.9 pM and 2.5 +/- 0.1 nM (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long-term treatment, both gastrin and chromogranin A were high (88 pM and 13.7 nM, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long-term treatment, compared with the corresponding wild type/wild type (n=49) group (147 +/- 19 microg/L vs. 193 +/- 12 microg/L, P=0. 04). CONCLUSION: Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long-term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual's capacity to metabolize omeprazole.

Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism.

BACKGROUND & AIMS: Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabolizers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of the CYP2C19 polymorphism for the effects of omeprazole on intragastric pH and plasma gastrin concentrations has been investigated. METHODS: Twenty-five white patients were genotyped for CYP2C19 by allele-specific polymerase chain reaction amplification, and their Helicobacter pylori status was assessed by serology and with immunoblot analysis. Intragastric pH was monitored over 24 hours, and meal-stimulated plasma gastrin concentration was measured over 4 hours (AUC 4h) before (day 0) and during (day 8) treatment with 20 mg omeprazole once daily. RESULTS: Eleven patients were homozygous for the wild-type allele (wt/wt), 12 were heterozygous EMs (wt/mut), and 2 were PMs (mut/mut). Median (95% confidence interval) 24-hour intragastric pH in the heterozygous EM group was 5.5 (range, 5.1-5. 9) compared with 3.1 (range, 2.7-3.6) in homozygous EMs (P < 0.0001) at day 8. The percentage of time with intragastric pH > 4 at day 8 was significantly higher in the wt/mut than wt/wt group (72.4% vs. 37.1%; P < 0.0001). H. pylori status had less influence than CYP2C19 on intragastric acidity. Omeprazole treatment increased meal-stimulated plasma gastrin concentrations from day 0 to day 8 in the homozygous EMs and heterozygous EMs by 16% (NS) and 157% (P = 0. 002), respectively. In heterozygous EMs, the gastrin increase was more pronounced in the H. pylori-positive group (226%) than H. pylori-negative group (80%; P = 0.02). CONCLUSIONS: The effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism in patients with acid-related disorders.

Plasma chromogranin A in patients with multiple endocrine neoplasia type 1.

Plasma chromogranin A (CgA) has been claimed to be a sensitive marker for neuroendocrine tumors, but its role in the early diagnosis of multiple endocrine neoplasia type 1 (MEN 1) pancreatic endocrine tumors has not been evaluated. We measured CgA in 36 patients with MEN 1, of whom 9 lacked pancreatic involvement, 20 had biochemical evidence of pancreatic endocrine tumors, and 7 displayed radiologically detectable pancreatic tumors. CgA was also analyzed in 25 patients with sporadic pancreatic endocrine tumors, 39 subjects with inflammatory bowel disease, 7 patients harboring nonendocrine pancreatic disease, and 19 healthy controls. Four of 9 of the MEN 1 patients without pancreatic involvement had elevated CgA. Furthermore, 60% with biochemically unequivocal tumors and all with a radiologically visible tumor showed elevations. All 25 patients with sporadic pancreatic endocrine tumor had increased CgA, as had 28% of patients with inflammatory bowel disease and 57% with nonendocrine pancreatic disease. Mean day to day CgA variation was 29% (range, 0-113%) in the neuroendocrine tumor patients and 21.0% (range, 0.0-47%, within reference range) among healthy controls. In summary, nonendocrine diseases may cause elevation of CgA, and its spontaneous variation can be considerable. Plasma chromogranin A is the most sensitive of the basal markers for neuroendocrine tumors, but cannot replace other established measures when screening for early pancreatic involvement in MEN 1.

Effect of CYP2C19 polymorphism on serum levels of vitamin B12 in patients on long-term omeprazole treatment.

BACKGROUND: The S-mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme, identified as CYP2C19, which catalyses the metabolism of omeprazole and some other drugs. AIM: To determine whether long-term treatment with omeprazole affects serum vitamin B12 levels, and if so to what extent it depends on CYP2C19 activity. METHODS: Serum vitamin B12 levels (pmol/L) were assessed in 179 patients. Genotyping for wild-type (wt) and mutated (mut) CYP2C19 alleles was performed by allele-specific PCR amplification. RESULTS: One-hundred and eleven of the patients received one dose of 20 mg omeprazole. No difference in B12 levels were found between heterozygous (wt/mut) (n = 23) and homozygous (wt/wt) (n = 85) patients (mean +/- s.d., 350 +/- 82 vs. 315 +/- 87 pmol/L, respectively). Three patients were mut/mut, with serum vitamin B12 levels of 303 +/- 50 pmol/L. In the 68 patients on long-term (>1 year) therapy with 20 mg omeprazole daily, serum vitamin B12 levels were lower in the heterozygous (wt/mut) (n = 19) compared to homozygous wt/wt (n = 49) (246 +/- 71 vs. 305 +/- 98 pmol/L, P = 0. 01, respectively). In one patient (mut/mut) who was studied both after a single dose and after long-term (15 months) treatment with omeprazole, serum vitamin B12 decreased from 360 to 178 pmol/L. In the wt/mut, but not in the wt/wt group, serum vitamin B12 levels were significantly lower in patients on long-term therapy compared with those receiving one dose (246 +/- 71 vs. 350 +/- 82 pmol/L, P < 0.0001, respectively). CONCLUSIONS: CYP2C19 polymorphism significantly affected serum vitamin B12 levels in patients on long-term therapy with omeprazole. In the future, genotyping of CYP2C19 may be useful for patients in need of long-term treatment with omeprazole or other proton pump inhibitors.

Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings, histology, age, and sex.

BACKGROUND: Our aim was to evaluate which specific factors are of importance for the gastroesophageal reflux seen in presumably healthy subjects. METHODS: We investigated 57 healthy, asymptomatic volunteers with computer-aided medical history interrogation, endoscopy, biopsy specimens from the distal esophagus, manometry, and 24-h ambulatory pH-monitoring. RESULTS: Eight subjects (14%) claimed intermittent reflux symptoms at the computer interview, but they did not have more acid reflux at pH-monitoring than asymptomatic volunteers. Thirteen subjects (23%) had abnormalities at endoscopy, 3 of whom had an erosion in the distal esophagus, and 12 had hiatus hernia. Subjects with hiatus hernia had increased acid reflux at 24-h pH-monitoring compared with those without hernia. If subjects with hernia were excluded, the degree of acid reflux was similar in all age groups. Men had more acid reflux than women, and these differences persisted if subjects with hernia were excluded. There was no correlation of histologic signs of esophagitis in the distal esophagus, lower esophageal sphincter pressure, smoking habit, or body mass index with reflux of acid to the esophagus. CONCLUSION: Hiatus hernia is a common finding in healthy subjects, and it predisposes to gastroesophageal acid reflux. Histologic abnormalities are poorly related to acid reflux in healthy volunteers. We found increased acid reflux in healthy men compared with women, but larger studies are needed to confirm these findings. Symptom evaluation is not sufficient to exclude significant gastroesophageal reflux in healthy volunteers, and we suggest that the possibility of esophageal abnormalities should be excluded by endoscopy in comparative studies of gastroesophageal reflux disease.

The sonde exam.

Sonde-type enteroscopy has made it possible to potentially examine the entire depths of the small intestine. A relatively high diagnostic yield has been obtained by the sonde method in patients with obscure gastrointestinal bleeding. These features have made sonde enteroscopy a clinically accepted method. However, sonde-type enteroscopy has also some disadvantages making it less then a perfect endoscopy method. This article focuses on the technical aspects of sonde enteroscopy, but also summarizes the indications and the outcome of clinical studies.

CYP2C19 genotype and phenotype determined with omeprazole in patients with acid-related disorders with and without Helicobacter pylori infection.

BACKGROUND: Omeprazole is to a major extent metabolized by cytochrome P450 isozyme CYP2C19. The aims of this study were to compare the phenotype of CYP2C19 determined by omeprazole with the genotype and to determine the effect of Helicobacter pylori infection on the metabolism of omeprazole. METHODS: One-hundred and forty-three Caucasian patients with acid-related disorders assessed with a combination of gastrointestinal symptoms and upper endoscopic findings were given 20 mg omeprazole orally. Three hours after intake, omeprazole and 5-hydroxyomeprazole plasma concentrations were determined with high-performance liquid chromatography, and the phenotype for metabolic capacity was expressed as metabolic ratio (MR). Genotyping of defect alleles (CYP2C19*2 and *3) was performed by polymerase chain reaction amplification. One hundred eleven patients were tested after the first dose of omeprazole and 32 patients after repetitive administration (median time, 30 days). H. pylori serology was determined with enzyme-linked immunosorbent assay at the time of phenotyping. RESULTS: Genotypically, 2.8% had two mutated alleles and were poor metabolizers (PM), and 22.4% were heterozygous extensive metabolizers (EM). Among the 111 patients who received the first omeprazole dose, 4 patients had MR >5--that is, belonged to the PM phenotype. Two of these had PM genotype (both CYP2C19*2/*2), and two had an EM genotype (CYP2C19*11*1 and *1/*3), indicating that they have still unidentified mutations. In the heterozygous EM group the mean MR was higher in patients who had been on continued omeprazole treatment than in those given the first dose (5.7 versus 2.5, P = 0.02). There were no significant differences in MR and omeprazole concentrations between H. pylori-negative (43%) and -positive (57%) patients. CONCLUSION: In all but two patients with probable unidentified mutations there was agreement between the CYP2C19 phenotype determined by omeprazole and the genotype. The metabolism of omeprazole in patients with acid-related disorders is genetically determined and without relation to H. pylori infection.

The value of different detection methods of Helicobacter pylori during treatment.

It has been suggested that profound acid inhibition by proton pump inhibitors affects the accuracy of H. pylori detection. This report aims to evaluate H. pylori status during treatment with four different invasive detection methods and to investigate if histopathological alterations during treatment can be used as an early marker for H. pylori eradication. Twenty-eight H. pylori-positive patients were studied randomized into two treatment groups: 14 patients received omeprazole, 20 mg plus amoxicillin 1,000 mg b.i.d (OA), and 14 patients received omeprazole, 20 mg and placebo b.i.d (OP) for 14 days. Biopsies from antrum and corpus of the stomach were collected on days 0, 10 and 42. H. pylori status was based on rapid urease test, cultivation, histology, and polymerase chain reaction (PCR). The biopsies were also graded according to the Sidney classification. In the OP and the OA group, 17% (2/12) and 92% (12/13) of the patients were H. pylori negative when tested during treatment (day 10). Four weeks after treatment none of the patients (0%) in the OP group and 61% (8/13) in the OA group had their H. pylori infection eradicated. PCR was up to 34% more sensitive than the other tests to detect H. pylori during treatment. There was a decrease in histological inflammation and activity in the antrum already during treatment in the OA group, but the decrease did not discriminate for successful treatment. During treatment with omeprazole alone or in combination with amoxicillin, H. pylori detection is impaired regardless of the detection method used. However, PCR appears to be more sensitive than other tests. Early changes in the histological appearance of the gastric mucosa do not predict H. pylori treatment outcome.

H. pylori stimulates gastrin release from canine antral cells in primary culture.

Patients chronically infected with Helicobacter pylori are known to have hypergastrinemia. Previous studies have demonstrated the stimulation of gastrin from isolated G cells by monocytes and cytokines. The aim of this study was to determine if H. pylori can directly stimulate gastrin secretion. The secretion of gastrin from canine G cells in 48-h primary cultures was investigated using either live H. pylori bacteria or various bacterial extracts from three well-characterized strains. Whole bacterial sonic extracts and water-extracted surface proteins, but not PBS extracts, from strains 43579 (CagA+/VacA+), 60190 (CagA+/VacA+), and 60190:v1 (CagA+/VacA-) significantly stimulated gastrin release. Controls demonstrated that gastrin stimulation by the sonic extracts was not due to a direct toxic effect on G cells. We conclude that H. pylori produces a soluble factor(s), which can directly stimulate gastrin release in enriched canine G cell cultures. This stimulatory effect may play an important role in the H. pylori-associated hypergastrinemia and subsequent development of peptic ulcer disease.

Symptom criteria do not distinguish between functional and organic dyspepsia.

DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden. OBJECTIVE: To find out if various diagnostic criteria could distinguish organic from non-organic causes of dyspepsia. SUBJECTS: 635 patients previously interviewed by computer questionnaire. INTERVENTIONS: Upper gastrointestinal endoscopy, laboratory tests, clinical examination. MAIN OUTCOME MEASURE: Differentiation between organic and functional dyspepsia. RESULTS: 106 patients had functional dyspepsia. Of these 83 had ulcer-like dyspepsia, 76 motility-like dyspepsia, and 50 reflux-like dyspepsia. Eight patients had unspecified dyspepsia. CONCLUSIONS: There was a considerable overlap between different subgroups, and the criteria did not differentiate between organic and non-organic causes of dyspepsia though the symptom criteria in most cases showed an independent value in discriminating between different subgroups. The clinical usefulness of the criteria remains to be shown.

Prolonged and profound acid inhibition is crucial in Helicobacter pylori treatment with a proton pump inhibitor combined with amoxicillin.

BACKGROUND: The aim was to investigate whether intragastric pH, meal-stimulated gastrin release, or demographic factors predict the outcome of Helicobacter pylori treatment. METHODS: Thirty-six patients with H. pylori infection were investigated with 24-h intragastric pH registration and meal-stimulated gastrin release before and during treatment with 20 mg omeprazole twice daily and 750 mg amoxicillin twice daily for 14 days. The influence of age, sex, smoking, ethnic origin, pH, and gastrin on treatment outcome were analysed with logistic regression. RESULTS: Eradication of H. pylori was achieved in 18 of 34 (53%) patients. The univariate analysis showed that age, ethnic origin, more than 84.2% of the time with pH above 4, and continuous periods longer than 156 min with intragastric pH above 6 were significantly associated with successful treatment of H. pylori. In the multivariate analysis only the two pH variables were found to be independent factors for predicting treatment outcome. CONCLUSION: The outcome of H. pylori treatment with omeprazole and amoxicillin may depend on several factors, such as age, ethnic origin, and a pronounced acid suppression. However, the only factor of independent importance in this study was prolonged and profound acid inhibition.

Comparison of the effect of lansoprazole and omeprazole on intragastric acidity and gastroesophageal reflux in patients with gastroesophageal reflux disease.

BACKGROUND: Lansoprazole (LAN) and omeprazole (OME) heal esophagitis effectively and to similar extents, but LAN has a faster effect on the relief of symptoms of gastroesophageal reflux. However, no strict comparison of the two proton pump inhibitors' effect on acid reflux and gastric acidity has been published. The aim of this study was to compare the effects of LAN and OME on gastroesophageal reflux with simultaneous measurements of gastric acidity in patients with established gastroesophageal reflux disease (GERD) and esophagitis. METHODS: Fourteen patients with endoscopically verified erosive esophagitis and with a pretreatment esophageal 24-h pH measurement showing acid reflux to the esophagus participated in the study. This was a double-blind, randomized study with crossover design. Before (day 0) and on the last day (day 5) of each treatment period with encapsulated 30 mg LAN or 20 mg OME daily, 24-h intraesophageal and intragastric acidity were measured with antimony electrodes connected to an ambulatory pH recording system. RESULTS: Ten of 14 patients completed the study. There were no differences in intragastric or intraesophageal acidity or the number of reflux episodes on day 0 between the two treatments. Both LAN and OME treatments increased the median and nocturnal intragastric pH and decreased the 24-h area under the time curve for intragastric acidity significantly and to about the same extent (79% and 69% acid inhibition by LAN and OME, respectively) (NS). However, the percentage of time with pH below 4 in the esophagus was significantly less during LAN treatment (1.92% +/- 2.29; mean +/- standard deviation) than during OME treatment (4.76% +/- 2.88%) on day 5 (P = 0.002). There were also significantly fewer reflux episodes >5 min during treatment with LAN (1.00 +/- 1.33) than with OME (2.90 +/- 2.42) at the end of the treatment period (P = 0.031). CONCLUSIONS: In this study lansoprazole and omeprazole had a comparable effect on gastric acidity in patients with established GERD with esophagitis. However, 30 mg lansoprazole daily reduced the acidity in the oesophagus and the number of refluxes more effectively than 20 mg omeprazole daily. This might indicate that proton pump inhibitors affect the esophageal clearance and/or influence the lower esophageal sphincter differently.

Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal pathways.

Isolated canine G cells in primary culture have been used to study calcium, protein kinase C (PKC), and rho/cytoskeletal-dependent intracellular pathways involved in bombesin- stimulated gastrin release. A method to obtain highly purified G cells by culture (64% G cells) after flow cytometry on elutriated fractions of cells from digested canine gastric antral mucosa has been developed. Pretreatment of G cells with thapsigargin (10(-8)-10(-6) M) and release experiments in Ca2+-containing or -depleted media showed that influx of Ca2+ into the cells and not acute release from intracellular stores plays an important role in bombesin-stimulated gastrin release. Inhibition of PKC by the specific inhibitor GF 109 203X did not affect bombesin-stimulated release. Rho, a small GTP-binding protein that regulates the actin cytoskeleton, is specifically antagonized by Clostridium botulinum C3 exoenzyme. C3 (10 microg/ml) enhanced basal and bombesin-stimulated gastrin release by 315 and 266%, respectively. The importance of the cytoskeleton for regulation of gastrin release was emphasized by a more pronounced release of gastrin when the organization of the actin cytoskeleton was disrupted by cytochalasin D (5 x 10(-)7 and 10(-)6 M). Wortmannin, a potent inhibitor of phosphoinositide-3-kinase, did not alter bombesin-stimulated gastrin release. Thus, it is concluded that bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by PKC, and is enhanced by disruption of rho/cytoskeletal pathways.

Twenty-four-hour basal and repetitive pentagastrin-stimulated gastric acid secretion in normal and sham-operated rats and in rats after gonadectomy or treatment with estradiol or testosterone.

BACKGROUND: Studies in different species have suggested, but not established, that sex hormones influence gastric acid secretion. We studied how acid output is affected by the sex hormones estradiol or testosterone in vivo and in vitro. METHODS: In gastric fistula rats that were normal, sham-operated, neonatally gonadectomized, or treated with estradiol or testosterone, 24-h basal and pentagastrin-stimulated acid secretion was measured. The in vitro effects of estradiol and testosterone on histamine-induced aminopyrine accumulation in isolated parietal cells were also determined. RESULTS: Basal acid output was similar in the two sexes, but stimulated secretion was significantly higher (34%; P < 0.01) in males. Ovariectomy did not influence acid output, whereas orchidectomy reduced basal (18%; NS) and stimulated 24-h secretion (P < 0.01). Estradiol decreased (23%; NS) the 24-h basal output in females but not in males. Estradiol suppressed stimulated secretion in females (29%, P < 0.01) and males (42%, P < 0.01) during the day. At night the stimulated secretion increased in both females (17%, NS) and males (32%, P < 0.05). A similar pattern was found when rats were treated with testosterone. In vitro, estradiol and testosterone reduced histamine-stimulated aminopyrine accumulation in both female and male isolated parietal cells. CONCLUSIONS: Estradiol and testosterone both appear to influence gastric secretion in rats, and their action differs between day and night, between the sexes, and between basal and stimulated secretion.

First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells.

Cholecystokinin (CCK)-A and CCK-B receptors are highly homologous members of the seven transmembrane domain G-protein-coupled receptor superfamily. Genes of both receptors contain five exons and share a similar exon-intron organization. To determine the structural basis of CCK-A receptor (CCK-AR) functionally coupled to Gs, a series of chimeric mutants were constructed by replacing exons of human CCK-B receptor (CCK-BR), from the second to the fifth (last) exon, with human CCK-AR counterparts. Binding and signal transduction properties of wild-type and chimeric receptors were examined in stably transfected HEK-293 cells. Chimeric receptors that maintained high affinity binding to CCK exhibited dose-dependent increases in intracellular calcium mobilization similar to both wild-type receptors. However, only the wild-type CCK-AR and chimeric mutants containing the second exon of CCK-AR were able to mediate significantly greater increases in intracellular cAMP content and adenylyl cyclase activity compared with wild-type CCK-BR. A CCK-BR mutant was further constructed by replacing five amino acids, Gly-Leu-Ser-Arg-(Arg)-Leu, in the first intracellular loop with the corresponding five CCK-AR specific amino acids, Ile-Arg-Asn-Lys-(Arg)-Met. The resultant receptor maintained high affinity binding to both CCK and gastrin and dose-dependent calcium responses similar to wild-type CCK-BR. However, this first intracellular loop mutant also gained positive cAMP responses to both sulfated CCK-8 and gastrin-17 with EC50 values of 8.5 +/- 1 nM and 23 +/- 7 nM, respectively. These data suggest that the first intracellular loop of CCK-AR is essential for coupling to Gs and activation of adenylyl cyclase signal transduction cascade.

Accurate detection of Helicobacter pylori infection with a simplified 13C urea breath test.

The urea breath test (UBT) has been shown to be a reliable non-invasive method for detection of H. pylori infection. There is widespread use of a test meal in the 13C UBT, but to what extent exclusion of the test meal actually influences the accuracy of the test has been poorly investigated. In addition, there is variability between test protocols in breath sampling frequency. In this evaluation, 91 patients with dyspeptic symptoms were investigated in an out-patient endoscopy ward, using a simplified 13C UBT without a test meal, and a single point breath evaluation after ingestion of 13C-labelled urea. Helicobacter pylori infection was diagnosed on upper endoscopy by histology and rapid urease tests on biopsies from the antrum and corpus mucosa of the stomach. Fifty-four percent of the patients had H. pylori infection. With the chosen cut-off level, the sensitivity and specificity of the 13C UBT were 92% and 95%, respectively. We conclude that this simplified 13C UBT is easy to perform and a very reliable test for detecting H. pylori infection, making it a suitable test in routine clinical work.

Effects of omeprazole and amoxycillin on the human oral and gastrointestinal microflora in patients with Helicobacter pylori infection.

Fourteen patients with Helicobacter pylori infection were treated with omeprazole capsules 20 mg and amoxycillin capsules 1000 mg twice daily for 14 days and 14 patients with omeprazole capsules 20 mg and placebo twice daily for 14 days. Samples from saliva, dental plaque and faeces and biopsies from antrum and corpus were analysed in order to determine the ecological changes in the normal microflora. Several microorganisms were affected by both treatment regimens. Two patients were colonised with enterobacteria in the oral cavity and stomach during the omeprazole plus amoxycillin treatment. A general increase in the number of microorganisms from gastric mucosa was observed in both treatment groups. A selection of resistant enterobacteria and an increase in beta-lactamase production was observed in the faecal samples during the omeprazole plus amoxycillin treatment. Eradication of H. pylori in the omeprazole-amoxycillin group was 50% and in the omeprazole placebo group 0% four weeks after treatment. No viable H. pylori were cultivated in the saliva, dental plaque or faecal samples. Treatment with omeprazole 20 mg and amoxycillin 1000 mg twice daily for 14 days altered the normal microflora in the oral, gastric and intestinal tract and antibiotic resistant microorganisms increased in numbers in the intestinal microflora.

Adenocarcinoid of the liver arising within an area of hamartoma with predominant bile duct component.

Malignant transformation in bile duct hamartomas has been previously reported in very rare instances. Here, we describe a unique case of a neuroendocrine tumor of the liver arising within an area of unusually large hamartoma with predominant bile duct component, hitherto unreported and distinct from the conventional von Meyenburg complex. The tumor was apparently secreting gastrin and chromogranin, with associated gastrinoma syndrome over several years. The histologic picture was reminiscent of a moderately differentiated adenocarcinoid, with positive mucin staining in a signet ring pattern. Tumor cells showed positive staining for neuron-specific enolase, chromogranin A, gastrin, and serotonin. Staining for pancreatic hormone peptides was negative. Resection of the tumor was apparently curative, with complete resolution of the patient's symptoms.