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Biomedical subjects

H Mieno

Publications and source records attributed to H Mieno.

At least 19 recordsLinked to original sources

Acid-suppressive effects of generic omeprazole: comparison of three brands of generic omeprazole with original omeprazole.

BACKGROUND: Generic omeprazole contains the same active ingredient as original omeprazole and require verification of the bioequivalence with original omeprazole. However, very few clinical studies have been reported. AIMS: A prospective, randomised, open-label, crossover study to compare acid-suppressive effect of generic omeprazole with that of original omeprazole. SUBJECTS: Seven healthy Helicobacter pylori-negative subjects of CYP2C19 extensive metaboliser. METHODS: Intragastric pH was measured for 24 h without medications (placebo) and on day 7 of repeated administration of 10 mg once daily after breakfast of original omeprazole, Omeprazon, or three brands of generic omeprazole, Omeprazole-Towa, Ovulanze or Omerap. RESULTS: Median values of intragastric pH and percentages of time with pH>4 for 24 h were significantly higher with administration of any omeprazole formulation compared with placebo (P<0.05, Wilcoxon signed-rank test). Whereas, during the night-time period (20:00-08:00 h), percentages of time with pH>4 with Omeprazole-Towa and Omerap were not significantly higher than placebo. Compared with Omeprazon, these two parameters for 24 h showed significantly greater inter-subject variations with Omeprazole-Towa (P<0.05 and P<0.01, F-test) and Ovulanze (P<0.05). CONCLUSIONS: Acid-suppressive effects of some brands of generic omeprazole are not the same as original omeprazole. These differences might be reflected in clinical outcomes.

Adult↗

Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2-receptor antagonist.

BACKGROUND: Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression. AIM: To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes. METHODS: Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h. RESULTS: With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH > 4 holding time ratios between poor metabolizers (PMs, n = 6) and the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg approximately lafutidine 20 mg > omeprazole 10 mg in homo-EMs, omeprazole 20 mg > omeprazole 10 mg approximately lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg approximately omeprazole 10 mg > lafutidine 20 mg in PMs. CONCLUSIONS: Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.

Acetamides↗

Adenocarcinoma complicating Barrett's esophagus: an analysis of cell proliferation.

In Japan, cases of Barrett's esophagus with concurrent adenocarcinoma are relatively rare. We report herein a case of long-segment Barrett's esophagus-associated adenocarcinoma in a 72-year-old Japanese man. The surgical specimen showed that an ulcerating tumor, measuring 5.5 x 3.9 cm, was present in the lower esophagus adjacent to the esophagogastric junction, the background lower esophagus having an erythematous appearance. Histologically, the ulcerating tumor was a well-to-moderately differentiated tubular adenocarcinoma, with a small area of signet ring cell carcinoma invading the adventitia. In addition, the esophageal epithelium was replaced by columnar epithelium (9.5 cm in length) with multifocal dysplastic changes. Immunohistochemically, the number of Ki-67-positive cells gradually increased, moving from the normal gastric mucosa (mean Ki-67 labeling index [mKLI], 2.6%) through Barrett's epithelium (mKLI, 12.9%), low-grade dysplasia (mKLI, 16.9%), and high-grade dysplasia (mKLI. 23.7%) to invasive carcinoma, in that order, with labeling higher in the invasive tubular adenocarcinoma elements (mKLI, 40.5%) than in areas of signet ring cell carcinoma (mKLI, 20.4%). Findings in our patient suggest that increased cellular proliferation plays an integral part, in the progression of Barrett's metaplasia to adenocarcinoma. The collection of further cases for analysis will be necessary to confirm this hypothesis.

Adenocarcinoma↗

Nonselective cation channel as a Ca(2+) influx pathway in pepsinogen-secreting cells of bullfrog esophagus.

In pepsinogen-secreting cells of bullfrog (Rana catesbeiana), recent evidence suggests that Ca(2+) release from internal stores followed by Ca(2+) influx across the plasma membrane elicits pepsinogen secretion. Such a Ca(2+) influx could be carried by a background current, potentiated by bombesin, that was found in these cells using the whole cell patch-clamp technique. The permeability ratio of Cs(+)-Rb(+)-K(+)-Na(+)-Li(+)-N-methyl-D-glucamine(+)-Ca(2+) was 1.01:1:1:0.86:0.72:0.54:0.34. The current was almost totally blocked by the nonselective cation channel blockers La(3+) (0.1 mM) and Gd(3+) (0.1 mM) and was activated by intracellular Ca(2+). These properties demonstrated that the current, which was activated by bombesin, was a nonselective cation current. At the same time, Gd(3+) suppressed pepsinogen secretion by 29 +/- 5.6% in isolated pepsinogen-secreting glands. These results are in accord with the idea that a nonselective cation channel in pepsinogen-secreting cells plays a role as a Ca(2+) influx pathway leading to secretion of pepsinogen in bullfrog esophageal mucosa.

Animals↗

Gastrointestinal motility in patients with irritable bowel syndrome studied by using radiopaque markers.

BACKGROUND: Irritable bowel syndrome (IBS) has been identified as a physiologic abnormality, but no test has been established as a diagnostic standard for gastrointestinal dyskinesia in IBS patients. The aim of this study was to investigate gastrointestinal motility in patients with IBS by using radiopaque markers. METHODS: Gastrointestinal motility was studied in IBS patients (n = 72), constipation patients (n = 19), diarrhoea patients (n = 9), and healthy controls (n = 23). Using three types of radiopaque markers, analysis was performed to establish the transit time and a new indicator, the 'scattering index'. RESULTS: Transit times were not characteristic in IBS. The patients with IBS had significantly higher scattering indexes in the colon and total gut than the healthy controls and the patients with constipation and diarrhoea. The transit time and scattering index of the colon were linearly correlated in the healthy controls and the constipation and diarrhoea patients but were not correlated in the IBS patients. Using transit time and scattering index was a reliable means of evaluating gastrointestinal motility in IBS patients, with a sensitivity of 65% and a specificity of 96%. CONCLUSION: Three days' use of the radiopaque marker method was useful for providing an objective means of detecting gastrointestinal dysmotility in IBS patients.

Adolescent↗

Pepsinogen secretion: coupling of exocytosis visualized by video microscopy and [Ca2+]i in single cells.

Conventional in vitro studies of pepsinogen secretion have measured secretion into the bulk medium and have demonstrated the critical role of Ca2+ in the process. The present study was undertaken to obtain further details of the process of secretion and its relation to Ca2+ changes over very short time periods. The relation between Ca2+ mobilization and exocytosis in an isolated individual peptic cell of the bullfrog was investigated by a method to measure both intracellular Ca2+ ([Ca2+]i), using a fluorescent Ca2+ indicator, fura 2, and exocytosis from single cells using a video microscope analyzing system. Bombesin (3.2 x 10(-7) M) and bethanechol (3.2 x 10(-4) M) caused a rapid increase in [Ca2+]i (initial peak) and a corresponding high frequency of initial exocytosis. After the initial peak, [Ca2+]i was maintained at a somewhat elevated level over the baseline (sustained phase), with a corresponding low frequency of exocytosis. Both the sustained phase of elevated [Ca2+]i and the related exocytosis were eliminated by the depletion of extracellular Ca2+. Low concentrations of bombesin (3.2 x 10(-10) M) and bethanechol (3.2 x 10(-7) M) caused sustained low-amplitude Ca2+ oscillations with correspondingly low frequencies but also caused sustained exocytosis. These data show that 1) cellular response differs between high and low concentrations of stimulus, 2) there is a close relation between [Ca2+]i and exocytosis, 3) exocytosis follows elevation of [Ca2+]i by 14-45 s (n = 6), and 4) there is a significant positive correlation between the peak [Ca2+]i and the number of exocytoses.

Animals↗

Expression of bcl-2 protein in esophageal squamous cell carcinomas and its association with lymph node metastasis.

BACKGROUND: Recent studies on the role of bcl-2 in malignant tumors have suggested its prognostic significance. The goals of the current study were to determine any correlation between bcl-2 expression in esophageal squamous cell carcinoma and histopathology, lymph node metastasis, and clinical variables, and to assess its applicability as a parameter for prognosis. METHODS: Immunohistochemical staining for bcl-2 (clone 124) was performed on archival material from 105 esophageal squamous cell carcinomas. The results were compared among patient subgroups. RESULTS: bcl-2 was expressed in 58% of esophageal carcinomas, demonstrating positive correlations with a lack of keratinization and an early stage of disease. Lymph node metastasis was significantly less frequently observed in the subset of early stage carcinomas with bcl-2 staining. Univariate analysis revealed significantly longer disease free survival in patients with bcl-2 positive carcinomas than in those bcl-2 negative. bcl-2 expression did not have independent prognostic value in a multivariate survival analysis. CONCLUSIONS: bcl-2 is frequently expressed in esophageal carcinomas, and this expression is positively associated with nonkeratinization and an early stage, whereas it is negatively linked with lymph node metastasis and may indicate a favorable prognosis.

Carcinoma, Squamous Cell↗

Modulation of Ca2+-activated K+ channels by Mg2+ and ATP in frog oxyntic cells.

Ca2+-activated K+ channels in the basolateral plasma membrane of bullfrog oxynticopeptic cells are intimately involved in the regulation of acid secretion. Patch-clamp techniques were applied to study the regulating mechanism of these channels. In the excised inside-out configuration, intracellular Mg2+ decreased channel activity in a dose-dependent manner. In the absence of Mg2+, administration of adenosine 5'-trisphosphate (ATP) to the cytoplasmic side also inhibited channel activity. On the other hand, in the presence of Mg2+, addition of ATP markedly increased channel activity. At a fixed concentration of free Mg2+, the Mg-ATP complex caused channel activation and shifted the dose response relationship between channel activity and the intracellular Ca2+ concentration to the left. A nonhydrolysable ATP analogue, adenosine 5'-[beta,gamma-imido]triphosphate (AMP-PNP) adenylyl [beta,gamma-methylene]diphosphate (AMP-PCP), could not substitute for ATP in channel activation, but a hydrolysable ATP analogue, adenosine 5'-O-(3-thiotriphosphate) (ATP[gammaS]) could do so. Furthermore, application of alkaline phosphatase to the cytoplasmic side inhibited channel activity. These results demonstrate that Ca2+-activated K+ channels are regulated by Mg2+ and ATP, and suggest that a phosphorylation reaction may be involved in the regulation mechanism of these channels.

Adenosine Triphosphate↗

Intragastric pH in postlaparotomy patients--effects of cimetidine.

Intragastric pH was continuously monitored in 21 patients who underwent colorectal surgery. Monitoring was started before surgery, and was continued for two days after surgery. Intragastric pH tended to increase during surgery, compared with measurements obtained before and after surgery, but was not affected by the duration of anesthesia or of the surgical procedure, or surgical position. After surgery, patients were divided into two groups: the cimetidine group (10 patients) received intravenous cimetidine 200 mg 4 times a day, while the control group (11 patients) received no treatment. Postoperative intragastric pH was higher than 3.0 throughout the study in the cimetidine group, but was approximately 1.3 in the control group. Upper gastrointestinal bleeding occurred in 2 patients in the control group, with intragastric pH falling abruptly during the bleeding episode. To prevent post-operative upper gastrointestinal bleeding, in addition to the administration of H2-blockers or antacids, appropriate treatments in response to changes in intragastric pH are necessary. Continuous monitoring of intragastric pH in surgical patients is considered to be of clinical importance.

Aged↗

Laser therapy for early upper gastrointestinal carcinoma.

An invasive procedure generally is the first choice of therapy for the treatment of gastric cancer. The development of improved microimaging and innovative engineering, however, has established a new field of endoscopic laser therapy. This article discusses the use of high-power and low-power lasers in the treatment of early gastric cancer.

Carcinoma↗

Endoscopic treatment of gastric cancer.

We analyzed 445 cases of early gastric cancer to confirm which were associated with lymph-node metastases. Overall, gastric cancers less than 2 cm in size, without an ulcer or ulcer scar, or protuberant or mixed morphology could be expected to be free of lymph-node metastases. In these patients with early gastric cancer without lymph-node metastasis, local treatment using surgical endoscopy could effectively eradicate the disease. Laser irradiation was performed in 44 cases and mucosal resection in 18 cases. All early gastric cancers less than 2 cm in size, with the exception of those located in the prepylorus or high on the posterior wall of the body of the stomach were eradicated by laser irradiation. Mucosal resection was used to ablate cancers less than 1 cm in size and with the exception of 1 case, total clearance was obtained. We conclude that early gastric cancer without lymph-node metastases can be eradicated by surgical endoscopic treatment.

Gastroscopy↗

Clinical treatment of gastroduodenal bleeding.

Our present study was conducted by cooperation between Departments of Internal Medicine and surgery of a hospital, which was highly significant because the results were comprehensive without a bias toward either department. The present report describes whether or not emergency operations have decreased because of progress in various conservative hemostatic methods for hemorrhagic ulcer and short-term and long-term prognoses after conservative therapy. Compared with the first 8-year period, the number of patients treated by conservative therapy increased with a definite decrease in that of emergency operations in the latter 8-year period. As for the results of conservative treatment, the rate of short-term prognostic hemostasis was 81.3%. Of the long-term prognostic cases, ulcers recurred in 50%, accompanied by recurrent bleeding in 34.8%. These patients were again treated by conservative therapy, and hemostasis was successful in 95.7%. The mortality rate following conservative therapy was 13.7% in the first period and 11.0% in the latter period. The surgical mortality rate was 6.0% in the first period and 5.4% in the latter period. There was no surgical death among the patients undergoing palliative operation. Our therapeutic policy for hemorrhagic ulcer will be described based on these findings.

Emergencies↗

Electrical characteristics of inward-rectifying K+ channels in isolated bullfrog oxyntic cells.

The properties of K+ channels in the isolated oxyntic cells of the bullfrog (Rana catesbeiana) were investigated using the patch-clamp method. Two types of K+ channels on the basolateral membrane were identified on the basis of their electrophysiological and pharmacological properties. The K+ channel most frequently observed has a single-channel conductance of 61.0 +/- 2.9 pS (n = 10) and is activated by an increase in intracellular Ca2+. The other K+ channel has a single-channel conductance of 30.3 +/- 2.7 pS (n = 7), which is activated by adenosine 3',5'-cyclic monophosphate (cAMP). The physiological and pharmacological characteristics common to the two K+ channels are inward-going rectification with a high selectivity for K+ and indirect inhibition by omeprazole. The inward rectification is controlled by intracellular Mg2+ in such a way that the more Mg2+ is applied intracellularly, the more their inward-rectifying property is enhanced. The finding that bethanechol and cAMP increase the open probability of these K+ channels as well as activating the acid secretion indicates that there may be a relationship between these two processes in the oxyntic cells.

Animals↗

[Gastric acid response to graded dose of pentagastrin in duodenal ulcer].

To characterize gastric acid response and its age distribution in the patients with duodenal ulcer (DU), we conducted pentagastrin (PG) dose-response study and calculated maximal response (Vmax-c), half maximal dose of PG (Km-c), and the mean response to 0.22 microgram/kg/hr of PG as percent of highest observed response (SI). The mean values of basal secretion (BAO), Vmax-c, and SI in DU were significantly greater than those of normal subjects (N). The mean values of Km-c were significantly less than those of N. The greater BAO, Vmax-c, and SI, and less Km-c were observed in all age groups of DU. The results indicate that DU patients not only secrete more acid but also are more sensitive to stimulation by pentagastrin than N, and that the characteristics are common in all age groups of DU.

Adolescent↗